Clinical investigation has been a major component of my academic life for over 25 years. My research has focused on the epidemiology of ESRD and on clinical trials in acute and chronic kidney disease in children. As a pediatric nephrologist, I learned early the critical importance of collaborative research. I was the first pediatric nephrology representative to the NIH-NIDDK National CAPD Registry Advisory Committee in 1986 and served in a similar advisory role to the USRDS when it was established in 1988. I was a co-founder of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) in 1987 and continue to serve as Secretary of the NAPRTCS Board of Directors. The NAPRTCS is the largest and longest running multi-center study group in pediatric nephrology consisting of three registries (CKD, Dialysis, Transplant) that have enrolled over 17,000 patients from over 100 centers in four countries. My current participation in observational studies and clinical trials in pediatrics also includes the Prospective Pediatric CRRT Registry and the International Pediatric Peritonitis Registry. I now devote considerable time to mentoring junior faculty, fellows and other trainees. In 2006 I co-founded and continue to co-direct the Stanford Intensive Course in Clinical Research Study Design and Performance, a week-long immersion course for junior faculty and fellows that is given twice yearly. Since 2005 I have also been heavily involved in re-engineering the clinical and translational research enterprise at Stanford School of Medicine and now serve as Medical Director of Operations, Training and Compliance in Spectrum, Stanford’s Clinical and Translational Science Award.

Clinical Focus

  • Nephrology (Kidney), Pediatric
  • Pediatric Nephrology
  • Dialysis
  • Kidney Transplantation
  • Continuous Renal Replacement Therapies
  • Hypertension
  • Acute and Chronic Kidney Failure

Academic Appointments

Administrative Appointments

  • please see cv, multiple (1978 - 2008)

Honors & Awards

  • please see cv, multiple (1978-2007)

Professional Education

  • Medical Education: Baylor College of Medicine (1971) TX
  • Fellowship: Baylor College Pediatric Nephrology Fellowship (1978) TX
  • Residency: Baylor College of Medicine Pediatric Residency (1976) TX
  • Internship: Baylor College of Medicine Pediatric Residency (1972) TX
  • Board Recertification, American Board of Pediatrics, Pediatrics and Pediatric Nephrology (1986)
  • Board Certification: American Board of Pediatrics, Pediatrics (1979)
  • Board Certification: American Board of Pediatrics, Pediatric Nephrology (1979)
  • MD, Baylor College of Medicine (1971)
  • BA (cum laude), Rice University, Biology (1967)

Current Research and Scholarly Interests

Dialysis, kidney transplantation, continuous renal replacement therapy in pediatric patients; chronic kidney disease in pediatric patients.

2023-24 Courses

All Publications

  • Eculizumab hypersensitivity and desensitization in a toddler with atypical hemolytic uremic syndrome JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE Lo, R., Alexander, S., Moss, J., Siddiqi, A., Liu, A. 2019; 7 (7): 2409–10
  • Two infants with bilateral renal agenesis who were bridged by chronic peritoneal dialysis to kidney transplantation. Pediatric transplantation Sheldon, C. R., Kim, E. D., Chandra, P., Concepcion, W., Gallo, A., Su, S., Grimm, P. C., Alexander, S. R., Wong, C. J. 2019: e13532


    Bilateral renal agenesis is associated with severe oligohydramnios and was considered incompatible with postnatal life due to severe pulmonary hypoplasia. The use of renal replacement therapy was limited by significant morbidity and mortality associated with dialysis in very young infants with major pulmonary pathology. In the United States, there is a tremendous controversy about whether or not the use of prenatal amniotic fluid infusions provides a benefit to fetuses with bilateral renal agenesis. One of the critical issues identified is that there are, as yet, no children reported who had achieved long-term survival. Previous reports all indicated these children died shortly after birth or after unsuccessful peritoneal dialysis. We present two infants with a prenatal diagnosis of bilateral renal agenesis whose mothers elected to undergo prenatal amnioinfusions. One was born at 28weeks with a birthweight of 1230g and the other born at 34weeks with a birthweight of 1940g. We present the details of both cases, with initial management on chronic peritoneal dialysis, which started shortly after birth, as a bridge to living related kidney transplants.

    View details for DOI 10.1111/petr.13532

    View details for PubMedID 31259459

  • Eculizumab Hypersensitivity and Desensitization in a Toddler with Atypical Hemolytic Uremic Syndrome. The journal of allergy and clinical immunology. In practice Lo, R. n., Alexander, S. n., Moss, J. n., Siddiqi, A. n., Liu, A. n. 2019

    View details for PubMedID 30946976

  • Range and Heterogeneity of Outcomes in Randomized Trials of Pediatric Chronic Kidney Disease. journal of pediatrics Chong, L. S., Sautenet, B., Tong, A., Hanson, C. S., Samuel, S., Zappitelli, M., Dart, A., Furth, S., Eddy, A. A., Groothoff, J., Webb, N. J., Yap, H., Bockenhauer, D., Sinha, A., Alexander, S. I., Goldstein, S. L., Gipson, D. S., Raman, G., Craig, J. C. 2017


    To determine the range and heterogeneity of outcomes reported in randomized controlled trials of interventions for children with chronic kidney disease (CKD).The Cochrane Kidney and Transplant Specialized Register was searched to March 2016. Randomized trials involving children across all stages of CKD were selected. All outcome domains and measurements were extracted from included trials. The frequency and characteristics of the outcome domains and measures were evaluated.From 205 trials included, 6158 different measurements of 100 different outcome domains were reported, with a median of 22 domains per trial (IQR 13-41). Overall, 52 domains (52%) were surrogate, 38 (38%) were clinical, and 10 (10%) were patient-reported. The 5 most commonly reported domains were blood pressure (76 [37%] trials), relapse/remission (70 [34%]), kidney function (66 [32%]), infection (61 [30%]), and height/pubertal development (51 [25%]). Mortality (14%), cardiovascular disease (4%), and quality of life (1%) were reported infrequently. The 2 most frequently reported outcomes, blood pressure and relapse/remission, had 56 and 81 different outcome measures, respectively.The outcomes reported in clinical trials involving children with CKD are extremely heterogeneous and are most often surrogate outcomes, rather than clinical and patient-centered outcomes such as cardiovascular disease and quality of life. Efforts to ensure consistent reporting of outcomes that are important to patients and clinicians will improve the value of trials to guide clinical decision-making. In our study, non-English articles were excluded.

    View details for DOI 10.1016/j.jpeds.2017.03.034

    View details for PubMedID 28449820

  • CRIT-LINE: a noninvasive tool to monitor hemoglobin levels in pediatric hemodialysis patients PEDIATRIC NEPHROLOGY Garro, R., Sutherland, S., Bayes, L., Alexander, S., Wong, C. 2015; 30 (6): 991-998


    The national average for achieving the KDOQI-recommended hemoglobin (Hgb) target level of 11-12 g/dL is low with the current anemia management protocol of measuring Hgb levels every 2-4 weeks to guide intervention. The objective of this study was to correlate initial Hgb readings from the CRIT-LINE monitor with actual serum Hgb levels in pediatric patients on hemodialysis (HD).Data were collected from pediatric HD patients who had Hgb tests ordered for routine and/or clinical reasons. Hgb concentrations were read with the CRIT-LINE after 0.5 or 1 L of blood had been processed by HD in patients with a body weight of ≤20 or >20 kg, respectively. Ultrafiltration was kept at a minimum until the CRIT-LINE Hgb was read.In total, 217 Hgb readings from 23 HD patients were analyzed. Results showed a statistically significant correlation between CRIT-LINE readings and laboratory Hgb measurements (r = 0.94, p < 0.0001) using Pearson correlation coefficients for well-distributed data. The mean Hgb levels measured by CRIT-LINE and the laboratory were 11.12 ± 1.63 and 11.31 ± 1.69 g/dL, respectively.The CRIT-LINE monitor is an accurate instrument for monitoring Hgb levels in HD patients. Further studies will be needed to evaluate whether using CRIT-LINE Hgb levels to guide anemia management will improve the percentage of children with Hgb levels within target.

    View details for DOI 10.1007/s00467-014-2986-1

    View details for Web of Science ID 000353296700016

    View details for PubMedID 25854612

  • Research Participant-Centered Outcomes at NIH-Supported Clinical Research Centers CTS-CLINICAL AND TRANSLATIONAL SCIENCE Kost, R. G., Lee, L. N., Yessis, J. L., Wesley, R., Alfano, S., Alexander, S. R., Kassis, S. B., Cola, P., Dozier, A., Ford, D. E., Harris, P. A., Kim, E., Lee, S. C., O'Riordan, G., Roth, M., Schuff, K., Wasser, J., Henderson, D. K., Coller, B. S. 2014; 7 (6): 430-440


    Although research participation is essential for clinical investigation, few quantitative outcome measures exist to assess participants' experiences. To address this, we developed and deployed a survey at 15 NIH-supported clinical research centers to assess participant-centered outcomes; we report responses from 4,961 participants.Survey questions addressed core aspects of the research participants' experience, including their overall rating, motivation, trust, and informed consent. We describe participant characteristics, responses to individual questions, and correlations among responses.Respondents broadly represented the research population in sex, race, and ethnicity. Seventy-three percent awarded top ratings to their overall research experience and 94% reported no pressure to enroll. Top ratings correlated with feeling treated with respect, listened to, and having access to the research team (R(2) = 0.80-0.96). White participants trusted researchers more (88%) than did nonwhite participants collectively (80%; p < 0.0001). Many participants felt fully prepared by the informed consent process (67%) and wanted to receive research results (72%).Our survey demonstrates that a majority of participants at NIH-supported clinical research centers rate their research experience very positively and that participant-centered outcome measures identify actionable items for improvement of participant's experiences, research protections, and the conduct of clinical investigation.

    View details for DOI 10.1111/cts.12167

    View details for Web of Science ID 000346292600002

    View details for PubMedID 24842076

    View details for PubMedCentralID PMC4237675

  • The Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry: a critical appraisal PEDIATRIC NEPHROLOGY Sutherland, S. M., Goldstein, S. L., Alexander, S. R. 2014; 29 (11): 2069-2076


    Continuous renal replacement therapy (CRRT), which provides gradual, predictable clearance and fluid removal, is commonly used to manage acute kidney injury (AKI) and fluid overload in critically ill children. The Prospective Pediatric CRRT (ppCRRT) Registry, founded in 2001 and comprising 13 pediatric centers in the United States, represents the largest cohort of children receiving CRRT to date. Data from the ppCRRT has been used to describe pediatric CRRT demographics and epidemiology, improve technical aspects of CRRT provision for children, and identify novel or underappreciated risk factors affecting survival. Whereas the registry has successfully answered many questions, a number of questions remain unanswered and new ones have arisen. This article describes the ppCRRT Registry, including its major findings, the lessons learned, and the limitations inherent in its design. Additionally, using the registry as a framework, areas of future study are identified and potential methodologies examined.

    View details for DOI 10.1007/s00467-013-2594-5

    View details for Web of Science ID 000342457700002

  • The prospective pediatric continuous renal replacement therapy (ppCRRT) registry: a critical appraisal. Pediatric nephrology Sutherland, S. M., Goldstein, S. L., Alexander, S. R. 2014; 29 (11): 2069-2076


    Continuous renal replacement therapy (CRRT), which provides gradual, predictable clearance and fluid removal, is commonly used to manage acute kidney injury (AKI) and fluid overload in critically ill children. The Prospective Pediatric CRRT (ppCRRT) Registry, founded in 2001 and comprising 13 pediatric centers in the United States, represents the largest cohort of children receiving CRRT to date. Data from the ppCRRT has been used to describe pediatric CRRT demographics and epidemiology, improve technical aspects of CRRT provision for children, and identify novel or underappreciated risk factors affecting survival. Whereas the registry has successfully answered many questions, a number of questions remain unanswered and new ones have arisen. This article describes the ppCRRT Registry, including its major findings, the lessons learned, and the limitations inherent in its design. Additionally, using the registry as a framework, areas of future study are identified and potential methodologies examined.

    View details for DOI 10.1007/s00467-013-2594-5

    View details for PubMedID 23982708

  • Association between Maintenance Fluid Tonicity and Hospital-Acquired Hyponatremia. journal of pediatrics Carandang, F., Anglemyer, A., Longhurst, C. A., Krishnan, G., Alexander, S. R., Kahana, M., Sutherland, S. M. 2013; 163 (6): 1646-1651


    To evaluate whether the administration of hypotonic fluids compared with isotonic fluids is associated with a greater risk for hyponatremia in hospitalized children.Informatics-enabled cohort study of all hospitalizations at Lucile Packard Children's Hospital between April 2009 and March 2011. Extraction and analysis of electronic medical record data identified normonatremic hospitalized children who received either hypotonic or isotonic intravenous maintenance fluids upon admission. The primary exposure was the administration of hypotonic maintenance fluids, and the primary outcome was the development of hyponatremia (serum sodium <135 mEq/L).A total of 1048 normonatremic children received either hypotonic (n = 674) or isotonic (n = 374) maintenance fluids upon admission. Hyponatremia developed in 260 (38.6%) children who received hypotonic fluids and 104 (27.8%) of those who received isotonic fluids (unadjusted OR 1.63; 95% CI 1.24-2.15, P < .001). After we controlled for intergroup differences and potential confounders, patients receiving hypotonic fluids remained more likely to develop hyponatremia (aOR 1.37, 95% CI 1.03-1.84). Multivariable analysis identified additional factors associated with the development of hyponatremia, including surgical admission (aOR 1.44, 95% CI 1.09-1.91), cardiac admitting diagnosis (aOR 2.08, 95% CI 1.34-3.20), and hematology/oncology admitting diagnosis (aOR 2.37, 95% CI 1.74-3.25).Hyponatremia was common regardless of maintenance fluid tonicity; however, the administration of hypotonic maintenance fluids compared with isotonic fluids was associated with a greater risk of developing hospital-acquired hyponatremia. Additional clinical characteristics modified the hyponatremic effect of hypotonic fluid, and it is possible that optimal maintenance fluid therapy now requires a more individualized approach.

    View details for DOI 10.1016/j.jpeds.2013.07.020

    View details for PubMedID 23998517

  • AKI in Hospitalized Children: Epidemiology and Clinical Associations in a National Cohort. Clinical journal of the American Society of Nephrology Sutherland, S. M., Ji, J., Sheikhi, F. H., Widen, E., Tian, L., Alexander, S. R., Ling, X. B. 2013; 8 (10): 1661-1669


    Although AKI is common among hospitalized children, comprehensive epidemiologic data are lacking. This study characterizes pediatric AKI across the United States and identifies AKI risk factors using high-content/high-throughput analytic techniques.For the cross-sectional analysis of the 2009 Kids Inpatient Database, AKI events were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Demographics, incident rates, and outcome data were analyzed and reported for the entire AKI cohort as well as AKI subsets. Statistical learning methods were applied to the highly imbalanced dataset to derive AKI-related risk factors.Of 2,644,263 children, 10,322 children developed AKI (3.9/1000 admissions). Although 19% of the AKI cohort was ≤1 month old, the highest incidence was seen in children 15-18 years old (6.6/1000 admissions); 49% of the AKI cohort was white, but AKI incidence was higher among African Americans (4.5 versus 3.8/1000 admissions). In-hospital mortality among patients with AKI was 15.3% but higher among children ≤1 month old (31.3% versus 10.1%, P<0.001) and children requiring critical care (32.8% versus 9.4%, P<0.001) or dialysis (27.1% versus 14.2%, P<0.001). Shock (odds ratio, 2.15; 95% confidence interval, 1.95 to 2.36), septicemia (odds ratio, 1.37; 95% confidence interval, 1.32 to 1.43), intubation/mechanical ventilation (odds ratio, 1.2; 95% confidence interval, 1.16 to 1.25), circulatory disease (odds ratio, 1.47; 95% confidence interval, 1.32 to 1.65), cardiac congenital anomalies (odds ratio, 1.2; 95% confidence interval, 1.13 to 1.23), and extracorporeal support (odds ratio, 2.58; 95% confidence interval, 2.04 to 3.26) were associated with AKI.AKI occurs in 3.9/1000 at-risk US pediatric hospitalizations. Mortality is highest among neonates and children requiring critical care or dialysis. Identified risk factors suggest that AKI occurs in association with systemic/multiorgan disease more commonly than primary renal disease.

    View details for DOI 10.2215/CJN.00270113

    View details for PubMedID 23833312

  • Two-point normalized protein catabolic rate overestimates nPCR in pediatric hemodialysis patients PEDIATRIC NEPHROLOGY Srivaths, P. R., Sutherland, S., Alexander, S., Goldstein, S. L. 2013; 28 (5): 797-801


    Normalized protein catabolic rate (nPCR) calculation depends on estimating the urea generation between consecutive hemodialysis (HD) treatments. Two-point nPCR using blood urea nitrogen (BUN) before and after the same HD treatment has not been validated in pediatric patients, who typically receive a more intense HD dose than adults. This study aimed to compare nPCR calculated with a two-point vs. a three-point nPCR model in pediatric HD patients.Pediatric patients receiving HD at 2 units were enrolled. Three BUN measurements were obtained around a midweek HD treatment: one prior to HD (preBUN1), one 30 s after HD (30sBUN), and one prior to the subsequent HD (preBUN2). The two-point nPCR model was calculated using preBUN1 and 30sBUN and the three-point nPCR model was calculated using preBUN2 and 30sBUN.Seventy-six BUN sets from 35 patients were analyzed. Mean age was 16.4 ± 3.5 years. Mean dry weight was 51.4 ± 17.1 kg. Mean spKt/V was 1.54 ± 0.23. Mean preBUN2 was significantly lower than mean preBUN1 (60.2 ± 18.6 vs. 64.0 ± 18.9 mg/dl, p = 0.0001). nPCR obtained from the three-point model was significantly lower than nPCR obtained from the two-point model (1.07 ± 0.31 vs. 1.17 ± 0.31 g/kg/day, p = 0.00001). Seven of 76 (9.2 %) paired comparisons yielded three-point nPCR <1 vs. two-point nPCR >1.Our data show that in pediatric patients receiving HD, the ((1) two-point and three-point models lead to significantly different nPCRs, and (2) inaccurate protein intake assessment may result from reliance on a two-point model for nPCR estimates.

    View details for DOI 10.1007/s00467-012-2371-x

    View details for Web of Science ID 000316571400014

    View details for PubMedID 23212562

  • Continuous renal replacement therapy in children PEDIATRIC NEPHROLOGY Sutherland, S. M., Alexander, S. R. 2012; 27 (11): 2007-2016


    Over the past several decades, the epidemiology of acute kidney injury (AKI) in children has changed significantly. Pediatric patients with AKI frequently have co-morbid conditions, substantial fluid overload, and marked disease severity. At the same time, continuous renal replacement therapy (CRRT) has become the preferred modality for the management of these patients. This manuscript provides a state-of-the-art review of the technical aspects of pediatric CRRT and examines the most recent data regarding CRRT indications, timing of initiation, dosing, and outcomes in critically ill children.

    View details for DOI 10.1007/s00467-011-2080-x

    View details for Web of Science ID 000309342000002

    View details for PubMedID 22366896

  • Conversion From Tacrolimus/Mycophenolic Acid to Tacrolimus/Leflunomide to Treat Cutaneous Warts in a Series of Four Pediatric Renal Allograft Recipients TRANSPLANTATION Lieuko Nguyen, L., McClellan, R. B., Chaudhuri, A., Alexander, S. R., Chen, S. F., Concepcion, W., Grimm, P. 2012; 94 (5): 450-455


    The challenge of immunosuppression in pediatric renal transplantation is to balance preventing rejection while avoiding infectious complications. A dermatological complication of immunosuppression is viral warts, which cause significant disfigurement and increase the risk of skin malignancy.We present three pediatric and adolescent renal allograft recipients with multiple, recalcitrant verrucae vulgares lesions and one patient with molluscum contagiosum who were switched from mycophenolate mofetil to leflunomide. Teriflunomide metabolite levels were carefully maintained between 50,000 and 100,000 ng/mL to balance its immunosuppressive and antiviral properties. No adverse events requiring discontinuation of leflunomide were encountered.Switching from mycophenolate mofetil to leflunomide successfully cleared verrucae vulgares and molluscum lesions in all four renal transplant patients.The ability to minimize and even resolve warts can improve quality of life by reducing risk of skin malignancies and emotional distress in solid organ transplant patients. Leflunomide is a potential therapeutic option for posttransplantation patients with skin warts because it serves both as an adjunct to the immunosuppressive regimen and an antiviral agent.

    View details for DOI 10.1097/TP.0b013e318264351e

    View details for Web of Science ID 000308668000012

    View details for PubMedID 22960763

  • Nonrenal indications for continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group PEDIATRIC CRITICAL CARE MEDICINE Fleming, G. M., Walters, S., Goldstein, S. L., Alexander, S. R., Baum, M. A., Blowey, D. L., Bunchman, T. E., Chua, A. N., Fletcher, S. A., Flores, F. X., Fortenberry, J. D., Hackbarth, R., McBryde, K., Somers, M. J., Symons, J. M., Brophy, P. D. 2012; 13 (5): E299-E304


    Continuous renal replacement therapy is the most often implemented dialysis modality in the pediatric intensive care unit setting for patients with acute kidney injury. However, it also has a role in the management of patients with nonrenal indications such as clearance of drugs and intermediates of disordered cellular metabolism.Using data from the multicenter Prospective Pediatric Continuous Renal Replacement Therapy Registry, we report a cohort of pediatric patients receiving continuous renal replacement therapy for nonrenal indications. Nonrenal indications were obtained from the combination of "other" category for continuous renal replacement therapy initiation and patient diagnosis (both primary and secondary). This cohort was further divided into three subgroups: inborn errors of metabolism, drug toxicity, and tumor lysis syndrome.From 2000 to 2005, a total of 50 continuous renal replacement therapy events with nonrenal indications for therapy were included in the Prospective Pediatric Continuous Renal Replacement Therapy Registry. Indication-specific survival of the subgroups was 62% (inborn errors of metabolism), 82% (tumor lysis syndrome), and 95% (drug toxicity). The median small solute dose delivered among the subgroups ranged from 2125 to 8213 mL/1.73 m/hr, with 54%-59% receiving solely diffusion-based clearance as continuous venovenous hemodialysis. No association was established between survival and dose delivered, modality of continuous renal replacement therapy, or use of intermittent hemodialysis prior to continuous renal replacement therapy.Pediatric patients requiring continuous renal replacement therapy for nonrenal indications are a distinct cohort within the population receiving renal replacement therapy with little published experience of outcomes for this group. Survival within this cohort varies by indication for continuous renal replacement therapy and is not associated with continuous renal replacement therapy modality. Additionally, survival is not associated with small solute doses delivered within a cohort receiving >2000 mL/1.73 m/hr. Our data suggest metabolic control is established rapidly in pediatric patients and that acute detoxification may be provided with continuous renal replacement therapy for both the initial and maintenance phases of treatment using either convection or diffusion at appropriate doses.

    View details for DOI 10.1097/PCC.0b013e31824fbd76

    View details for Web of Science ID 000308537800005

    View details for PubMedID 22805158

  • Rituximab treatment for recurrence of nephrotic syndrome in a pediatric patient after renal transplantation for congenital nephrotic syndrome of Finnish type PEDIATRIC TRANSPLANTATION Chaudhuri, A., Kambham, N., Sutherland, S., Grimm, P., Alexander, S., Concepcion, W., Sarwal, M., Wong, C. 2012; 16 (5): E183-E187


    Congenital nephrotic syndrome (CNS) of the Finnish type due to mutation in the NPHS-1 gene results in massive proteinuria due to structural abnormality in the glomerular slit diaphragm, and is usually refractory to immunosuppressive therapy. Patients eventually require bilateral nephrectomy and renal replacement therapy, with transplantation being the ultimate goal. Post-transplant recurrence of nephrotic syndrome occurs in about 25% of children and is thought to be immune-mediated secondary to antibodies formed against the nephrin protein in renal allograft. Conventional therapy with calcineurin inhibitors (CNI), cyclophosphamide and corticosteroids with or without plasmapheresis often fails to achieve remission resulting in graft loss in 12-16%. There is limited experience with use of rituximab (RTX) in pediatric organ transplant recipients. We report the first case of post-transplant recurrence of nephrotic syndrome in a 4-yr-old child with CNS due to NPHS-1 mutation in whom CNI, corticosteroid and cyclophosphamide therapy was unsuccessful, but who achieved remission after depletion of B cells with RTX, associated with a decrease in the level of anti-nephrin antibodies. The child remains in remission 5 yr following treatment. Our experience suggests that activated B cells may play a pivotal role in the recurrence of nephrosis after renal transplantation in children with CNS.

    View details for DOI 10.1111/j.1399-3046.2011.01519.x

    View details for PubMedID 21672106

  • Tracking the impact of the National Institutes of Health Clinical and Translational Science Awards on child health research: developing and evaluating a measurement strategy PEDIATRIC RESEARCH Huskins, W. C., Sullivan, C. D., Wang, J., Aitken, M., Alexander, S. R., Epstein, L. G., Hoberman, A., Neufeld, E., Philipps, A., Shanley, T. P., Szilagyi, P., Purucker, M., Barkin, S. L. 2012; 71 (5): 619-624

    View details for DOI 10.1038/pr.2012.5

    View details for Web of Science ID 000303373300014

    View details for PubMedID 22398699

    View details for PubMedCentralID PMC3582389

  • Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss PEDIATRIC TRANSPLANTATION Sutherland, S. M., Chen, G., Sequeira, F. A., Lou, C. D., Alexander, S. R., Tyan, D. B. 2012; 16 (1): 12-17


    Long-term outcomes following renal transplantation remain disappointing. Recently, interest has focused on the antibody-mediated component of allograft injury and the deleterious effects of DSA. We applied a novel C1q solid-phase assay in parallel with the standard IgG SAB assay to identify DSA with the potential to activate complement by binding C1q. Among 193 consecutive renal transplants at our center, 19.2% developed de novo DSA following transplantation. Of the patients with DSA, 43% had antibodies that bound C1q in vitro [C1q+ DSA]. Patients with C1q+ DSA were more likely to develop allograft loss than patients with DSA that did not bind C1q (46.7% vs. 15%; p = 0.04); patients with C1q+ DSA were nearly six times more likely to lose their transplant than those with C1q- DSA. Additionally, patients with C1q+ DSA who underwent allograft biopsy were more likely to demonstrate C4d deposition (50% vs. 8%; p = 0.03) and meet criteria for acute rejection (60% vs. 17%; p = 0.02) when compared with patients with DSA that did not bind C1q. These data suggest that DSA with the ability to activate complement, as determined by this novel C1q assay, are associated with greater risk of acute rejection and allograft loss.

    View details for DOI 10.1111/j.1399-3046.2011.01599.x

    View details for Web of Science ID 000299154200010

    View details for PubMedID 22093755

  • End-Stage Renal Disease and Cardiomyopathy in Children: Cardiac Effects of Renal Transplantation TRANSPLANTATION Lal, A. K., de Biasi, A. R., Alexander, S., Rosenthal, D. N., Sutherland, S. M. 2012; 93 (2): 182-187


    The occurrence and progression of cardiomyopathy is well known in patients with end-stage renal disease (ESRD). However, the feasibility of renal transplantation in the setting of cardiac dysfunction and the effect of renal transplantation on this progression remain poorly studied in pediatric patients.A single-center, retrospective review of pediatric renal transplants between January 1, 2001, and December 31, 2010, was conducted. Six children with ESRD and severe systolic dysfunction underwent renal transplantation. Clinical data were collected and compared for the pretransplant, peritransplant, and posttransplant periods.Nutritional support, dialysis, and chronic kidney disease and heart failure therapy led to improved cardiac function before transplantation (ejection fraction 28.8%±9.6% vs. 44.4%±11.5%; fractional shortening 12.7%±5.1% vs. 23.6%±6.2%); however, normal systolic function was not achieved before transplantation in any patient. After transplantation, two patients had normalization of systolic function by hospital discharge, while the systolic function of the remaining four patients normalized during the first posttransplant year. Mean ejection fraction 1 year posttransplant was 22 units greater than before transplant. All patients experienced excellent allograft function in the peritransplant period. Mean estimated creatinine clearance 1 year posttransplant was 93.2±33.3 mL/min/1.73 m(2).Renal transplantation can be performed safely in children with ESRD and severe systolic dysfunction. After transplantation, systolic function continues to improve and may reach normal levels during the first posttransplant year. The presence of severe systolic dysfunction in pediatric dialysis patients should not deter referral for renal transplantation.

    View details for DOI 10.1097/TP.0b013e31823be7f8

    View details for PubMedID 22146314

  • Notes on the History of Dialysis Therapy in Children PEDIATRIC DIALYSIS, SECOND EDITION Alexander, S. R., Cochat, P., Warady, B. A., Schaefer, F., Alexander 2012: 3–16
  • Acute Kidney Injury: Diagnosis and Treatment with Peritoneal Dialysis, Hemodialysis, and CRRT PEDIATRIC DIALYSIS, SECOND EDITION Brophy, P. D., Yap, H., Alexander, S. R., Warady, B. A., Schaefer, F., Alexander 2012: 697–736
  • Dialyzing the Young DIALYSIS: HISTORY, DEVELOPMENT AND PROMISE Goldstein, S. L., Alexander, S. R., Ing, T. S., Rahman, M. A., Kjellstrand, C. M. 2012: 735–44
  • The Demographics of Dialysis in Children PEDIATRIC DIALYSIS, SECOND EDITION Fadrowski, J. J., Alexander, S. R., Warady, B. A., Warady, B. A., Schaefer, F., Alexander 2012: 37–51
  • End-Stage Renal Disease Due to Lupus Nephritis Among Children in the US, 1995-2006 ARTHRITIS AND RHEUMATISM Hiraki, L. T., Lu, B., Alexander, S. R., Shaykevich, T., Alarcon, G. S., Solomon, D. H., Winkelmayer, W. C., Costenbader, K. H. 2011; 63 (7): 1988-1997


    To identify predictors of wait-listing for kidney transplantation, kidney transplantation, and mortality among children with lupus nephritis-associated end-stage renal disease (ESRD).Children ages 5-18 years with new-onset lupus nephritis-associated ESRD were identified in the US Renal Data System (1995-2006). Demographic and clinical characteristics, causes of death, and predictors of wait-listing for kidney transplantation, kidney transplantation, and mortality during the first 5 years of ESRD were investigated. Cox proportional hazards models were used.A total of 583 children had incident lupus nephritis-associated ESRD. The mean ± SD age of the patients at the time of ESRD onset was 16.2 ± 2.4 years; 49% were African American, and 24% were Hispanic. During the 5-year period after the onset of ESRD, 292 (49%) were wait-listed, 193 (33%) received a kidney transplant, and 131 (22%) died. The main causes of death were cardiopulmonary (31%) and infectious (16%). Children living in the northeast and west were more than twice as likely as children in the south to be wait-listed and were >50% more likely than children in the south to undergo transplantation. There were fewer kidney transplants among older versus younger patients (odds ratio [OR] 0.59, P = 0.009), African American versus white patients (OR 0.48, P < 0.001), Hispanic versus non-Hispanic patients (OR 0.63, P = 0.03), and those with Medicaid versus those with private insurance (OR 0.70, P = 0.03). Mortality among African American children was almost double that among white children (OR 1.83, P < 0.001).Among US children with lupus nephritis-associated ESRD, age, race, ethnicity, type of medical insurance, and geographic region were associated with significant variation in 5-year wait-listing for kidney transplantation, kidney transplantation, and mortality.

    View details for DOI 10.1002/art.30350

    View details for Web of Science ID 000292809700027

    View details for PubMedID 21445963

    View details for PubMedCentralID PMC3128195

  • Role of Twenty-Four-Hour Ambulatory Blood Pressure Monitoring in Children on Dialysis CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Chaudhuri, A., Sutherland, S. M., Begin, B., Salsbery, K., McCabe, L., Potter, D., Alexander, S. R., Wong, C. J. 2011; 6 (4): 870-876


    Pre- or postdialysis BP recordings are imprecise, can be biased, and have poor test-retest reliability in children on dialysis. We aimed to examine the possible differences between pre- and postdialysis BP levels and 24-hour ambulatory BP monitoring (ABPM) in diagnosis of hypertension (HTN).Twenty-four children on dialysis had 24-hour ABPM in the interdialytic period, and values were compared with average pre- and postdialysis systolic BP (SBP) and diastolic BP (DBP) recordings that week. Each patient had an echocardiogram to determine presence of left ventricular hypertrophy (LVH).By ABPM, 8% of patients had white coat HTN and 12% had masked HTN. There was no significant difference in diagnosis of systolic HTN based on ABPM daytime SBP mean or load and postdialysis SBP. However, only 15% of patients had diastolic HTN based on postdialysis measures, whereas 46% of patients had significantly elevated daytime DBP loads and 71% had high nighttime DBP loads on ABPM. Forty-eight percent of patients were SBP nondippers. Children with LVH had higher daytime and nighttime SBP loads, significantly higher daytime and nighttime DBP loads, and lesser degree of nocturnal dipping of SBP compared with those who did not.ABPM is more informative than pre- and postdialysis BPs and improves the predictability of BP as a risk factor for target organ damage. Diagnosis and treatment monitoring of HTN among pediatric dialysis patients is enhanced with addition of ABPM.

    View details for DOI 10.2215/CJN.07960910

    View details for Web of Science ID 000289223600026

    View details for PubMedID 21273374

    View details for PubMedCentralID PMC3069381

  • Enterococcal peritonitis in children receiving chronic peritoneal dialysis NEPHROLOGY DIALYSIS TRANSPLANTATION Sutherland, S. M., Alexander, S. R., Feneberg, R., Schaefer, F., Warady, B. A. 2010; 25 (12): 4048-4054


    Peritonitis is a common complication of chronic peritoneal dialysis (CPD) and can be associated with technique failure. Enterococcus is an uncommon peritoneal pathogen in children receiving CPD but represents a potential therapeutic challenge due to its innate resistance to cephalosporins and emerging resistance to glycopeptides.The International Pediatric Peritonitis Registry is a global consortium of 47 paediatric dialysis centres designed to address validation of the International Society for Peritoneal Dialysis paediatric peritonitis treatment guidelines. Between 2001 and 2004, peritonitis episodes were assessed in 392 participating children receiving CPD.Among the 392 patients, 340 episodes of culture-positive peritonitis were evaluated. Twenty of these episodes were due to Enterococcus species (5.9%). There were no clinical characteristics uniquely associated with enterococcal peritonitis at presentation. After 3 days of therapy, 75% of patients were pain free, 95% had decreased effluent cloudiness and 90% were afebrile. Only one patient required a catheter exchange, and all patients experienced full functional recovery. Despite broad in vitro resistance to cephalosporins and 21% resistance to glycopeptides, neither in vitro resistance pattern nor choice of empiric antibiotic regimen affected short- or long-term outcomes.Enterococci are likely responsible for ∼6% of culture-positive peritonitis episodes in children receiving CPD. Although it was not possible to identify patients with enterococcal peritonitis based on presentation, clinical response was not associated with in vitro resistance patterns, and patients who initially received a cephalosporin-based empiric regimen until culture results are available are likely to respond quickly and have full functional recovery.

    View details for DOI 10.1093/ndt/gfq295

    View details for PubMedID 20501457

  • Relapsing Peritonitis in Children Who Undergo Chronic Peritoneal Dialysis: A Prospective Study of the International Pediatric Peritonitis Registry CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Lane, J. C., Warady, B. A., Feneberg, R., Majkowski, N. L., Watson, A. R., Fischbach, M., Kang, H. G., Bonzel, K. E., Simkova, E., Stefanidis, C. J., Klaus, G., Alexander, S. R., Ekim, M., Bilge, I., Schaefer, F. 2010; 5 (6): 1041-1046


    The International Pediatric Peritonitis Registry (IPPR) was established to collect prospective data regarding peritoneal dialysis (PD)-associated peritonitis in children. In this report, we present the IPPR results that pertain to relapsing peritonitis (RP).This was an online, prospective entry into the IPPR of data that pertain to peritonitis cases by participating centers.Of 490 episodes of nonfungal peritonitis, 52 (11%) were followed by a relapse. There was no significant difference between RP and non-RP in distribution of causative organisms and antibiotic sensitivities. Initial empiric therapy-ceftazidime with either first-generation cephalosporin or glycopeptide (vancomycin or teicoplanin)-was not associated with relapse. Switching to monotherapy with a first-generation cephalosporin on the basis of culture results was associated with higher relapse rate (23%) than other final antibiotic therapies (0 to 9%). Culture-negative RP was less likely to have a satisfactory early treatment response than non-RP (82 versus 98%). Young age, single-cuff catheter, downward-pointing exit site, and chronic systemic antibiotic prophylaxis were additional independent risk factors for RP in the multivariate analysis. Compared with non-RP, RP was associated with a lower rate of full functional recovery (73 versus 91%), higher ultrafiltration problems (14 versus 2%), and higher rate of permanent PD discontinuation (17 versus 7%).This is the largest multicenter, prospective study to date to examine RP in children. In addition, this is the first report in the literature to examine specifically the relationship of postempiric antibiotic treatment regimens to the subsequent risk for relapse.

    View details for DOI 10.2215/CJN.05150709

    View details for Web of Science ID 000278596200014

    View details for PubMedID 20430942

    View details for PubMedCentralID PMC2879316

  • Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy: The Prospective Pediatric Continuous Renal Replacement Therapy Registry AMERICAN JOURNAL OF KIDNEY DISEASES Sutherland, S. M., Zappitelli, M., Alexander, S. R., Chua, A. N., Brophy, P. D., Bunchman, T. E., Hackbarth, R., Somers, M. J., Baum, M., Symons, J. M., Flores, F. X., Benfield, M., Askenazi, D., Chand, D., Fortenberry, J. D., Mahan, J. D., McBryde, K., Blowey, D., Goldstein, S. L. 2010; 55 (2): 316-325


    Critically ill children with hemodynamic instability and acute kidney injury often develop fluid overload. Continuous renal replacement therapy (CRRT) has emerged as a favored modality in the management of such children. This study investigated the association between fluid overload and mortality in children receiving CRRT.Prospective observational study.297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry.Fluid overload from intensive care unit (ICU) admission to CRRT initiation, defined as a percentage equal to (fluid in [L] - fluid out [L])/(ICU admit weight [kg]) x 100%.The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness.153 patients (51.5%) developed < 10% fluid overload, 51 patients (17.2%) developed 10%-20% fluid overload, and 93 patients (31.3%) developed > or = 20% fluid overload. Patients who developed > or = 20% fluid overload at CRRT initiation had significantly higher mortality (61/93; 65.6%) than those who had 10%-20% fluid overload (22/51; 43.1%) and those with < 10% fluid overload (45/153; 29.4%). The association between degree of fluid overload and mortality remained after adjusting for intergroup differences and severity of illness. The adjusted mortality OR was 1.03 (95% CI, 1.01-1.05), suggesting a 3% increase in mortality for each 1% increase in severity of fluid overload. When fluid overload was dichotomized to > or = 20% and < 20%, patients with > or = 20% fluid overload had an adjusted mortality OR of 8.5 (95% CI, 2.8-25.7).This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality.Critically ill children who develop greater fluid overload before initiation of CRRT experience higher mortality than those with less fluid overload. Further goal-directed research is required to accurately define optimal fluid overload thresholds for initiation of CRRT.

    View details for DOI 10.1053/j.ajkd.2009.10.048

    View details for Web of Science ID 000274537000021

    View details for PubMedID 20042260

  • Steroid-Free Immunosuppression Since 1999: 129 Pediatric Renal Transplants with Sustained Graft and Patient Benefits AMERICAN JOURNAL OF TRANSPLANTATION Li, L., Chang, A., Naesens, M., Kambham, N., Waskerwitz, J., Martin, J., Wong, C., Alexander, S., Grimm, P., Concepcion, W., Salvatierra, O., Sarwal, M. M. 2009; 9 (6): 1362-1372


    Despite early promising patient and graft outcomes with steroid-free (SF) immunosuppression in pediatric kidney transplant recipients, data on long-term safety and efficacy results are lacking. We present our single-center experience with 129 consecutive pediatric kidney transplant recipients on SF immunosuppression, with a mean follow-up of 5 years. Outcomes are compared against a matched cohort of 57 concurrent recipients treated with steroid-based (SB) immunosuppression. In the SF group, 87% of kidney recipients with functioning grafts remain corticosteroid-free. Actual intent-to-treat SF (ITT-SF) and still-on-protocol SF patient survivals are 96% and 96%, respectively, actual graft survivals for both groups are 93% and 96%, respectively and actual death-censored graft survivals for both groups are 97% and 99%, respectively. Unprecedented catch-up growth is observed in SF recipients below 12 years of age. Continued low rates of acute rejection, posttransplant diabetes mellitus (PTDM), hypertension and hyperlipidemia are seen in SF patients, with sustained benefits for graft function. In conclusion, extended enrollment and longer experience with SF immunosuppression for renal transplantation in low-risk children confirms protocol safety, continued benefits for growth and graft function, low acute rejection rates and reduced cardiovascular morbidity.

    View details for DOI 10.1111/j.1600-6143.2009.02640.x

    View details for Web of Science ID 000266448900017

    View details for PubMedID 19459814

    View details for PubMedCentralID PMC2724986

  • Protein and calorie prescription for children and young adults receiving continuous renal replacement therapy: A report from the Prospective Pediatric Continuous Renal Replacement Therapy Registry Group CRITICAL CARE MEDICINE Zappitelli, M., Goldstein, S. L., Symons, J. M., Somers, M. J., Baum, M. A., Brophy, P. D., Blowey, D., Fortenberry, J. D., Chua, A. N., Flores, F. X., Benfield, M. R., Alexander, S. R., Askenazi, D., Hackbarth, R., Bunhman, T. E. 2008; 36 (12): 3239-3245


    Few published reports describe nutrition provision for critically ill children and young adults with acute kidney injury receiving continuous renal replacement therapy. The goals of this study were to describe feeding practices in pediatric continuous renal replacement therapy and to evaluate factors associated with over- and under-prescription of protein and calories.Retrospective database study.Multicenter study in pediatric critical care units.Patients with acute kidney injury (estimated glomerular filtration rate < 75 mL/min/1.73 m at continuous renal replacement therapy initiation) enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy Registry.None.Nutrition variables: initial and maximal protein (g/kg/day) and caloric (kcal/kg/day) prescription and predicted resting energy expenditure (kcal/kg/day). We determined factors predicting initial and maximal protein and caloric prescription by multivariate analysis.One hundred ninety-five patients (median [interquartile range] age = 8.1 [12.8] yrs, 56.9% men) were studied. Mean protein and caloric prescriptions at continuous renal replacement therapy initiation were 1.3 +/- 1.5 g/kg/day (median, 1.0; range, 0-10) and 37 +/- 27 kcal/kg/day (median, 32; range, 0-107). Mean maximal protein and caloric prescriptions during continuous renal replacement therapy were 2.0 +/- 1.5 g/kg/day (median, 1.7; range, 0-12) and 48 +/- 32 kcal/kg/day (median, 43; range, 0-117). Thirty-four percent of patients were initially prescribed < 1 g/kg/day protein; 23% never attained > 1 g/kg/day protein prescription. By continuous renal replacement therapy day 5, median protein prescribed was > 2 g/kg/day. Protein prescription practices differed substantially between medical centers with 5 of 10 centers achieving maximal protein prescription of > 2 g/kg/day in > or = 40% of patients. Caloric prescription exceeded predicted resting energy expenditure by 30%-100%. Factors independently associated with maximal protein and caloric prescription while on continuous renal replacement therapy were younger age, initial protein and caloric prescription and number of continuous renal replacement therapy treatment days (p < 0.05).Protein prescription in pediatric continuous renal replacement therapy may be inadequate. Inter-center variation exists with respect to nutrition prescription. Feeding practice standardization and research in pediatric acute kidney injury nutrition are essential to begin providing evidence-based feeding recommendations.

    View details for DOI 10.1097/CCM.0b013e31818f3f40

    View details for Web of Science ID 000261213500016

    View details for PubMedID 18936697

  • Combined liver-kidney transplantation in children: Indications and outcome PEDIATRIC TRANSPLANTATION Sutherland, S. M., Alexander, S. R., Sarwal, M. M., Berquist, W. E., Concepcion, W. 2008; 12 (8): 835-846


    Although it remains a relatively infrequent procedure in children, CLKT has become a viable option for a select group of pediatric patients with severe liver and kidney disease. Most are performed for rare primary diseases such as PH1, but a selected few are performed in the setting of concomitant hepatic and renal failure of uncertain etiology and prognosis. This article reviews the indications for and outcomes following CLKT in children. While it focuses on the specific primary diseases which impact liver and kidney function simultaneously, it addresses the indications based on concomitant hepatic and renal failure, such as seen in the hepatorenal syndrome, as well.

    View details for DOI 10.1111/j.1399-3046.2008.01041.x

    View details for Web of Science ID 000260341600004

    View details for PubMedID 19000066

  • Acute kidney injury in pediatric stem cell transplant recipients SEMINARS IN NEPHROLOGY DiCarlo, J., Alexander, S. R. 2008; 28 (5): 481-487


    Because respiratory dysfunction after hematopoietic stem cell transplantation is a manifestation of a continuum of dysfunction temporarily induced by the transplant process, a proactive rather than reactive approach might prevent or attenuate its progression to acute respiratory distress syndrome. Organ dysfunction in this population results from cytokine-driven processes, of which the first manifestation includes fluid accumulation. We describe a multistep protocol that first targets fluid balance control, both through restriction of intake and through augmentation of output using dopamine and furosemide infusions. If these steps fail to stem the tide of water accumulation, we advocate the relatively early use of continuous renal replacement therapy, its use triggered by a continued increase in body weight (>10% above baseline), an increasing c-reactive protein level, and an increasing oxygen need. Renal function parameters do not figure in this protocol. We recommend continuous renal replacement therapy at 35 mL/kg/h (2,000 mL/1.73 m(2)/h), a dose that allows adequate flexibility in fluid management and that may provide effective clearance of proinflammatory (and anti-inflammatory) mediators that drive the evolving dysfunction. Proactive intervention improves the clinical status such that the transition to mechanical ventilation may proceed smoothly or in some cases even may be avoided altogether.

    View details for DOI 10.1016/j.semnephrol.2008.05.008

    View details for Web of Science ID 000259689000008

    View details for PubMedID 18790368

  • Patient selection critical for calcineurin inhibitor withdrawal in pediatric kidney transplantation PEDIATRIC TRANSPLANTATION Weintraub, L., Li, L., Kambham, N., Alexander, S., Concepcion, W., Miller, K., Wong, C., Salvatierra, O., Sarwal, M. 2008; 12 (5): 541-549


    CNI withdrawal may be employed as a "rescue" strategy for patients with established renal allograft injury and/or declining allograft function, with the aim at eliminating CNI-associated nephrotoxic effects. This analysis reviews outcomes in a pediatric population and identifies risk factors for adverse events post-CNI withdrawal. We performed a retrospective analysis of 17 pediatric renal transplants who underwent CNI withdrawal, with conversion to sirolimus and MMF. Mean CrCl decreased from 64.3 +/- 22 to 59.38 +/- 28.6 mL/min/1.73 m(2) (p = 0.04) at six months and 57.46 +/- 31.1 mL/min/1.73 m(2) (p = 0.02) at 12 months post-withdrawal. Forty-one percent of patients experienced AR. Increased risk for AR was associated with prior AR history, lower sirolimus trough levels, and lower CNIT biopsy scores. Graft loss (24%) was associated with worse CrCl, proteinuria, and histologic chronicity. Proteinuria (spot protein/creatinine ratio) increased from 0.75 +/- 1.0 to 1.71 +/- 2.0 (p = 0.03), unrelated to de novo sirolimus use. Four patients returned to CNI-based immunosuppression due to AR (n = 3) and gastrointestinal side effects (n = 1). Careful selection of pediatric candidates for CNI withdrawal is recommended. Worsening graft function and graft loss may be minimized by selecting patients with high CNIT scores and low biopsy chronicity and excluding patients with prior AR history.

    View details for DOI 10.1111/j.1399-3046.2007.00847.x

    View details for PubMedID 18564305

  • Safety and pharmacokinetics of daclizumab in pediatric renal transplant recipients PEDIATRIC TRANSPLANTATION Pescovitz, M. D., Knechtle, S., Alexander, S. R., Colombani, P., Nevins, T., Nieforth, K., Bouw, M. R. 2008; 12 (4): 447-455


    This study examined the safety and pharmacokinetics/pharmacodynamics of daclizumab in combination with mycophenolate mofetil (or azathioprine), corticosteroids, and cyclosporine or tacrolimus, in 61 pediatric renal allograft recipients in three age groups: less than or equal to five yr (n = 18), 6-12 yr (n = 18), and 13-17 yr (n = 25). The dosing regimen was daclizumab 1.0 mg/kg before transplantation, followed by four biweekly doses. The pharmacokinetics of daclizumab were described using NONMEM software. Median (range) estimated trough daclizumab levels achieved on day 56 (before dose 5) were 3.88 microg/mL (2.48-8.78), 4.54 microg/mL (1.79-18.7), and 4.94 microg/mL (0.05-10.6) in the less than or equal to five yr (n = 15), 6-12 yr (n = 17), and 13-17 yr (n = 22) age groups, respectively. Steady-state median (range) daclizumab exposures were 2040 mg x h/mL (1585-3778), 2757 mg x h/mL (1873-3494) and 3297 mg x h/mL (1705-6453), respectively. Saturation of the IL-2R occurred rapidly and was maintained for greater than or equal to three months after transplantation. Daclizumab was generally well-tolerated with no acute allergic or anaphylactic reactions, deaths or malignancies during the study. The proportion of patients who developed acute rejection at six and 12 months was 8.5% and 16.7%, respectively. This study shows that adding daclizumab at 1 mg/kg to standard immunosuppressive therapy provides safe and effective IL-2R blockade.

    View details for DOI 10.1111/j.1399-3046.2007.00830.x

    View details for Web of Science ID 000255551700014

    View details for PubMedID 18466432

  • Extended enrollment and analysis of a prospective steroid-free immunosuppression trial supports study safety and efficacy Li, L., Salvatierra, O., Concepcion, W., Wong, C., Alexander, S., Grimm, P., Martin, J., Sarwal, M. BLACKWELL PUBLISHING. 2008: 253–54
  • Continuous renal replacement therapy (CRRT) after stem cell transplantation. A report from the prospective pediatric CRRT Registry Group PEDIATRIC NEPHROLOGY Flores, F. X., Brophy, P. D., Symons, J. M., Fortenberry, J. D., Chua, A. N., Alexander, S. R., Mahan, J. D., Bunchman, T. E., Blowey, D., Somers, M. J., Baum, M., Hackbarth, R., Chand, D., McBryde, K., Benfield, M., Goldstein, S. L. 2008; 23 (4): 625-630


    Pediatric stem cell transplant (SCT) recipients commonly develop acute renal failure (ARF). We report the demographic and survival data of pediatric SCT patients enrolled in the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry. Since 1 January 2001, 51/370 (13.8%) patients entered in the ppCRRT Registry had received a SCT. Median age was 13.63 (0.53-23.52) years. The primary reasons for the initiation of continuous renal replacement therapy (CRRT) were treatment of fluid overload (FO) and electrolyte imbalance (49%), FO only (39%), electrolyte imbalance only (8%) and other reasons (4%). The CRRT modalities included continuous veno-veno hemodialysis (CVVHD), 43%, continuous veno-veno hemofiltration (CVVH), 37% and continuous veno-veno hemodiafiltration (CVVHDF), 20%. Seventy-six percent had multi-organ dysfunction syndrome (MODS), 72% received ventilatory support and the mean FO was 12.41 +/- 3.70%. Forty-five percent of patients survived. Patients receiving convective therapies had better survival rates (59% vs 27%, P < 0.05). Patients requiring ventilatory support had worse survival (35% vs 71%, P < 0.05). Mean airway pressure (Paw) at the end of CRRT was lower in survivors (8.7 +/- 2.94 vs 25.76 +/- 2.03 mmH(2)O, P < 0.05). Development of high mean airway pressure in non-survivors is likely related to non-fluid injury, as it was not prevented by early and aggressive fluid management by CRRT therapy.

    View details for DOI 10.1007/s00467-007-0672-2

    View details for Web of Science ID 000253683300016

    View details for PubMedID 18228045

  • Worldwide variation of dialysis-associated peritonitis in children KIDNEY INTERNATIONAL Schaefer, F., Feneberg, R., Aksu, N., Donmez, O., Sadikoglu, B., Alexander, S. R., Mir, S., Ha, I. S., Fischbach, M., Simkova, E., Watson, A. R., Moeller, K., von Baum, H., Warady, B. A. 2007; 72 (11): 1374-1379


    Peritonitis is the most common cause of dialysis failure in children on chronic peritoneal dialysis. We performed a prospective study of 501 peritonitis episodes in 44 pediatric dialysis centers located in 14 countries that examined peritonitis etiology, efficiency of opinion-based management guidelines, and final outcomes. Culture-negative incidence varied significantly from 11% in North America to 67% in Mexico. Argentina and North America had the highest rate of Gram-negative episodes. Pseudomonas-based peritonitis was eightfold more common in the United States than in Europe, and correlated with the frequency of exit site cleansing and topical mupirocin administration. Significant regional variation in antibiotic susceptibility was noted for the first generation cephalosporins and aminoglycosides. Initial response rates to standardized empiric antibiotic treatment did not differ between regions; however, final outcomes were significantly less favorable in Eastern Europe. The wide regional variation in culture-negative peritonitis, and the distribution and antibiotic susceptibilities of causative bacteria needs to be taken into consideration when the guidelines for empiric therapy of pediatric dialysis-associated peritonitis are revised.

    View details for DOI 10.1038/

    View details for Web of Science ID 000250955900017

    View details for PubMedID 17882152

  • The effect of vascular access location and size on circuit survival in pediatric continuous renal replacement therapy: A report from the PPCRRT registry INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS Hackbarth, R., Bunchman, T. E., Chua, A. N., Somers, M. J., Baum, M. A., Symons, J. M., Brophy, P. D., Blowey, D., Fortenberry, J. D., Chand, D., Flores, F. X., Alexander, S. R., Mahan, J. D., McBryde, K. D., Benfield, M. R., Goldstein, S. L. 2007; 30 (12): 1116-1121


    Well-functioning vascular access is essential for the provision of adequate CRRT. However, few data exist to describe the effect of catheter size or location on CRRT performance in the pediatric population.Data for vascular access site, size, and location, as well as type of anticoagulant used and patient demographic data were gathered from the ppCRRT registry. Kaplan-Meier curves were generated and then analyzed by log-rank test or Cox Proportional Hazards model.Access diameter was found to significantly affect circuit survival. None of the 5 French catheters lasted longer than 20 hours. Seven and 9 French, but not 8 French, catheters fared worse than larger diameter catheters (p=0.002). Circuits associated with internal jugular access survived longer than subclavian or femoral access associated circuits (p<0.05). Circuit survival was also found to be favorably associated with the CVVHD modality (p<0.001).Functional CRRT circuit survival in children is favored by larger catheter diameter, internal jugular vein insertion site and CVVHD. For patients requiring catheter diameters less than 10 French, CRRT circuit survival might be optimized if internal jugular vein insertion is feasible. Conversely, when a vascular access site other than the internal jugular vein is most prudent, consideration should be given to using the largest diameter catheter appropriate for the size of the child. The CVVHD modality was associated with longer circuit survival, but the mechanism by which this occurs is unclear.

    View details for Web of Science ID 000252851800012

    View details for PubMedID 18203074

  • Demographic characteristics of pediatric continuous renal replacement therapy: A report of the prospective pediatric continuous renal replacement therapy registry 11th Annual International Conference on Continuous Renal Replacement Therapies Symons, J. M., Chua, A. N., Somers, M. J., Baum, M. A., Bunchman, T. E., Benfield, M. R., Brophy, P. D., Blowey, D., Fortenberry, J. D., Chand, D., Flores, F. X., Hackbarth, R., Alexander, S. R., Mahan, J., McBryde, K. D., Goldstein, S. L. AMER SOC NEPHROLOGY. 2007: 732–38


    This article reports demographic characteristics and intensive care unit survival for 344 patients from the Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry, a voluntary multicenter observational network.Ages were newborn to 25 yr, 58% were male, and weights were 1.3 to 160 kg. Patients spent a median of 2 d in the intensive care unit before CRRT (range 0 to 135). At CRRT initiation, 48% received diuretics and 66% received vasoactive drugs. Mean blood flow was 97.9 ml/min (range 10 to 350 ml/min; median 100 ml/min); mean blood flow per body weight was 5 ml/min per kg (range 0.6 to 53.6 ml/min per kg; median 4.1 ml/min per kg). Days on CRRT were <1 to 83 (mean 9.1; median 6). A total of 56% of circuits had citrate anticoagulation, 37% had heparin, and 7% had no anticoagulation.Overall survival was 58%; survival differed across participating centers. Survival was lowest (51%) when CRRT was started for combined fluid overload and electrolyte imbalance. There was better survival in patients with principal diagnoses of drug intoxication (100%), renal disease (84%), tumor lysis syndrome (83%), and inborn errors of metabolism (73%); survival was lowest in liver disease/transplant (31%), pulmonary disease/transplant (45%), and bone marrow transplant (45%). Overall survival was better for children who weighed >10 kg (63 versus 43%; P = 0.001) and for those who were older than 1 yr (62 versus 44%; P = 0.007).CRRT can be used successfully for a wide range of critically ill children. Survival is best for those who have acute, specific abnormalities and lack multiple organ involvement; sicker patients with selected diagnoses may have lower survival. Center differences might suggest opportunities to define best practices with future study.

    View details for DOI 10.2215/CJN.03200906

    View details for Web of Science ID 000247612700018

    View details for PubMedID 17699489

  • Peritonitis in children who receive long-term peritoneal dialysis: A prospective evaluation of therapeutic guidelines JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Warady, B. A., Feneberg, R., Verrina, E., Flynn, J. T., Mueller-Wiefel, D. E., Besbas, N., Zurowska, A., Aksu, N., Fischbach, M., Sojo, E., Donmez, O., Sever, L., Sirin, A., Alexander, S. R., Schaefer, F. 2007; 18 (7): 2172-2179


    In children who are on chronic peritoneal dialysis, peritonitis is the primary complication compromising technique survival, and the optimal therapy of peritonitis remains uncertain. An Internet-based International Pediatric Peritonitis Registry was established in 47 pediatric centers from 14 countries to evaluate the efficacy and safety of largely opinion-based peritonitis treatment guidelines in which empiric antibiotic therapy was stratified by disease severity. Among a total of 491 episodes of nonfungal peritonitis entered into the registry, Gram-positive organisms were cultured in 44%, Gram-negative organisms were cultured in 25%, and cultures remained negative in 31% of the episodes. In vitro evaluation revealed 69% sensitivity of Gram-positive organisms to a first-generation cephalosporin and 80% sensitivity of Gram-negative organisms to a third-generation cephalosporin. Neither the risk factors assumed by the guidelines nor the choice of empiric therapy was predictive of either the early treatment response or the final functional outcome of the peritonitis episodes. Overall, 89% of cases achieved full functional recovery, a portion after relapsing peritonitis (9%). These data serve as the basis for new evidence-based guidelines. Modification of empiric therapy to include aminoglycosides should be considered.

    View details for DOI 10.1681/ASN.2006101158

    View details for Web of Science ID 000248758500025

    View details for PubMedID 17582162

  • The impact of steroid avoidance on early and intermediate renal allograft function. Weintraub, L. A., Li, L., Alexander, S. R., Oscar, S., Minnie, S. M. WILEY-BLACKWELL. 2007: 37–37
  • Subclinical cytomegalovirus and Epstein-Barr virus viremia are associated with adverse outcomes in pediatric renal transplantation PEDIATRIC TRANSPLANTATION Li, L., Chaudhuri, A., Weintraub, L. A., Hsieh, F., Shah, S., Alexander, S., Salvatierra, O., Sarwal, M. M. 2007; 11 (2): 187-195


    Post-transplant clinical disease with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) is a known risk factor for graft dysfunction and lymphoproliferation. We postulate that subclinical, asymptomatic viremia also adversely impacts outcomes, and may warrant re-assessment of current monitoring and antiviral prophylaxis protocols. A single-center study was conducted on 102 pediatric (51 steroid-free and 51 matched steroid-based historical controls). Quantitative viral loads were serially monitored and correlated with outcome measures. Overall, the incidence of CMV and EBV clinical disease was 5% (1% CMV and 4% EBV); however, the incidence of subclinical viremia was 44% (12.7% CMV, 38.2% EBV, 6.9% CMV + EBV). Risk factors for subclinical viremia were EBV naivety (p = 0.07), age less than five yr (p = 0.04), lack of prophylaxis (p = 0.01), and steroid usage (p = 0.0007). Subclinical viremia was associated with lower three-yr graft function (p = 0.03), increased risk of acute rejection (odds ratio 2.07; p = 0.025), hypertension (p = 0.04), and graft loss (p = 0.03). Subclinical asymptomatic CMV and EBV viremia is a risk factor for graft injury and loss. These findings support the need for aggressive, serial viral monitoring to better determine the appropriate length of post-transplant antiviral prophylaxis, and to determine the effect of immunosuppression protocols on the development of viremia.

    View details for DOI 10.1111/j.1399-3046.2006.00641.x

    View details for PubMedID 17300499

  • Proteinuria in pediatric renal transplant recipients during the first 60 post-transplant days PEDIATRIC TRANSPLANTATION Chua, A. N., Alexander, S. R., Sarwal, M. M., Millan, M., Salvatierra, O., Yorgin, P. D. 2006; 10 (8): 957-961


    Although normative values of post-transplant proteinuria have been reported in adults, data for pediatric renal transplant recipients have not been previously published. We hypothesized that pediatric renal transplant recipients achieve normal urinary protein to creatinine (UProt/UCr) ratios (<0.2) by 60 days post-transplant in the absence of early recurrent disease. Retrospective chart review of 108 consecutive pediatric renal transplant recipients at Stanford University was performed. Thirty-two (30%) patients who were eligible had > or = 1 UProt/UCr ratio obtained during the first 60 post-transplant days. Mean age at transplant was 13.9 +/- 4.2 yr. UProt/UCr ratios were grouped by week post-transplant for quantile analysis. Mean weekly UProt/UCr values were not lower than 0.2 until the ninth post-transplant week. No difference in post-transplant proteinuria existed between nephrectomized and non-nephrectomized transplant recipients. Experience with a single patient with proven focal segmental glomerulosclerosis (FSGS) recurrence suggests that normative UProt/UCr data may be useful in early identification of patients experiencing disease recurrence. Univariate correlations demonstrated that UProt/UCr negatively correlated with serum albumin levels (-0.415, p < 0.0001) and days post-transplant (-0.531, p < 0.0001). Independent of primary diagnosis, proteinuria persists throughout the first 60 days in most pediatric renal transplant patients, decreasing relative to time post-transplant.

    View details for DOI 10.1111/j.1399-3046.2006.00594.x

    View details for Web of Science ID 000241678100016

    View details for PubMedID 17096766

  • The hemophagocytic syndrome: Titrating continuous hemofiltration to the degree of lactic acidosis PEDIATRIC HEMATOLOGY AND ONCOLOGY DiCarlo, J., Lui, W. Y., Frankel, L., Howell, W., Schiffman, J., Alexander, S. 2006; 23 (7): 599-610


    In 3 cases of severe multiple organ failure due to hemophagocytic lymphohistiocytosis (HLH) in children, the authors demonstrate the utility of continuous hemofiltration in attenuating the consequences of excess cytokine activity, with therapy titrated to the degree of lactic acidosis. HLH was diagnosed in 3 encephalopathic children with multiple organ failure, elevated ferritin (49,396-237,582 pmol/L; or 21,983-105,733 ng/mL), elevated serum triglyceride, and depressed cell lines. One had a known malignancy, one had EBV-associated lymphoproliferative disease, and one was previously healthy. Continuous hemofiltration was initiated, with the ultrafiltrate production rate and countercurrent dialysate flow titrated to metabolic acidosis as reflected by the serum lactate (maximum 3.5 mmol/L or 31.6 mg/dL). Hemofiltration was titrated upward until lactic acidosis resolved, through clearance of lactate or interruption of excess cytokine-driven activity; maximum prescription was 2000 mL/h ultrafiltrate production plus 2500 mL/h dialysate flow. Stability was achieved with hemofiltration, then substantial resolution occurred with treatment according to the HLH-94 protocol (dexamethasone, cyclosporin, VP-16, intrathecal methotrexate). One child succumbed to candidiasis. Another made a full recovery. A third succumbed to his primary malignancy. HLH should be suspected in unexplained or unresolving multiple organ failure. Titration of hemofiltration based on measurable parameters of cellular metabolism (e.g., lactate, base deficit) may stabilize the child with metabolic acidosis long enough to allow proper diagnosis and institution of definitive therapy. Hemofiltration is not a panacea but rather a stabilizing mechanism, with poorly understood effects on interstitial water and solute flux, that facilitates recovery over weeks, not days.

    View details for DOI 10.1080/08880010600860768

    View details for PubMedID 16928655

  • A technique for rapid exchange of continuous renal replacement therapy PEDIATRIC NEPHROLOGY Yorgin, P., Ludlow, M., Chua, A., Alexander, S. 2006; 21 (5): 743-746


    Re-initiation of continuous renal replacement therapy (CRRT) in neonates and young infants weighing less than 15 kg often necessitates a blood prime of the blood circuit path or a concurrent packed red blood cell (PRBC) transfusion to avoid causing hemodynamic instability due to acute hemodilution. The significant amount of time required for a routine CRRT circuit change can be associated with worsening electrolyte and acid-base abnormalities, fluid retention, greater hemodynamic instability and reducing effective hemofiltration time. In an attempt to limit the time without CRRT and to eliminate the requirement for additional blood exposure, a new technique, rapid exchange of continuous renal replacement therapy (RECRRT), was developed. Rapid exchange of continuous renal replacement therapy is a sequential technique that transfers citrated blood from one CRRT machine to another machine connected in series. The technique effectively negates the requirement for CRRT circuit path blood priming or PRBC transfusion. The amount of time without CRRT is markedly reduced by RECRRT to 2-3 min. The RECRRT technique has been utilized more than 30 times for at least 15 patients without an adverse event. RECRRT may benefit children who weigh less than 15 kg and in those patients who experience hemodynamic or clinical instability while CRRT is discontinued for only a brief period.

    View details for DOI 10.1007/s00467-006-0050-5

    View details for Web of Science ID 000237189700024

    View details for PubMedID 16534605

  • Option of pre-emptive nephrectomy and renal transplantation for Bartter's syndrome PEDIATRIC TRANSPLANTATION Chaudhuri, A., Salvatierra, O., Alexander, S. R., Sarwal, M. M. 2006; 10 (2): 266-270


    Bartter's syndrome (BS) is an incurable genetic disease, with variable response to supportive therapy relating to fluid and electrolyte management. Poor control or therapy non-compliance may result in frequent life threatening episodes of dehydration, acidosis and hypokalemia, with resultant adverse effects on patient quality of life (QOL). We report, for the first time, pre-emptive bilateral native nephrectomies and successful renal transplantation, prior to the onset of ESRD, for severe, clinically brittle, neonatal BS, resulting in correction of metabolic abnormalities and excellent graft function. We propose that fragile BS should be considered as a possible indication for early native nephrectomies and pre-emptive renal transplantation, procedures that results in a 'cure' for the underlying disease and significant improvements in patient QOL.

    View details for DOI 10.1111/j.1399-3046.2005.00435.x

    View details for PubMedID 16573620

  • Clinical review: Alternative vascular access techniques for continuous hemofiltration CRITICAL CARE DiCarlo, J. V., Auerbach, S. R., Alexander, S. R. 2006; 10 (5)


    Obtaining or maintaining vascular access for continuous hemofiltration can sometimes be problematic, especially in the child or adult in multiple organ failure with edema and/or coagulopathy. Problems commonly encountered include obstruction of the femoral vein by the catheter, insertion difficulties, safety concerns when cannulating the subclavian vein in coagulopathy, and catheter and circuit occlusion due to disseminated intravascular coagulation. For access in infants we describe a technique utilizing two single-lumen thin-walled vascular sheaths. For infants and small children initial access to the vein may be difficult due to edema or poor perfusion. For this situation we describe the 'mini-introducer' technique of securing the vein and facilitating subsequent insertion of a relatively large guide wire. At any age an alternative route to the subclavian vein, from above the clavicle, is potentially 'compressible' in the event of hemorrhage during the procedure. We remind the reader of the utility of ultrasound guidance for cannulation of the internal jugular and subclavian veins. And lastly we review the options for venous return via the umbilical vein in infants, and via the antecubital vein in larger children and adults.

    View details for DOI 10.1186/cc5035

    View details for Web of Science ID 000247718300037

    View details for PubMedID 16989669

    View details for PubMedCentralID PMC1751070

  • Hemofiltration for cytokine-driven illnesses: The mediator delivery hypothesis 10th International Conference on Continuous Renal Replacement Therapies Di Carlo, J. V., Alexander, S. R. WICHTIG EDITORE. 2005: 777–86


    Hemofiltration is evolving as an adjunctive therapy for sepsis and other forms of systemic inflammation. Designed as a substitute for lost renal function, it is sometimes employed prior to the onset of renal failure to facilitate the nonspecific clearance of pro-inflammatory mediators. Prevailing theories suggest that hemofiltration attenuates the immune response when a threshold amount of excess cytokine is removed at the semi-permeable membrane. In this article we introduce an alternative hypothesis, in which hemofiltration exerts its effect by reinvigorating lymphatic flow and function. Crystalloid "replacement" solution, as much as 48 to 72 liters daily, is infused to restore intravascular volume lost through production of ultrafiltrate. Partial redistribution into interstitium and lymph mobilizes inflammatory mediators and other proteins, cellular byproducts, excessive ground matrix, fragments of apoptotic cells and free DNA. These substances are then metabolized, scavenged or cleared at multiple sites, including the reticuloendothelial system, liver, kidney, erythrocyte, and hemofilter.

    View details for Web of Science ID 000232480700003

    View details for PubMedID 16211527

  • Proteinuria in pediatric renal transplant recipients during the first posttransplant month. 6th American Transplant Congress Chua, A. N., Alexander, S. R., Sarwal, M. M., MILLAN, M., Salvatierra, O., Yorgin, P. D. WILEY-BLACKWELL. 2005: 496–496
  • A rational approach to setting tacrolimus target levels in pediatric and young adult renal transplant recipients. 6th American Transplant Congress Chua, A. N., Lemley, K. V., Alexander, S. R., Yorgin, P. D. WILEY-BLACKWELL. 2005: 497–497
  • The international pediatric peritonitis registry: A global internet-based initiative in pediatric dialysis 1st Joint Congress of the International-Society-for-Peritoneal-Dialysis/European Peritoneal Dialysis Meeting Feneberg, R., Warady, B. A., Alexander, S. R., Schaefer, F. MULTIMED INC. 2005: S130–S134


    Recommendations for the management of peritoneal dialysis-associated peritonitis in children have recently been developed by an International Society for Peritoneal Dialysis (ISPD) expert committee. The International Pediatric Peritonitis Registry (IPPR) was established in October 2001 as a global consortium of 47 pediatric dialysis centers in order to assess the validity of these guidelines.The IPPR is an internet-based registry collecting data on pediatric peritonitis episodes treated according to the ISPD guidelines. Data on 375 episodes have been collected as of July 2004. DATA ACQUISITION: Detailed data are obtained online on the diagnosis of peritonitis, antibiotic and adjunctive therapy, as well as on possible risk factors and treatment results.Final data analysis of the IPPR will yield extensive information on the treatment and outcome of peritoneal dialysis-associated peritonitis in children.

    View details for Web of Science ID 000230035800034

    View details for PubMedID 16048278

  • Clinical parameters associated with renal pathology after one year of cyclophosphamide (CTX) in pediatric SLE. 68th Annual Scientific Meeting of the American-College-of-Rheumatology/39th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals Hsu, J., Chira, P., Troxell, M., Balboni, I., Holmes, T., Chua, A., Alexander, S., Sandborg, C. WILEY-BLACKWELL. 2004: 4094–94
  • Hyperhomocysteinemia in pediatric and young adult renal transplant recipients PEDIATRIC TRANSPLANTATION Belson, A., Sanchez, J., Alexander, S. R., Salvatierra, O., Dar, M. H., Reif, S., Yorgin, P. D. 2004; 8 (2): 161-166


    Hyperhomocysteinemia (HHcy) has been recently identified as an important and reversible cardiovascular risk factor in adult and pediatric renal transplant recipients. A retrospective cross-sectional analysis of 70 pediatric and young adult renal transplant recipients was performed to determine the prevalence, and important clinical and laboratory correlates of HHcy. Total homocysteine concentration, free and protein bound, was determined by fluorescence polarization immunoassay using an IMX analyzer. Hyperhomocysteinemia was defined as a serum homocysteine (Hcy) level above the 95th percentile for age. Fifty-four of 70 patients (77%) had HHcy. Comparison of patients with HHcy with patients without HHcy demonstrated no statistical difference in age (p = 0.35), gender (p = 0.76) or donor type (p = 0.20). Patients with HHcy had significantly lower calculated creatinine clearance values (Ccr) (p = 0.02), 67.3 +/- 21.2 mL/min/1.73 m(2) vs. 90.7 +/- 32.3 mL/min/1.73 m(2) for patients without HHcy. Immunosuppression did not correlate with the diagnosis of HHcy. Stepwise logistic regression identified patient age (0.18, p = 0.013) and Ccr (-0.04, p = 0.011) as significant variables. In conclusion, HHcy is more common than expected in pediatric renal transplant recipients. Patients with Ccr <80 mL/min/1.73 m(2) were statistically more likely to have a diagnosis of HHcy. We recommend that Hcy levels should be evaluated in this high risk population.

    View details for Web of Science ID 000220486000011

    View details for PubMedID 15049796

  • Safety and pharmacokinetics of ascending single doses of sirolimus (Rapamune (R), rapamycin) in pediatric patients with stable chronic renal failure undergoing dialysis PEDIATRIC TRANSPLANTATION Tejani, A., Alexander, S., Ettenger, R., Lerner, G., Zimmerman, J., Kohaut, E., Briscoe, D. M. 2004; 8 (2): 151-160


    Sirolimus (Rapamune, rapamycin) has been shown to be an effective and safe immunosuppressive drug in adult kidney transplant patients when administered concomitantly with cyclosporine (CsA) and steroids. This study reports on a phase 1 assessment of the drug's tolerance, safety, and pharmacokinetic parameters in pediatric patients. The safety and pharmacokinetic profiles of ascending single doses of sirolimus oral solution were investigated in 32 clinically stable pediatric patients on chronic hemodialysis (n = 26) or peritoneal dialysis (n = 6). Patients were divided into two age groups (5-11 and 12-18 yr), and each patient received either a single dose of sirolimus (1, 3, 9, or 15 mg/m(2)) or placebo. Whole blood and plasma samples were collected from each patient for the determination of sirolimus pharmacokinetic parameters. Safety assessments were based on reports of adverse events and results of scheduled physical examinations, vital sign measurements and clinical laboratory tests. The younger patients (5-11 yr) showed statistically significant increases in whole blood sirolimus t(max) (p < or = 0.05) and weight-normalized CL/F (p<0.05) when compared with older patients (12-18 yr). There were no differences in terminal t(1/2), V(ss)/F, dose-normalized peak concentration (C(max)) and AUC, or the B/P. The whole blood sirolimus mean t(max) and weight-normalized CL/F in younger patients were increased by approximately 41.5% and 30%, respectively. Whole blood sirolimus concentrations exhibited less than proportional increases with ascending doses, which may have been caused by the large inter-subject variability in CL/F, small number of subjects, and a potentially inherent decrease in sirolimus bioavailability in younger pediatric patients. Adverse events occurred in all dose and age groups, with headache and stomach pain being the most frequently observed events. No deaths or serious adverse events were reported, and no patient withdrew from the study because of an adverse event. Based on an inter-study analysis, weight-normalized CL/F in the current population of younger pediatric dialysis patients (5-11 yr, 544 +/- 463 mL/h/kg, n = 7) was increased by 90% (p < or = 0.05) compared with healthy adults (19-36 yr, 287 +/- 111 mL/h/kg, n = 25). These results suggest that younger pediatric patients might require an increased maintenance dose of sirolimus to achieve whole blood exposures similar to those in healthy adults. Sirolimus is well tolerated as a single dose of 1, 3, 9, or 15 mg/m(2).

    View details for Web of Science ID 000220486000010

    View details for PubMedID 15049795

  • The use of art therapy to detect depression and post-traumatic stress disorder in pediatric and young adult renal transplant recipients PEDIATRIC TRANSPLANTATION Wallace, J., Yorgin, P. D., Carolan, J., Moore, H., Sanchez, J., Belson, A., Yorgin, L., MAJOR, C., Granucci, L., Alexander, S., Arrington, D. 2004; 8 (1): 52-59


    Pediatric and young adult renal transplant recipients may experience feelings of depression and emotional trauma. A study was conducted to (1) determine the prevalence of depression and emotional trauma and (2) assess the utility of the Formal Elements of Art Therapy Scale (FEATS). Sixty-four renal transplant recipients, 6-21 yr of age, were evaluated using self-report measures (CDI and Davidson) and art-based assessments. Subject art was analyzed by art therapists using seven of the 14 elements of the (FEATS), to assess depression. Unlike CDI and Davidson self-report testing, all patients were able to complete the art-based directives. When self-report measures and art-based assessments were combined, 36% of the study population had testing results consistent with depression and/or post-traumatic stress. The FEATS assessments identified a subset of patients who were not identified using the self-report measures. There was a correlation between CDI and Davidson scores (p < 0.0001), Davidson scores correlated with hospital days (p = 0.05), and FEATS correlated with height Z score (p = 0.04) and donor type (p = 0.01). Patients who required psychological interventions including antidepressant therapy, psychological counseling and psychiatric hospitalization during the year after the study were identified as depressed. Sensitivity for FEATS and CDI were 22 and 50% respectively. The results suggest that while art therapy may be of utility in the identification of pediatric and young adult transplant recipients who are suffering from depression, FEATS analysis appears to lack sufficient sensitivity to warrant its use in this population. Study of other quantitative art-based assessment techniques may be warranted.

    View details for Web of Science ID 000189007000009

    View details for PubMedID 15009841

  • The Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) registry: Design, development and data assessed INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS Goldstein, S. L., Somers, M. J., BROPHY, P., Bunchman, T., Baum, M., Blowey, D., Mahan, J. D., Flores, F. X., Fortenberry, J. D., Chua, A., Alexander, S. R., Hackbarth, R., Symons, J. M. 2004; 27 (1): 9-14


    Many issues plague the pediatric ARF outcome literature, which include data only from single center sources, a relative lack of prospective study, mixture within studies of renal replacement therapy modality without stratification and inconsistent use of methods to control for patient illness severity in outcome analysis. Since January 2001, the Prospective Pediatric CRRT (ppCRRT) Registry Group has been collecting data from multiple United States pediatric centers to obtain demographic data regarding pediatric patients who receive CRRT, assess the effect of different CRRT prescriptions on circuit function and evaluate the impact of clinical variables on patient outcome. The aim of the current paper is to describe the ppCRRT Registry design, review the decision process and rationale for the options chosen for the ppCRRT format and discuss the analysis plan and future projects envisioned for the ppCRRT Registry.

    View details for Web of Science ID 000189017600004

    View details for PubMedID 14984178

  • Postdialysis albumin: A better nutrition marker in pediatric hemodialysis patients? JOURNAL OF RENAL NUTRITION Wapensky, T., Alexander, S. R., Sarwal, M. 2004; 14 (1): 45-51


    Prehemodialysis serum albumin is considered an important indicator of nutritional status in pediatric hemodialysis (HD) patients. Study aim To determine whether serum albumin levels changed significantly from predialysis to postdialysis, and correlated with fluid changes over HD treatment.We prospectively measured pre-HD and post-HD albumin levels in 9 pediatric patients (ages 10 to 20 years; mean age, 16.3 years) on HD over an 8-month period. Changes in weight and albumin over 45 HD treatments were compared.A total of 66.7% of pre-HD and 100% of post-HD albumin levels were within the normal range. Post-HD albumin was significantly higher than pre-HD in 42 of 45 observations (Mean, 4.7 +/- 0.39 g/dL versus 3.8 +/- 0.37; P <.0001). Delta albumin/treatment inversely correlated with weight loss (r = 0.741, P <.0001) and prescribed ultrafiltration rate (r = 0.764, P <.0001)Serum albumin levels increase significantly postdialysis and inversely correlate with fluid removal. Pre-HD albumin level may not be a valid indicator of protein status because of the confounding effect of interdialytic weight gain, and may instead be a marker for fluid overload. Further studies are needed to assess the value of postdialysis albumin level as an indicator of nutritional status in pediatric HD patients.

    View details for DOI 10.1053/

    View details for Web of Science ID 000188453300008

    View details for PubMedID 14740330

  • Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation TRANSPLANTATION Sarwal, M. M., Vidhun, J. R., Alexander, S. R., Satterwhite, T., MILLAN, M., Salvatierra, O. 2003; 76 (9): 1331-1339


    Corticosteroids have been invariant transplant immunosuppressives with numerous adverse effects. We previously reported 6-month results in 10 patients using extended daclizumab induction to safely eliminate steroid use in pediatric renal transplantation. This expanded pilot series discusses immunosuppression dosing modification to further minimize drug toxicity without sacrificing regimen efficacy.Fifty-seven pediatric renal transplant recipients were enrolled in the pilot steroid-free protocol. Extended daclizumab induction, tacrolimus, and mycophenolate mofetil (MMF) were intended maintenance drugs. Fourteen patients were equal to or younger than 5 years, and 43 patients were older than 5 years of age at transplantation. There were seven protocol breaks. Study patients underwent serial protocol transplant biopsies (n=246), and serum daclizumab and mycophenolic acid (MPA) trough levels were evaluated. In this efficacy study, controls were 50 historical-matched steroid-based children receiving tacrolimus with 100% 2-year graft survival and without delayed graft function.Mean follow-up was 20 (range, 4.5-41) months with 98% overall graft and patient survival. At 1 year of analysis, steroid-free recipients showed significant improvements for clinical acute rejection (8%), graft function, hypertension, and growth, without increased infectious complications. Leukopenia, anemia, and allograft nephrotoxicity were addressed by solely decreasing MMF and tacrolimus dosing and/or by replacing MMF with sirolimus, without increasing acute rejection. Early daclizumab levels of more than 5 microg/mL were observed for the first time in children of all ages.Pediatric renal transplantation is safe without steroids. Daclizumab first-dose doubling and extended use for 6 months replaces steroids effectively without evidence of overimmunosuppression and may be the pivotal cause for the reduced acute rejection seen in this trial. This pilot study provides preliminary data to test this protocol in a prospective, multicenter randomized study.

    View details for DOI 10.1097/01.TP.0000092950.54184.67

    View details for Web of Science ID 000186653100011

    View details for PubMedID 14627912

  • Spectrum and management of PD-associated peritonitis in children: Initial results of a global registry. Schaefer, F., Feneberg, R., Alexander, Warady, B. A. LIPPINCOTT WILLIAMS & WILKINS. 2003: 219A–220A
  • Continuous veno-venous hemofiltration may improve survival from acute respiratory distress syndrome after bone marrow transplantation or chemotherapy JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY DiCarlo, J. V., Alexander, S. R., Agarwal, R., Schiffman, J. D. 2003; 25 (10): 801-805


    Acute respiratory distress syndrome (ARDS) may result from immunologic activity triggered by irradiation and/or chemotherapy. Hemofiltration removes plasma water and soluble components below 25 kilodaltons. The authors hypothesized that early hemofiltration might attenuate the inflammatory component of ARDS, resulting in increased survival in immunocompromised children and young adults.Ten children (6 bone marrow transplantation, 3 chemotherapy, 1 lymphoma/hemophagocytosis) with ARDS (Pao2/Fio2 94 +/- 37 torr) received early continuous veno-venous hemodiafiltration as adjunctive therapy for respiratory failure, regardless of renal function. Six children had normal urine output and initial serum creatinine (range 0.1-1.2 mg/dL); four had renal insufficiency (initial creatinine 1.7-2.4 mg/dL). Hemofiltration was instituted coincident with intubation. Respiratory failure was precipitated by Enterobacter sepsis in two patients and by Aspergillus in one.Hemodiafiltration was performed for 13 +/- 9 days. A high rate of clearance was achieved (52 +/- 17 mL/min/1.73 m2). Duration of mechanical ventilation was 14 +/- 9 days. Nine of the 10 children were successfully extubated; 8 survived.Early hemofiltration may improve survival from ARDS following bone marrow transplantation or chemotherapy. Possible mechanisms include strict fluid balance, immunomodulation through filtration of inflammatory constituents, and immunomodulation through intensive extracellular water exchange that delivers biochemicals to organs of metabolism as well as the hemofilter.

    View details for PubMedID 14528104

  • "Flush before fill" in children receiving automated peritoneal dialysis PERITONEAL DIALYSIS INTERNATIONAL Warady, B. A., Ellis, E. N., Fivush, B. A., Lum, G. M., Alexander, S. R., Brewer, E. D., Ogrinc, F., Watkins, S. L. 2003; 23 (5): 493-498


    To evaluate the impact of the "flush before fill" technique on the frequency of peritonitis in children receiving automated peritoneal dialysis (APD).Randomized prospective multicenter study.Participating pediatric dialysis programs of the Pediatric Peritoneal Dialysis Study Consortium.121 pediatric (< 21 years of age) patients that had received peritoneal dialysis for > or = 2 months and that were currently receiving APD were randomized to use (flush group) or non-use (no flush group) of the "flush before fill" option. 66 patients were followed for > or = 12 months.Peritonitis rates.Overall, patients enrolled in the flush group experienced a peritonitis rate of 1 infection every 16.8 patient months; patients in the no flush group experienced a rate of 1 infection every 12.6 patient months (p = 0.193). However, analysis by gender revealed the peritonitis rate of females in the flush group (1 infection every 44.7 patient months) to be significantly better than females in the no flush group (1 infection every 12.4 patient months) (p < or = 0.01). There was no difference noted in the male patients.The use of the "flush before fill" option in pediatric patients receiving APD is associated with a marked improvement in the peritonitis rate of female but not male patients. Further study is indicated to explain the gender differences.

    View details for Web of Science ID 000186121800016

    View details for PubMedID 14604204

  • Early CVVH increases survival from bone marrow transplant ARDS DiCarlo, J. V., Alexander, Agarwal-Hashmi, R., Schiffman, J. D. INT PEDIATRIC RESEARCH FOUNDATION, INC. 2003: 274A–275A
  • Outcome of renal transplantation in adolescents with focal segmental glomerulosclerosis Symposium on Transplantation in Adolescents Baum, M. A., Ho, M., Stablein, D., Alexander, S. R. WILEY-BLACKWELL PUBLISHING, INC. 2002: 488–92


    Using the NAPRTCS database from January 1987 to January 2001, we examined 2687 adolescent (age 13-17 yr) index renal transplants to analyze differences in demographic treatment, and outcomes in adolescents with FSGS compared to other renal disease. 338 (12.6%) of adolescents had a primary diagnosis of FSGS. Adolescents with FSGS were more likely to be black and less likely to receive pre-emptive transplants (p < 0.001). No differences existed in HLA matching or immunosuppression regimens. Acute tubular necrosis occurred in more FSGS adolescents compared to non-FSGS adolescents following LD (11% vs. 4.7%) or CD (25.1% vs. 17.8%) transplants (p < 0.001). There were no significant differences in acute rejection rates between adolescents with FSGS and other adolescents. Graft survival was worse for LD FSGS adolescents (6 yr, 56%) compared to non-FSGS adolescents (77%) (p < 0.001) and was not significantly different from CD graft survival in FSGS (51%) or non-FSGS groups (61%). The relative risk (RR) of graft failure was greatest in LD transplant with FSGS (RR = 1.75; p < 0.001), compared to LD transplants without FSGS (RR = 1.0). Recurrent primary disease accounted for 15.2% of all graft failures in adolescents transplanted for FSGS with no difference between LD (17%) or CD (13.8%) grafts. Recurrent disease accounted for 3.2% of graft failures in adolescents without FSGS. Recurrent disease was the only cause of graft failure that differed between groups (p < 0.001). When compared to patients up to age 12 yr with FSGS, graft survival in both LD and CD transplants was worse in adolescents with FSGS (LD p = 0.035, CD p < 0.001). In conclusion, FSGS has a negative impact on graft survival in adolescents. Recurrence of FSGS results in a loss of the expected LD graft survival advantage in adolescents. Furthermore, adolescents with FSGS have decreased graft survival compared to younger children with FSGS. These data suggest that the rationale for LD transplantation in adolescents with FSGS should be based on factors other than the increased graft survival typically seen with LD transplantation.

    View details for Web of Science ID 000179493600007

    View details for PubMedID 12453201

  • CVVH improves survival from ARDS after bone marrow transplantation DiCarlo, J., Alexander, S., Agarwal, R., Schiffman, J. LIPPINCOTT WILLIAMS & WILKINS. 2002: A87
  • Unexpectedly high prevalence of posttransplant anemia in pediatric and young adult renal transplant recipients AMERICAN JOURNAL OF KIDNEY DISEASES Yorgin, P. D., Belson, A., Sanchez, J., Al Uzri, A. Y., Sarwal, M., Bloch, D. A., Oehlert, J., Salvatierra, O., Alexander, S. R. 2002; 40 (6): 1306-1318


    Although posttransplant anemia (PTA) is recognized as a common problem in adult renal transplant recipients, few pediatric studies have been published.In this retrospective cohort study of 162 pediatric renal transplant recipients treated at Stanford University, the authors sought to determine the prevalence, severity, and the predictive factors of PTA. Anemia was defined as a hematocrit (HCT) level greater than 2 SD below published means for age or as erythropoietin dependency to maintain a normal HCT.Sixty-seven percent of pediatric renal transplant recipients were anemic at the time of transplantation. The prevalence of anemia increased to 84.3% in the first month posttransplant. From 6 months to 60 months posttransplant, the prevalence of anemia remained high at 64.2% to 82.2%. Only 4 patients (2.5%) were never anemic. Iron depletion was detected in 19 of 26 and 23 of 23 anemic patients 12 and 60 months posttransplant, respectively. Serum erythropoietin levels were low relative to hematocrit levels in 38 of 56 anemic patients. Logistic regression at 3 months posttransplant showed that discharge hematocrit level (P < 0.0001), calcium (P = 0.0004), and cyclosporine dose (P = 0.0002) correlated with anemia. Creatinine clearance (P = 0.002) and white blood cell count (P = 0.004) correlated with anemia at 12 months posttransplant, but only creatinine clearance (P = 0.011) correlated with anemia 60 months posttransplant.Nearly all pediatric renal transplant recipients experience PTA. However, few children less than 2 years of age were anemic during the first year posttransplant. Antirejection therapy, bone disease, iron depletion, and creatinine clearance appear to play pivotal roles in the development of PTA in children.

    View details for DOI 10.1053/ajkd.2002.36910

    View details for Web of Science ID 000179581900025

    View details for PubMedID 12460052

  • Identification of Epstein-Barr virus-specific CD8(+) T lymphocytes in the circulation of pediatric transplant recipients TRANSPLANTATION Falco, D. A., Nepomuceno, R. R., Krams, S. M., Lee, P. P., DAVIS, M. M., Salvatierra, O., Alexander, S. R., Esquivel, C. O., Cox, K. L., Frankel, L. R., Martinez, O. M. 2002; 74 (4): 501-510


    Pediatric transplant recipients are at increased risk for Epstein Barr virus (EBV)-related B cell lymphomas. In healthy individuals, the expansion of EBV-infected B cells is controlled by CD8+ cytotoxic T cells. However, immunosuppressive therapy may compromise antiviral immunity. We identified and determined the frequency of EBV-specific T cells in the peripheral blood of pediatric transplant recipients.HLA-B*0801 and HLA-A*0201 tetramers folded with immunodominant EBV peptides were used to detect EBV-specific CD8+ T cells by flow cytometry in peripheral blood mononuclear cells from 24 pediatric liver and kidney transplant recipients. The expression of CD38 and CD45RO on EBV-specific, tetramer-binding cells was also examined in a subset of patients by immunofluorescent staining and flow cytometry.Tetramer-binding CD8+ T cells were identified in 21 of 24 transplant recipients. EBV-specific CD8+ T cells were detected as early as 4 weeks after transplant in EBV seronegative patients receiving an organ from an EBV seropositive donor. The frequencies (expressed as a percentage of the CD8+ T cells) of the tetramer-binding cells were HLA-B8-RAKFKQLL (BZLF1 lytic antigen peptide) tetramer, range=0.96 to 3.94%; HLA-B8-FLRGRAYGL (EBNA3A latent antigen peptide) tetramer, range=0.03 to 0.59%; and HLA-A2-GLCTLVAML (BMLF1 lytic antigen peptide) tetramer, range=0.06 to 0.76%. The majority of tetramer reactive cells displayed an activated/memory phenotype.Pediatric transplant recipients receiving immunosuppression can generate EBV-specific CD8+ T cells. Phenotypic and functional analysis of tetramer cells may prove useful in defining and monitoring EBV infection in the posttransplant patient.

    View details for PubMedID 12352909

  • Response to recombinant hepatitis B vaccine in children and adolescents with chronic renal failure AMERICAN JOURNAL OF KIDNEY DISEASES Watkins, S. L., Alexander, S. R., Brewer, E. D., Hesley, T. M., West, D. J., Chan, I. S., Mendelman, P., Bailey, S. M., Burns, J. L., Hogg, R. J. 2002; 40 (2): 365-372


    Diminished antibody responses to the dosage of hepatitis B (HB) vaccine indicated for healthy adults has led to a greater dosage recommendation (40 microg of HB surface antigen [HBsAg]) for adults with chronic renal failure (CRF), but an appropriate dosage for children with CRF has not been established.Seventy-eight children and adolescents with CRF (22 patients, predialysis; 42 patients, chronic dialysis therapy; 14 renal transplant recipients) aged 1 to 19 years (mean, 10.1 years) were enrolled onto a study to test a three 20-microg dose course of the HB vaccine Recombivax HB (Merck & Co, Inc, West Point, PA).The vaccine was well tolerated; no patient had a serious adverse event attributable to vaccine, and no patient withdrew from the study because of an adverse event. Overall, 91% of 66 patients administered three doses had a protective titer of 10 mIU/mL or greater for antibody against HBsAg (anti-HBs) and a geometric mean titer (GMT) of 733 mIU/mL, with seroprotection rates and GMTs among predialysis, dialysis, and renal transplant patients of 100% (4,140 mIU/mL), 94% (419 mIU/mL), and 64% (152 mIU/mL), respectively. All (100%) predialysis patients had a 10-mIU/mL or greater anti-HBs titer after only two doses of vaccine compared with 64% of dialysis patients and 50% of transplant recipients. Eighty-eight percent of 57 fully vaccinated patients tested 12 months after the first dose retained a 10-mIU/mL or greater anti-HBs titer.A regimen of three 20-microg doses of Recombivax HB is suitably immunogenic for children with CRF not administered immunosuppressive medication. When possible, at least two, and preferably all three, doses of vaccine should be administered before progression to end-stage renal disease.

    View details for DOI 10.1053/ajkd.2002.34521

    View details for Web of Science ID 000177129800018

    View details for PubMedID 12148110

  • Late post-transplant anemia in adult renal transplant recipients. An under-recognized problem? AMERICAN JOURNAL OF TRANSPLANTATION Yorgin, P. D., Scandling, J. D., Belson, A., Sanchez, J., Alexander, S. R., Andreoni, K. A. 2002; 2 (5): 429-435


    Post-transplant anemia (PTA), a frequent complication during the first 3-6 months after transplant, is thought to be uncommon during the late post-transplant period. A study population of adults (> 18 years) transplanted during 1995 at Stanford University (n = 88) and University of North Carolina (n = 40) was selected. Data-collection points were 0, 1, 2, 3, 4 and 5 years post transplant. Anemia was defined as a hematocrit < 33 volume percentage. Thirty percent of patients were anemic at some time during the post-transplant period. The prevalence of PTA increased over time; by 5 years post transplant, 26% of the patients were anemic. Anemia occurred in 62.5% of patients converted from azathioprine to mycophenolate mofetil. A multivariate logistic regression model demonstrated a correlation between anemia and serum total CO2 (p = 0.002), BUN (p = 0.04), and creatinine (p = 0.045) at 1 year post transplant. At 5 years post transplant, only serum total CO2 (p = 0.0004) correlated with anemia. Thus, diminished renal excretory function and metabolic acidosis appear to be the most important correlates of late PTA. These findings should be interpreted in view of the fact that the newer immunosuppressive agents may have an even more profound effect on anemia and its recovery after transplantation.

    View details for Web of Science ID 000176143200006

    View details for PubMedID 12123208

  • Pancreas after kidney transplantation JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Hariharan, S., Pirsch, J. D., Lu, C. Y., Chan, L., Pesavento, T. E., Alexander, S., Bumgardner, G. L., Baasadona, G., Hricik, D. E., Pescovitz, M. D., Rubin, N. T., Stratta, R. J. 2002; 13 (4)

    View details for Web of Science ID 000174627700035

    View details for PubMedID 11912273

  • Type 1 diabetes mellitus and epilepsia partialis continua in a 6-year-old boy with elevated anti-GAD65 antibodies PEDIATRICS Olson, J. A., Olson, D. M., Sandborg, C., Alexander, S., Buckingham, B. 2002; 109 (3)


    A 6-year-old boy presented with epilepsia partialis continua 6 months after diagnosis of type 1 diabetes. Anti-glutamic acid decarboxylase 65 antibodies were found in his serum and cerebrospinal fluid. Anti-epileptic agents did not improve his seizures. High-dose steroids, plasmapheresis, and intravenous immunoglobulin resulted in decreased anti-glutamic acid decarboxylase 65 antibody levels and resolution of his seizures.

    View details for Web of Science ID 000174202800012

    View details for PubMedID 11875178

  • Long-term plasmapheresis and protein A column treatment of recurrent FSGS PEDIATRIC NEPHROLOGY Belson, A., Yorgin, P. D., Al-Uzri, A. Y., Salvatierra, O., Higgins, J., Alexander, S. R. 2001; 16 (12): 985-989


    Transient or intermittent plasmapheresis with concurrent immunosuppressive therapy is thought to be beneficial in the treatment of recurrent focal segmental glomerulosclerosis (FSGS) in the early post-transplant period. The results of long-term (6-year) plasmapheresis therapy, in a 9-year-old female with an immediate recurrence of FSGS [urinary protein/urinary creatinine (UP/UC)=17.7] after cadaveric renal transplant, are presented. A 4-week plasmapheresis course induced a decline in the proteinuria, but a relapse occurred after cessation of plasmapheresis. Addition of protein A column therapy led to a further decrease in the proteinuria, to a non-nephrotic range. Long-term control of the nephrotic syndrome was established using a chronic treatment regimen consisting of a single-volume plasmapheresis, followed by a protein A column treatment, performed on sequential days every 3-4 weeks. Mean UP/UC values decreased to 1.15+/-0.9. A course of cyclophosphamide was successfully used to control a worsening of proteinuria 4 years post transplant. Although sequential renal biopsies demonstrated progressive glomerular sclerosis, the patient's mean calculated creatinine clearance only modestly declined from 78.3 ml/min per 1.73 m2, at the time of transplantation, to 62.7 ml/min per 1.73 m2, 6 years later. This patient demonstrated dependence on plasmapheresis/protein A column therapy to maintain a clinical remission of her FSGS recurrence. While long-term plasmapheresis and protein A column therapy in combination with immunosuppressive therapy reversed the effects of uncontrolled nephrosis and possibly facilitated long-term renal allograft survival, the glomerular sclerosis continued to progress.

    View details for Web of Science ID 000173174300008

    View details for PubMedID 11793085

  • The clinical efficacy of higher hematocrit levels in children with chronic renal insufficiency and those undergoing dialysis SEMINARS IN NEPHROLOGY Yorgin, P. D., Belson, A., Al-Uzri, A. Y., Alexander, S. R. 2001; 21 (5): 451-462


    The optimal hematocrit target range in children with end-stage renal disease, who are receiving recombinant human erythropoietin, is ambiguous due to the lack of compelling, age-appropriate studies. There are a large number of adult and pediatric studies which show that physical performance as well as morbidity and mortality are positively influenced by partial normalization of the hematocrit to 30 vol% to 36 vol%. Cognition studies performed in adults similarly show improvement with partial correction of hematocrit. Normalization of hematocrit studies show lower mortality rates, incremental further improvement in cognition, and greater resolution of cardiac anomalies when compared with patients with partial correction of anemia. Conversely, cardiac death rates may increase in adult patients receiving hemodialysis with preexisting cardiac disease, and there are concerns about the effect of recombinant human erythropoietin on catheter/shunt/fistula patency and on blood pressure. The high cost of recombinant human erythropoietin and established Medicare and Dialysis Outcomes Quality Initiative target hematocrit ranges have also influenced pediatric nephrologists in their assessment of the risk-benefit ratios, despite new adult data suggesting that maintenance of higher hematocrits may be cost-effective. The rationale of using adult-derived hematocrits in children with end-stage renal disease needs to be re-examined in the context of the unique growth and developmental requirements of children. A prospective, multicenter study which determines the relative benefits and risks of age-adjusted hematocrit normalization in children with renal failure is warranted.

    View details for Web of Science ID 000171005800004

    View details for PubMedID 11559886

  • Recurrence of hemolytic uremic syndrome after renal transplantation in children - A report of the North American Pediatric Renal Transplant Cooperative Study TRANSPLANTATION Quan, A., Sullivan, E. K., Alexander, S. R. 2001; 72 (4): 742-745


    Hemolytic uremic syndrome (HUS) is the cause of renal failure in 2-4% of children on dialysis. After renal transplantation, HUS can recur, but recurrence rate and risk factors are controversial.We reviewed the recurrence of HUS within the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry and used a separate questionnaire to ascertain additional clinical information.Of 68 renal allografts, HUS recurred in 6 allografts (8.8%) occurring in five patients (8.2%). Four patients had atypical HUS, whereas one patient had classic HUS. HUS recurred after transplantation in 33 days or less in all but one allograft. Outcome was poor with five of six allografts lost, despite treatment with fresh-frozen plasma or plasmapheresis. Cyclosporine had no effect on outcome or HUS recurrence.The risk of HUS recurrence in the allograft is 8-9% and is heightened in atypical HUS. Treatment was not effective and graft outcome was poor. Cyclosporine does not affect HUS recurrence.

    View details for Web of Science ID 000170968400033

    View details for PubMedID 11544443

  • Promising early outcomes with a novel, complete steroid avoidance immunosuppression protool in pediatric renal transplantation TRANSPLANTATION Sarwal, M. M., Yorgin, P. D., Alexander, S., Millan, M. T., Belson, A., Belanger, N., Granucci, L., MAJOR, C., Costaglio, C., Sanchez, J., Orlandi, P., Salvatierra, O. 2001; 72 (1): 13-21


    Corticosteroids have been a cornerstone of immunosuppression for four decades despite their adverse side effects. Past attempts at steroid withdrawal in pediatric renal transplantation have had little success. This study tests the hypothesis that a complete steroid-free immunosuppressive protocol avoids steroid dependency for suppression of the immune response with its accompanying risk of acute rejection on steroid withdrawal.An open labeled prospective study of complete steroid avoidance immunosuppressive protocol was undertaken in 10 unsensitized pediatric recipients (ages 5-21 years; mean 14.4 years) of first renal allografts. Steroids were substituted with extended daclizumab use, in combination with tacrolimus and mycophenolate mofetil. Protocol biopsies were performed in the steroid-free group at 0, 1, 3, 6, and 12 months posttransplantation. Clinical outcomes were compared to a steroid-based group of 37 matched historical controls.Graft and patient survival was 100% in both groups. Clinical acute rejection was absent in the steroid-free group at a mean follow-up time of 9 months (range 3-13.7 months). Protocol biopsies in the steroid-free group (includes 10 patients at 3 months, 7 at 6 months, and 4 at 12 months) revealed only two instances of mild (Banff 1A) subclinical rejection (reversed by only a nominal increase in immunosuppression) and no chronic rejection. At 6 months the steroid-free group had no hypertension requiring treatment (P=0.003), no hypercholesterolemia (P=0.007), and essentially no body disfigurement (P=0.0001). Serum creatinines, Schwartz GFR, and mean delta height Z scores trended better in the steroid-free group. In the steroid-free group, one patient had cytomegalovirus disease at 1 month and three had easily treated herpes simplex stomatitis, but with no significant increase in bacterial infections or rehospitalizations over the steroid-based group. The steroid-free group was more anemic early posttransplantation (P=0.004), suggesting an early role of steroids in erythrogenesis; erythropoietin use normalized hematocrits by 6 months.Complete steroid-free immunosuppression is efficacious and safe in this selected group of children with no early clinical acute rejection episodes. This protocol avoids the morbid side effects of steroids without increasing infection, and may play a future critical role in avoiding noncompliance, although optimizing renal function and growth.

    View details for PubMedID 11468528

  • Pulse methylprednisolone, cyclosporine, and ACE inhibitor therapy decreases proteinuria in two siblings with familial focal segmental glomerulosclerosis AMERICAN JOURNAL OF KIDNEY DISEASES Yorgin, P. D., Belson, A., Higgins, J., Alexander, S. R. 2001; 37 (6)


    Familial focal segmental glomerulosclerosis (FSGS) is a heterogeneous renal disease characterized by proteinuria and an unremitting deterioration of renal excretory function. Previous studies showed corticosteroid unresponsiveness and a variable response to cyclophosphamide therapy. We hypothesized that treatment with pulse methylprednisolone therapy (PMT), alternate-day corticosteroids, and cyclosphosphamide or cyclosporine would decrease proteinuria in patients with familial FSGS. Two adolescent brothers, 13 and 16 years old, presented with nephrotic range proteinuria, but with normal renal excretory function. Both brothers had renal biopsies that showed FSGS with mesangial hypercellularity and tubular atrophy. Intravenous PMT, at doses of 1 g, was initiated per the Tune-Mendoza protocol. Both patients received lisinopril therapy. One brother (case 1) was treated with PMT, alternate-day corticosteroids, and cyclophosphamide (total cumulative cyclophosphamide dose was 154.3 mg/kg). Urinary protein-to-urinary creatinine (UP/UC) ratios decreased from 6.79 to 3.79. Cyclosporine therapy decreased the UP/UC further from 2.48 to 0.76 at the end of PMT. The other brother (case 2), treated with PMT, alternate-day corticosteroids, and cyclosporine, experienced a decrease in UP/UC from 7.27 to 1.14. At the time of last evaluation, approximately 7 months after the last PMT dose, the UP/UC ratios were 0.27 (case 1) and 0.37 (case 2). PMT-attributable adverse effects were not severe. Both patients continued to receive oral cyclosporine and lisinopril after completion of PMT. PMT and cyclosporine therapy may reduce proteinuria, without decreasing renal excretory function, in some patients with familial FSGS. Further evaluation of cyclosporine therapy and PMT of patients with familial FSGS is warranted.

    View details for DOI 10.1053/ajkd.2001.24544

    View details for Web of Science ID 000169729400001

    View details for PubMedID 11382715

  • Loss of living donor renal allograft survival advantage in children with focal segmental glomerulosclerosis KIDNEY INTERNATIONAL Baum, M. A., Stablein, D. M., Panzarino, V. M., Tejani, A., Harmon, W. E., Alexander, S. R. 2001; 59 (1): 328-333


    Because of concerns of increased risk of graft loss with recurrent disease, living donor (LD) transplantation in children with focal segmental glomerulosclerosis (FSGS) has been controversial.The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database from January 1987 to January 2000 was examined to determine differences in demographics, treatment, and outcomes in children with FSGS compared with other renal diseases.Data on 6484 children, 752 (11.6%) with FSGS, demonstrated that FSGS patients were more likely to be older and black, and were less likely to receive either pre-emptive or LD transplant (P < 0.001). No differences existed in human lymphocyte antigen (HLA) matching or immunosuppression regimens. Acute tubular necrosis occurred in more FSGS patients following LD (11.8 vs. 4.6%) or cadaveric (CD; 27.9 vs. 16.3%) transplants (P < 0.001). Graft survival was worse for LD FSGS patients (5 years 69%) compared with no FSGS (82%, P < 0.001) and was not significantly different than CD graft survival in the FSGS (60%) and No FSGS groups (67%). The LD to CD ratios of relative risk of graft failure were higher in FSGS patients (test for interaction, P = 0.01). Recurrence of original disease was the only cause of graft failure that differed between groups (P < 0.001). A greater percentage of LD FSGS graft failures was attributed to recurrence (P = 0.06).The impact of FSGS on graft survival in children is greatest in LD transplants, resulting in loss of expected LD graft survival advantage. The rationale for LD grafts in children with FSGS should be based on factors other than better outcomes typically associated with LD transplantation.

    View details for Web of Science ID 000166294700037

    View details for PubMedID 11135087

  • Sodium ferric gluconate therapy in renal transplant and renal failure patients PEDIATRIC NEPHROLOGY Yorgin, P. D., Belson, A., Sarwal, M., Alexander, S. R. 2000; 15 (3-4): 171-175


    Intravenous infusion of sodium ferric gluconate (Ferrlecit) has been reported to be effective and safe in pediatric and adult hemodialysis patients with iron depletion. We sought to expand on the previous studies by treating 13 consecutive pediatric renal failure and renal transplant patients with sodium ferric gluconate doses that were higher than previously reported. Efficacy was defined as: (1) an increase in hematocrit of > or = 3 vol% with no change or a decrease in erythropoietin dose or (2) a stable hematocrit with a decrease of > or = 25% in the erythropoietin, 2 weeks to 2 months after sodium ferric gluconate infusion. Two dosing strategies were employed: (1) high dose, where single dose sodium ferric gluconate (mg) approximately calculated iron deficit, and (2) sodium ferric gluconate, 62.5 mg/dose for children < 40 kg, 125 mg/dose for children > 40 kg, infused on eight consecutive hemodialysis runs. There was only one self-limited adverse reaction in 60 doses. Three patients with previous adverse reactions to iron dextran tolerated sodium ferric gluconate without adverse effect. Sodium ferric gluconate was efficacious in eight out of ten patients that received a cumulative dose > 5 mg/kg. The mean hematocrit increased 30.3 +/- 7.8 to 36.4 +/- 4.4 vol% (P = 0.04) and the mean erythropoietin dose decreased 251.5 +/- 149.1 to 100.7 +/- 113.0 units/kg/week (P = 0.02). Although sodium ferric gluconate appears to be effective and safe at the doses used, multicenter, prospective pharmacokinetic and clinical trials of sodium ferric gluconate should be conducted in children.

    View details for Web of Science ID 000165758800002

    View details for PubMedID 11149105

  • Consensus guidelines for the treatment of peritonitis in pediatric patients receiving peritoneal dialysis PERITONEAL DIALYSIS INTERNATIONAL Warady, B. A., Schaefer, F., Holloway, M., Alexander, S., Kandert, M., Piraino, B., Salusky, I., Tranaeus, A., Divino, J., Honda, M., Mujais, S., Verrina, E. 2000; 20 (6): 610-624

    View details for Web of Science ID 000166707100006

    View details for PubMedID 11216549

  • A 100% 2-year graft survival can be attained in high-risk 15-kg or smaller infant recipients of kidney allografts 71st Annual Session of the Pacific-Coast-Surgical-Association Millan, M. T., Sarwal, M. M., Lemley, K. V., Yorgin, P., Orlandi, P., So, S., Alexander, S., Salvatierra, O. AMER MEDICAL ASSOC. 2000: 1063–68


    Infants make up the most high-risk, difficult to care for subgroup undergoing kidney transplantation, with the lowest 1- and 2-year graft survival rates of any other age group. The principal causes of graft loss have been graft thrombosis, primary nonfunction, technical error, and irreversible acute rejection.Infants undergoing kidney transplantation can achieve near 100% graft survival at 2 years following surgery, despite their very high-risk status.Analysis of 45 consecutive kidney transplants performed in patients weighing less than or equal to 15 kg during an 8-year period beginning August 1991. Patients included complex referrals from throughout the United States and all received transplants and were cared for by the same pediatric kidney transplantation team.Mean weight at transplantation was 11. 2 kg. Renal failure was due to congenital or urologic causes in the majority (53%) of cases. Size-discrepant adult-sized kidney grafts were transplanted in 80% of patients; 64% received live-donor grafts; 78% were receiving dialysis prior to transplantation; and 27% had extremely small bladders (<20 cm(3)) requiring modification of the ureteral implantation. Excluding 1 transplant-unrelated death, graft and patient survival at 2 years was 100%. Eight-year patient and graft survival rates (for our combined live and cadaver donor series) were 89.6% and 84.6%, respectively. This compares favorably with much lower graft survival in low-risk adult recipients. Delayed graft function occurred in only 1 patient (2%). Rate of incidence of rejection was 9.3% within 2 years of transplantation and the overall rejection rate was 15.5%. No graft was lost to vascular thrombosis, primary nonfunction, technical error, or acute rejection. The mean creatinine level was 53.04 micromol/L (0.6 mg/dL) and 61.9 micromol/L (0.7 mg/dL) at 1 and 2 years, respectively, and 88.4 micromol/L (1.0 mg/dL) at 3, 4, and 5 years after transplantation.One hundred percent 2-year and excellent 8-year graft survival rates can be achieved in what has historically been the highest-risk and most difficult to care for patient subgroup undergoing kidney transplantation.

    View details for PubMedID 10982511

  • The trials and tribulations of an adolescent patient with end-stage renal disease PERITONEAL DIALYSIS INTERNATIONAL Alexander, S. R., Warady, B. A., Shooter, M. 2000; 20 (2): 247-258

    View details for Web of Science ID 000086859900021

    View details for PubMedID 10809257

  • Predictive factors for delayed graft function (DGF) and its impact on renal graft survival in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatric transplantation Tejani, A. H., Sullivan, E. K., Alexander, S. R., Fine, R. N., Harmon, W. E., Kohaut, E. C. 1999; 3 (4): 293-300


    We define delayed graft function (DGF) as the need for dialysis during the first post-transplant week. We analyzed 5272 transplants, of which 2486 were of living donor (LD) and 2786 were of cadaver donor (CD) origin. Twelve per cent (620/5272) of all patients developed DGF. Donor specific rates were 5.6% for LD and 19.1% for CD patients. Factors predictive of DGF in CD patients were: African-American race (25%), prolonged cold ischemia (24%), absence of T-cell induction antibody therapy and absence of HLA-DR matching. The relative risk (RR) for graft failure due to DGF was 6.02 (p < 0.001) in LD patients and 2.58 (p < 0.001) for CD recipients. Two-year graft survival (GS) in LD patients without DGF was 89.6%, compared to 41.6% for those with DGF (p < 0.001); in CD patients it was 80.2% and 49.5%, respectively (p < 0.001). Censoring for primary non-function, GS for LD patients with a functioning graft at 30 d post-transplant and no DGF was 91.5%, compared to 70.1% for those with DGF (p < 0.001); GS for CD patients was 83.8% and 68.7%, respectively (p < 0.001). However, when patients whose grafts had failed during the first year were censored no differences in GS were noted between patients with and without DGF for either LD or CD recipients. To determine whether DGF acts as an independent risk factor for graft failure, patients were segregated into four groups: rejection with DGF; rejection without DGF; DGF without rejection; and no DGF, no rejection. When these groups were compared DGF emerged as an independent risk factor for graft failure. This large study reviewing pediatric renal transplantation over 10 yr clearly delineates the role of DGF as a major risk factor for graft failure.

    View details for PubMedID 10562974

  • A new, unique and simple method for ureteral implantation in kidney recipients with small, defunctionalized bladders TRANSPLANTATION Salvatierra, O., Sarwal, M., Alexander, S., Lemley, K. V., Yorgin, P., Al-Uzri, A., Lu, A., MILLAN, M., Alfrey, E. 1999; 68 (6): 731-738


    Major, almost insurmountable, deterrents exist to the use of the small capacity, defunctionalized, nonneurogenic urinary bladder in renal transplantation, namely, the technical difficulty in performing a satisfactory ureteral implantation with conventional methods and the potential secondary problems with high grade ureteral reflux and obstruction. Alternatives are less than ideal and include transplantation into a bowel-augmented urinary bladder with intermittent self-catheterization, ileal conduit urinary diversion, or avoidance of transplantation and relegating the patient to life-long dialysis.Eight consecutive patients (ages 13 months to 29 years) with small, defunctionalized urinary bladders underwent a new method of intravesical implantation of the transplant ureter. The mean capacity of these bladders was 18.5+/-13.1 ml (range 6 to 45 ml), with the bladders defunctionalized for a mean 81.6+/-24.3% of the patients' total lifetime. The technique involved placement of the transplant ureter into a shallow, mucosa-denuded, rectangular trough extending from a superiorly placed ureteral hiatus distally to the trigone. We hypothesized that the mucosal margins on the two lateral aspects of the rectangular trough would grow over the anterior surface of the ureter until they met the advancing mucosal edges from the contralateral side to form a natural neosubmucosal tunnel.Posttransplantation cystoscopic examination demonstrated bladder mucosal regeneration and growth over the ureter, confirming the spontaneous development of a good length neosubmucosal tunnel. All patients demonstrated no evidence of ureteral reflux or ureteral obstruction, whereas an immediate prior cohort of four consecutive patients with bladder capacities < or =30 ml showed that three of four had ureteral reflux (P=0.02) and four of four developed hydronephrosis (P=0.002). All urinary bladders in the present cohort enlarged to expected normal or nearnormal capacities. Serum creatinines were stable throughout the entire follow-up period, with the exception of one patient who had rejection episodes. Two patients had urinary tract infections posttransplantation, but there were no episodes of acute pyelonephritis.This novel technique for ureteral implantation successfully capitalizes on the regenerative potential of the bladder mucosa, resulting in a physiological, anatomically natural, and very effective neosubmucosal tunnel. It appears to guarantee success against both ureteral reflux and obstruction, no matter how small the urinary bladder, and offers no hindrance to enlarging the bladder to near normal capacity posttransplantation. The implantation technique is simple and safe, and its use should eliminate the reluctance to use these bladders. Moreover, this procedure offers a major incentive for the successful rehabilitation of small, defunctionalized, nonneurogenic bladders after kidney transplantation.

    View details for PubMedID 10515372

  • Chronic dialysis in children and adolescents - The 1996 Annual Report of the North American Pediatric Renal Transplant Cooperative Study PEDIATRIC NEPHROLOGY Lerner, G. R., Warady, B. A., Sullivan, E. K., Alexander, S. R. 1999; 13 (5): 404-417


    The 1996 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes data submitted from 130 centers on 2,208 patients in whom 2,787 independent courses of dialysis were performed between 1 January 1992 and 16 January 1996. Approximately two-thirds of the dialysis population were maintained on peritoneal dialysis (PD), with automated PD remaining the preferred modality. There were 964 episodes of peritonitis in 1,018 patient years, yielding an overall peritonitis rate of 1 episode every 13 patient months. More PD patients attended school full time than hemodialysis (HD) patients at baseline (77% vs. 45%), which continued at 6, 12, and 24 months of followup. There were fewer Hispanic patients who were full-time students, whether on HD or PD, compared with white or black patients; 18% of Hispanic patients did not attend school, even though they were medically capable. The majority of dialysis courses terminated due to transplantation (54%), with change in dialysis modality the next most-common reason (28%). Early dialysis termination for any reason was seen more often in HD than PD (40% vs. 23% at 6 months), but by 24 months similar percentages of PD and HD courses had been terminated (75% HD, 72% PD). The most-common PD access was a Tenckhoff catheter with a single cuff, a straight tunnel and lateral exit site. The majority of HD accesses were external percutaneous catheters, with the sublcavian vein the most-common site. Erythropoietin was administered in 93% of HD and PD patients at 24 months.

    View details for Web of Science ID 000080989800006

    View details for PubMedID 10412861

  • Daclizumab (zenapax) in pediatric renal allografts: Final data Nevins, T., Ettenger, R., Potter, D., Pescovitz, M., Knechtle, S., Colombani, P., Alexander, S., Ramos, E. LIPPINCOTT WILLIAMS & WILKINS. 1999: S124–S124
  • Optimal care of the pediatric end-stage renal disease patient on dialysis AMERICAN JOURNAL OF KIDNEY DISEASES Warady, B. A., Alexander, S. R., Watkins, S., Kohaut, E., Harmon, W. E. 1999; 33 (3): 567-583


    This manuscript is an effort on behalf of the American Society of Pediatric Nephrology to provide recommendations designed to optimize the clinical care of pediatric patients with end-stage renal disease (ESRD). Although many of the recommendations are evidenced-based with the supporting data being derived from a variety of sources, including patient registries, others are opinion-based and derived from the combined clinical experience of the authors. In all cases, it is recommended that the decision to initiate dialysis should be made only after an assessment of a combination of biochemical and clinical characteristics. Irrespective of the choice of dialysis modality (hemodialysis v peritoneal dialysis), dialysis efficacy should be measured regularly, and the dialysis prescription should be designed to achieve target clearances. Attention to dialysis adequacy, control of osteodystrophy, nutrition, and correction of anemia is mandatory, because all may influence patient outcome in terms of growth, cognitive development, and school performance. Finally, the availability of a multidisciplinary team of pediatric specialists is desirable to provide all facets of pediatric ESRD care, including renal transplantation, in an optimal manner. Future clinical research efforts intended to address topics such as dialysis adequacy, anemia management, and growth should be encouraged.

    View details for Web of Science ID 000078878400020

    View details for PubMedID 10070923

  • Transplantation of adult-sized kidneys into infants induces major blood flow changes XVIIth World Congress of the Transplantation-Society Salvatierra, O., Singh, T., Shifrin, R., Conley, S., Alexander, S., Tanney, D., Lemley, K., Sarwal, M., Mackle, F., Alfrey, E., Orlandi, P., Zarins, C., Herfkens, R. ELSEVIER SCIENCE INC. 1999: 236–37

    View details for PubMedID 10083090

  • Steady improvement in short-term graft survival of pediatric renal transplants: the NAPRTCS experience. Clinical transplants Tejani, A., Stablein, D. M., Donaldson, L., Harmon, W. E., Alexander, S. R., Kohaut, E., Emmett, L., Fine, R. N. 1999: 95-110


    This report of pediatric renal transplantation covers the years 1987-1998. Since its inception in 1987, the NAPRTCS has collected data on 6,038 transplants performed in 5,516 patients provided by 73 renal centers across the country. FSGS, together with developmental lesions of dysplasia and obstructive uropathy, account for 40% of all transplants. There has been a steady increase in the use of LD donors among children with 54% of all transplants in 1996 and 1997 being live-related. About 72% of LD transplants are performed in Caucasian children, with African-American children unfortunately receiving a disproportionate percentage of CD kidneys. There has been a steady decline in the use of CD kidneys recovered from young individuals and a gradual decline in the number of transplants performed in young recipients (< 6 years old). Graft survival for LD recipients was 91%, 84% and 79% at one, 3 and 5 years, respectively, and the comparative figures for CD recipients were 81%, 72% and 64%, respectively. Acute and chronic rejections account for most of the graft losses, with chronic rejection accounting for more than 30%. There has been a steady improvement in one-year graft survival of CD recipients with the 1997-1998 cohort exhibiting an improvement of 16% over the 1987-1988 cohort. This improvement has been brought about by eliminating the use of infant donor kidneys, reducing the number of random transfusions and increasing the maintenance dose of cyclosporine. Posttransplant growth continues to be poor, with catch-up growth being exhibited only in children under age 6.

    View details for PubMedID 11038628

  • The impact of donor source, recipient age, pre-operative immunotherapy and induction therapy on early and late acute rejections in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatric transplantation Tejani, A. H., Stablein, D. M., Sullivan, E. K., Alexander, S. R., Fine, R. N., Harmon, W. E., Kohaut, E. C. 1998; 2 (4): 318-324


    Acute rejection is a frequent event in pediatric transplantation. In addition to graft loss, acute rejection episodes stimulate the development of chronic rejection and inhibit growth in children post-transplantation. In this study, we analyzed our data from 1987 through 1996 to identify acute rejection episodes in children. In 2,520 living donor (LD) transplants there were 2,540 rejection episodes (rejection ratio: 1.1), and in 2,579 cadaver donor (CD) transplants 3,653 episodes were observed (rejection ratio: 1.32). For LD recipients the first rejection occurred sooner when there was at least one HLA-DR mismatch (RR=1.6, p<0.001) and prophylactic T-cell antibody was not used (RR=1.4, p<0.001). For CD transplants absence of prophylactic T-cell antibody (RR=1.2, p<0.001) and donor age below five years were risk factors (RR=1.5, p<0.001). Late initial acute rejections were seen in 327 of 1,471 patients (22.2%) who were rejection free at one year. At risk for the development of late rejections were children over the age of six years at transplantation (RR=1.7, p<0.001) and children of non-white origin (RR=1.5, p <0.002). For LD transplant recipients in the age range of 0-5 years, irreversible rejection was observed in 8.7% compared to 4.1% for older children (RR=1.46, p<0.001). Similar results for CD transplants were 12.6% versus 6.6% (RR=1.5, p<0.00). The high frequency of rejection episodes in children and the greater irreversibility in younger children suggest pediatric patients may have a more robust immune response. Current ongoing studies in the molecular mechanisms of the pathogenesis of rejection in surveillance biopsies of children may help determine if this hypothesis is valid.

    View details for PubMedID 10084737

  • Successful transplantation of adult-sized kidneys into infants requires maintenance of high aortic blood flow TRANSPLANTATION Salvatierra, O., Singh, T., Shifrin, R., Conley, S., Alexander, S., Tanney, D., Lemley, K., Sarwal, M., Mackie, F., Alfrey, E., Orlandi, P., Zarins, C., Herfkens, R. 1998; 66 (7): 819-823


    Nationally, results of renal transplantation in infants are inferior to those in older children and adults. Within the infant group, best results are obtained with adult-sized kidneys (ASKs) rather than size-compatible pediatric kidneys. However, transplantation of ASKs into infants has an increased risk of acute tubular necrosis and graft loss from vascular thrombosis and primary nonfunction. The aim of this study was to define and understand the hemodynamic changes induced by ASK transplantation, so that outcomes of transplantation in infants can be improved.Nine hemodynamically stable and optimally hydrated infants were studied under a controlled sedation with cine phase-contrast magnetic resonance at three time periods: before transplantation, 8-12 days after transplantation, and 4-6 months after transplantation. Cross-sectional images of both the infant aorta and the adult transplant renal artery were obtained and blood flow was quantitated. Renal volumes were also obtained, and expected renal artery blood flow based on early posttransplant volume was calculated. In addition, renal artery blood flow was determined in 10 in situ native adult kidneys prior to donor nephrectomy. Supplemental nasogastric or gastrostomy tube feeding was carried out during the blood flow study period to optimize intravascular volume.Mean infant aortic blood flows were 331+/-148 ml/min before transplantation, 761+/-272 ml/ min at 8-12 days after transplantation (P=0.0006 with pretransplant flow), and 665+/-138 ml/min at 4-6 months after transplantation (P=0.0001 with pretransplant flow). Mean transplanted renal artery flows were 385+/-158 ml/min at 8-12 days and 296+/-113 ml/min at 4-6 months after transplantation. Transplanted renal artery flows were less than prenephrectomy in situ donor renal artery blood flow (618+/-130 ml/min; P=0.02 and P=0.0003) and expected normal renal artery blood flow (666+/-87 ml/min; P=0.003 and P=0.001) at both 8-12 days and 4-6 months after transplantation. A 26% reduction in renal volume (P=0.003) occurred between the two postoperative time periods, and this paralleled the decrease in posttransplant renal artery flow. One-year graft and patient survival in the nine infants was 100%. The mean serum creatinine levels at 3, 6, and 12 months were 0.43+/-0.10, 0.48+/-0.15, and 0.49+/-0.16 mg/dl.This study is the first to quantitatively document the blood flow changes occurring after ASK transplantation in infants. There was a greater than two-fold increase in aortic blood flow after ASK transplantation, and this increase was sustained for at least 4 months and appeared to be driven by the blood flow demand of the ASK. However, actual posttransplant renal artery blood flow was significantly less than normal renal artery flow. Our study suggests that aggressive intravascular volume maintenance may be necessary to achieve and maintain optimum aortic blood flow, so as not to further compromise posttransplant renal artery flow and to avoid low-flow states that could induce acute tubular necrosis, vascular thrombosis, or primary nonfunction.

    View details for PubMedID 9798687

  • Glomerular filtration rate in children following renal transplantation. Pediatric transplantation Seikaly, M. G., Browne, R., Simonds, N., Atkins, C., Alexander, S. R. 1998; 2 (3): 231-235


    Most studies evaluating renal function post-renal transplantation in children have used serum creatinine (S(Cr)) or estimates of its clearance (C(SCH)). When renal function is impaired both S(Cr) and the C(SCH) overestimate glomerular filtration rate (GFR), especially during cyclosporine therapy. This study measured GFR in 64 children (age range: 4-19 years) with stable renal function who received renal allografts at the Childrens Medical Center of Dallas, 31 from live related donors (LRD) and 33 from cadaveric donors (CAD). 125I-iothalamate clearance (C(IO)) was used as the reference standard for measuring GFR. Data from 100 C(IO) studies, were analyzed and results reported as mean +/- S.E.M. C(IO) performed during the first year after renal transplantation in 23 children who received allografts from LRD was 72.4+/-5.5 ml/min per 1.73 m2 compared to 50.4+/-7.4 ml/min per 1.73 m2 in 18 children who received allografts from CAD (p<0.05). Beyond the first year post-renal transplantation there was no difference in C(IO) between LRD and CAD allografts. When S(Cr) was compared to C(IO), the relationship was nonlinear. C(IO) was also compared to the simultaneous estimation of creatinine clearance by C(SCH). The overestimation of GFR by C(SCH) was inversely proportional to the level of renal function. When renal function was normal or mildly reduced (C(IO) > 50 ml/min per 1.73 m2), C(SCH) closely approximated C(IO). When renal function was moderately to severely curtailed (C(IO) < or = 50 ml/min per 1.73 m2), C(SCH) overestimated C(IO) by 43.6+/-5.6%. The study concludes that in children with renal transplant: 1) C(IO) is higher in allografts from LRD compared to CAD kidneys only in the first 12 months following renal transplantation; 2) S(Cr) is a poor predictor of C(IO); and 3) C(SCH) consistently overestimates GFR children following renal transplantation unless renal function is normal or only mildly decreased.

    View details for PubMedID 10084748

  • Pediatric renal transplantation: indications and special considerations. A position paper from the Pediatric Committee of the American Society of Transplant Physicians. Pediatric transplantation Davis, I. D., Bunchman, T. E., Grimm, P. C., Benfield, M. R., Briscoe, D. M., Harmon, W. E., Alexander, S. R., Avner, E. D. 1998; 2 (2): 117-129


    Renal transplantation of children with chronic renal insufficiency (CRI) and end-stage renal disease (ESRD) appears to be the optimal form of renal replacement therapy. This report, which expresses the opinions of the nephrology members of the Pediatric Committee of the American Society of Transplant Physicians, discusses the indications for pediatric renal transplantation and identifies the unique aspects of caring for children with CRI and ESRD. Indications for pediatric renal transplantation include: 1) symptoms of uremia not responsive to standard therapy; 2) failure to thrive due to limitations in total caloric intake; 3) delayed psychomotor development; 4) hypervolemia; 5) hyperkalemia; and 6) metabolic bone disease due to renal osteodystrophy. The urgency and timing of renal transplantation in children must be considered in the context of a number of issues unique to children with CRI and ESRD such as delayed cognitive and educational performance, growth retardation, delayed puberty, etiology of ESRD, and timing of immunizations. In addition, these children frequently display various inherited and sporadic syndromes with multiorgan involvement requiring the expertise of a variety of pediatric subspecialists including the pediatric urologist, who plays a critical role in the evaluation of children with obstructive uropathy and other anomalies of the genito-urinary system. The advantages of a living-related donor are also delineated. The importance of adequate immunosuppression on graft function, early recognition of the signs and symptoms acute rejection, preventive strategies for minimizing the morbidity and mortality from viral infections in the post-transplant period, and the impact of transplantation on cognitive function, educational status, and catch-up growth are also discussed. To address these complex issues, transplant care of pediatric patients must be provided by a multidisciplinary team of pediatric health care professionals.

    View details for PubMedID 10082443

  • Pediatric Transplant Grand Rounds. Pediatric kidney transplantation at Stanford. Pediatric transplantation Salvatierra, O., Alexander, S. R., KRENSKY, A. M. 1998; 2 (2): 165-176


    (1) We believe that we have achieved excellent graft survival with pediatric kidney transplantation because: (a) we have had no technical losses; (b) there have been no primary immunologic losses within 4 years following transplantation; (c) we have avoided ATN. (2) Our cyclosporine dosage has been greater than the average dosage reported by the NAPRTCS, and we believe that this has led to: (a) a low incidence of rejection episodes; (b) because of this, good 1 and 2 year average serum creatinine levels. (3) In the management of adult-sized kidneys in infants and small children I have discussed: (a) the rationale and strategy to prevent vascular thrombosis, ATN and primary non-function; (b) the importance of optimizing intravascular volume, as well as renal and aortic blood flow. (4) With regard to the management of congenital urologic abnormalities I have discussed: (a) the strategy to avoid unnecessary surgery and to avoid scar around the aorta and the vena cava, particularly in infants and small children; (b) my philosophy regarding the abnormal bladder and the successful use of the small defunctionalized urinary bladder. We believe that these have been the primary ingredients to the success we have seen. I also harken back and continue to practice the adage advanced by my former mentor Dr. Fred Belzer that 'no kidney is better than a bad kidney!' And this could not be more true than in pediatric kidney transplantation, where graft failure enhanced by suboptimal graft quality may potentially both cripple the child and shorten his/her life.

    View details for PubMedID 10082451

  • ABO-mismatched renal transplantation in children: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) and the Midwest Organ Bank (MOB). Pediatric transplantation Osorio, A. V., Sullivan, E. K., Alexander, S. R., Bryan, C. F., Shield, C. F., Warady, B. A. 1998; 2 (1): 26-29


    Successful ABO-mismatched renal transplantation (RT) (blood group A2 donor to blood group B or O recipient) has occurred in adults in the setting of a low titer (< or =4) natural isoagglutinin (anti-A) level in the recipient of the mismatched organ. Similar experiences have rarely occurred in children. Between 1986-1996, 11 pediatric patients (6 male and 5 female) received 11 ABO-mismatched kidneys [7 cadaveric (CAD) and 4 living related donor (LRD)]. There were 8 O recipients/A2 donor pairs, 2 B recipients/A2 donor pairs and 1 B recipient/A2B donor pair. Recipient age at the time of RT was 14.7+/-3.0 yr (mean +/- SD). Prior to RT, 2 recipients underwent splenectomy and none received donor-specific transfusions. Induction and early maintenance immunosuppression consisted of corticosteroids (11 pts), ALG/ATG (6 pts), OKT3 (3 pts), azathioprine (11 pts) and cyclosporine (8 pts). The mean 30-d cyclosporine dosage was 10.6+/-4.0 mg/kg/d. Eight patients suffered > or =1 acute rejection episodes, the initial episode occurring within the first 31 d post-transplant in 7 of them. Five grafts (45.4%) failed secondary to vascular thrombosis (1), acute rejection (2) and chronic rejection (2). The remaining grafts (54.5%) all functioned for >1000 d (range: 1023-3746 d). The pre-transplant anti-A titer was determined in 6 pts; in 4 it was low (2) and in 2 it was high (8). Graft survival in all but one of these patients (whose titer was 8 and who suffered a non-rejection-related vascular thrombosis) was > or =2 yr. In summary, ABO-mismatched RT in pediatric patients is an uncommon practice. However, the adult experience and our preliminary pediatric experience suggests that evaluation of recipient isoagglutinin levels in this setting may be helpful in the selection of donor/recipient pairs in whom mismatched transplantation can be successful.

    View details for PubMedID 10084756

  • Peritoneal catheters and exit-site practices toward optimum peritoneal access: 1998 update (Official report from the international society for peritoneal dialysis) PERITONEAL DIALYSIS INTERNATIONAL Gokal, R., Alexander, S., Ash, S., Chen, T. W., Danielson, A., Holmes, C., Joffe, P., Moncrief, J., Nichols, K., Piraino, B., Prowant, B., Slingeneyer, A., STEGMAYR, B., Twardowski, Z., Vas, S. 1998; 18 (1): 11-33

    View details for Web of Science ID 000072488100002

    View details for PubMedID 9527026

  • NKF-DOQI clinical practice guidelines for hemodialysis adequacy AMERICAN JOURNAL OF KIDNEY DISEASES Eknoyan, G., Levin, N. W., Owen, W., Roberts, J., Alexander, S., Cohen, D., Harmon, W., Ing, T., Kari, J., Keen, M., King, K., Letteri, J., Teehan, B., Tzamaloukas, A., Warady, B. 1997; 30 (3): S17-S63
  • NKF-DOQI clinical practice guidelines for peritoneal dialysis adequacy AMERICAN JOURNAL OF KIDNEY DISEASES Eknoyan, G., Levin, N. W., Owen, W., Roberts, J., Alexander, S., Cohen, D., Harmon, W., Ing, T., Kari, J., Keen, M., King, K., Letteri, J., Teehan, B., Tzamaloukas, A., Warady, B. 1997; 30 (3): S69-S133
  • Growth rates in pediatric dialysis patients and renal transplant recipients AMERICAN JOURNAL OF KIDNEY DISEASES Turenne, M. N., Port, F. K., Strawderman, R. L., Ettenger, R. B., Alexander, S. R., Lewy, J. E., Jones, C. A., Agodoa, L. Y., Held, P. J. 1997; 30 (2): 193-203


    We compared growth rates by modality over a 6- to 14-month period in 1,302 US pediatric end-stage renal disese (ESRD) patients treated during 1990. Modality comparisons were adjusted for age, sex, race, ethnicity, and ESRD duration using linear regression models by age group (0.5 to 4 years, 5 to 9 years, 10 to 14 years, and 15 to 18 years). Growth rates were higher in young children receiving a transplant compared with those receiving dialysis (ages 0.5 to 4 years, delta = 3.1 cm/yr v continuous cycling peritoneal dialysis [CCPD], P < 0.01; ages 5 to 9 years, delta = 2.0 to 2.6 cm/yr v CCPD, chronic ambulatory peritoneal dialysis (CAPD), and hemodialysis, P < 0.01). In contrast, growth rates in older children were not statistically different when comparing transplantation with each dialysis modality. For most age groups of transplant recipients, we observed faster growth with alternate-day versus daily steroids that was not fully explained by differences in allograft function. Younger patients (<15 years) grew at comparable rates with each dialysis modality, while older CAPD patients grew faster compared with hemodialysis or CCPD patients (P < 0.02). There was no substantial pubertal growth spurt in transplant or dialysis patients. This national US study of pediatric growth rates with dialysis and transplantation shows differences in growth by modality that vary by age group.

    View details for Web of Science ID A1997XQ78300005

    View details for PubMedID 9261029

  • Renal transplantation, chronic dialysis, and chronic renal insufficiency in children and adolescents. The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study PEDIATRIC NEPHROLOGY Warady, B. A., Hebert, D., Sullivan, E. K., Alexander, S. R., Tejani, A. 1997; 11 (1): 49-64


    The 1995 Annual Report of the North American Pediatric Renal Transplant Cooperative Study summarizes data voluntarily collected from 123 centers on 5,197 children and adolescents grouped into three cohorts: (1) patients who received renal transplants on or after 1 January 1987 (n = 3,066), (2) patients who were maintained on peritoneal dialysis (PD) or hemodialysis (HD) on or after 1 January 1992 (n = 1,488), and (3) patients treated for chronic renal insufficiency (CRI) on or after 1 January 1994 (n = 643). The transplant and dialysis information update previous registry data whereas the CRI information reflects 1st-year registry data. Three-year graft survival rates were 83% and 66% for living donor grafts and cadaver donor (CD) grafts, respectively. Triple drug maintenance therapy with prednisone, cyclosporine, and azathioprine was used by > 70% of all transplant recipients through 5 years of follow-up. The 2-year CD survival has steadily improved from 65% in 1987 to 82% in 1992. Fifty malignancies have been reported, the majority of which are lymphoproliferative disorders. The 2-year patient survival posttransplantation is 95%. Mortality rates for the youngest patients have drastically improved over the past 2 years. Approximately two-thirds of patients in the dialysis cohort are maintained on PD; automated PD remains the preferred modality. Overall, the peritonitis rate is one infection every 13.3 patient months, the frequency of infection being greatest in the youngest patients. Whereas the primary reason for dialysis modality termination is transplantation approximately 40% of the entire dialysis cohort (PD at HD) were not considered active transplant candidate Baseline CRI data revealed the most common primary diagnoses to be obstructive uropathy (24%) and aplastic/hypoplastic/dysplastic kidneys (19%). The standardized height deficit in the CRI cohort was greatest in the younger patients and those with the most impaired renal function.

    View details for Web of Science ID A1997WE95500013

    View details for PubMedID 9035173

  • Pediatric renal transplantation--the NAPRTCS experience. Clinical transplants Tejani, A. H., Sullivan, E. K., Harmon, W. E., Fine, R. N., Kohaut, E., Emmett, L., Alexander, S. R. 1997: 87-100


    The NAPRTCS has enrolled 4,329 children who have received an index renal transplant since 1987. Seventy-three percent of the transplant recipients were children above 6 years of age. In the age group below 6 years rejection episodes are not more frequent, however the first acute rejection episode is frequently irreversible leading to graft failure. Many of the renal disorders that lead to ESRD and transplantation in adults, such as diabetes and hypertension, are less often observed in the pediatric population. Developmental disorders, such as renal dysplasia and obstructive uropathy, are frequent diagnostic entities, and the most common glomerular disorder leading to transplantation in children is focal segmental glomerulosclerosis. In an attempt to overcome dialysis-associated growth retardation many pediatric renal centers resort to preemptive transplantation, thus 24% of the children receiving a transplant have never undergone dialysis. Graft survival in these children is similar to that observed in children receiving maintenance dialysis, however accelerated growth is not noted. Catch-up growth, defined as gain of 1 SDS, is observed in 47% of children below the age of 6 years and in only 22% of children over the age of 6 years. Infants (below 2 years) have a higher mortality rate following transplantation compared to older children. Long-term (5-year) graft survival for children receiving a cadaver donor graft is 60%, and for living donor kidney recipients the graft survival is 76%. Due to changes in practice patterns, such as a judicious use of cadaver donors, increased use of prophylactic T-cell antibody, and better maintenance immunosuppression, cadaver donor graft survival has improved each year since 1987. The cohorts of children with a cadaver donor transplant in the years 1991 and 1992 have a 2-year graft survival which is 10% better than that observed in the earlier years.

    View details for PubMedID 9919393

  • Peritoneal dialysis workshop: pediatrics recommendations. Peritoneal dialysis international Alexander, S. R., Salusky, I. B., Warady, B. A., Watkins, S. L. 1997; 17: S25-7

    View details for PubMedID 9304653

  • Peritoneal membrane transport function in children receiving long-term dialysis JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Warady, B. A., Alexander, S. R., HOSSLI, S., Vonesh, E., Geary, D., Watkins, S., Salusky, I. B., Kohaut, E. C. 1996; 7 (11): 2385-2391


    Accurate characterization of peritoneal solute transport capacity in children has been hampered by a lack of standardized test mechanics and small patient numbers. A standardized peritoneal equilibration test was used to study 95 pediatric patients (mean age, 9.9 +/- 5.6 yr) receiving chronic peritoneal dialysis at 14 centers. Patients were divided into four age groups (< 1, 1 to 3, 4 to 11, 12 to 19 yr) for analysis. Each patient received a 4-h peritoneal equilibration test with an exchange volume of 1100 mL/m2 per body surface area. Dialysate to plasma (D/P) ratios for creatinine (C) and urea (U) and the ratio of dialysate glucose (G) to initial dialysate glucose concentration (D/D0) were determined. Mass transfer area coefficients (MTAC) were calculated for the three solutes and potassium (P). The mean (+/- SD) 4-h D/P ratios for C and U were 0.64 +/- 0.13 and 0.82 +/- 0.09, respectively. The mean 4-h D/D0 for G was 0.33 +/- 0.10. D/P and D/D0 ratio results were similar across age groups. Normalized (for body surface area) mean MTAC (+/- SD) values were as follows: C, 10.66 +/- 3.74; G, 12.93 +/- 5.02; U, 18.43 +/- 4.02; and P, 14.02 +/- 3.94. Whereas a comparison of the normalized MTAC values across age groups with an analysis of variance showed significant age group differences only for glucose (P = 0.001) and potassium (P = 0.036), analysis by quadratic regression demonstrated a nonlinear decrease with age for C (P = 0.016), G (P < 0.001), and P (P = 0.034). In summary, evaluation of D/P and D/D0 ratios obtained from a large group of children in a standardized manner reveals values that are similar across the pediatric age range and not unlike the results obtained in adults. In contrast, normalized MTAC values of young children are greater than the values of older children, possibly as a result of maturational changes in the peritoneal membrane or differences in the effective peritoneal membrane surface area.

    View details for Web of Science ID A1996VV35900015

    View details for PubMedID 8959629

  • Peritoneal dialysis-related peritonitis treatment recommendations: 1996 update PERITONEAL DIALYSIS INTERNATIONAL Keane, W. F., Alexander, S. R., Bailie, G. R., Boeschoten, E., Gokal, R., Golper, T. A., Holmes, C. J., Huang, C. C., Kawaguchi, Y., Piraino, B., Riella, M., Schaefer, F., Vas, S. 1996; 16 (6): 557-573


    The recommendations provided in this document represent a distillation of various experiences, as well as data obtained from published studies in the setting of substantial changes in antibiotic sensitivity. It is hoped that this revised compilation will provide a basis upon which future developments and advances can be made in the therapeutic approach to infectious complications of peritoneal dialysis.

    View details for Web of Science ID A1996WC19800006

    View details for PubMedID 8981523

  • Use of neoral in pediatric renal transplantation 1st International Cybercongress - Transplantation in the next Millennium: A Landmark in Organ Transplantation Technology Ettenger, R. E., Smith, H. T., Kaiser, B., Cooney, G. F., Summerauer, J., Alexander, S., MOULTON, L. T., Choc, M. G., Wong, R. L. ELSEVIER SCIENCE INC. 1996: 2257–58

    View details for Web of Science ID A1996VD46300082

    View details for PubMedID 8769217

  • (125)Iodine-iothalamate clearance in children. A simple method to measure glomerular filtration PEDIATRIC NEPHROLOGY Bajaj, G., Alexander, S. R., Browne, R., Sakarcan, A., Seikaly, M. G. 1996; 10 (1): 25-28


    Glomerular filtration rate (GFR) is the most widely used test to evaluate renal function. Several clearance markers have been used to measure GFR in adults. In children, however, a simple and reliable method to measure GFR is not available. Renal 125iodine (I)-iothalamate clearance, after a single subcutaneous injection, is a simple and accurate test to measure GFR in adults. The validity of unlabelled iothalamate, as a marker for measurement of GFR in children, was reported recently. Unfortunately, the unlabelled iothalamate assay is arduous. We report our experience with a single subcutaneous injection of 125I-iothalamate to measure GFR in normal children and those with renal disease. A weight-adjusted dosing regimen was adopted. This regimen resulted in sufficient above-background radioactivity in both blood and urine for reproducible measurement of GFR. Intra-test variability for GFR was not affected by the degree of renal insufficiency. The test was well tolerated with only 2 patients developing mild headache during the procedure. Our study showed that renal clearance of 125I-iothalamate is reproducible, simple, and practical in healthy children and those with mild and advanced renal disease.

    View details for Web of Science ID A1996TV34200007

    View details for PubMedID 8611350

  • Lessons from the peritoneal dialysis patient database: a report of the North American Pediatric Renal Transplant Cooperative Study. Kidney international. Supplement Warady, B. A., Sullivan, E. K., Alexander, S. R. 1996; 53: S68-71


    Data derived from 1383 independent courses of peritoneal dialysis have been recorded in the database of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Automated peritoneal dialysis (APD) continues to be the preferred modality. Peritoneal access is most commonly achieved with a Tenckhoff curled catheter with a single-cuff and straight tunnel. Overall, the peritonitis rate is 1 infection every 13.3 months, the frequency of infection being greatest in the youngest patients. Two-cuffed catheters and exit-sites directed down positively influence this rate. Excessive infection is the primary reason for modality termination in surviving patients not transplanted. A total of 64 deaths have occurred in the peritoneal dialysis population. The 12-month and 24-month mortality probabilities in children < two years of age are significantly greater than comparable data in the older children.

    View details for PubMedID 8770994

  • Lessons from the peritoneal dialysis patient database: A report of the North American Pediatric Renal Transplant Cooperative Study 5th Annual North American Pediatric Renal Transplantation Cooperative Study Warady, B. A., Sullivan, E. K., Alexander, S. R. BLACKWELL SCIENCE INC. 1996: S68–S71
  • Chylous ascites complicating neonatal peritoneal dialysis PEDIATRIC NEPHROLOGY Melnick, J. Z., McCarty, C. M., Hunchik, M. P., Alexander, S. R. 1995; 9 (6): 753-755


    We report the development of chylous ascites in a neonate as an uncommon complication during continuous peritoneal dialysis. Cloudy dialysis fluid containing many white blood cells might confuse the diagnosis of chylous ascites with infective peritonitis and result in inappropriate use of antibiotics. Resolution may be critical, since chyle removal during dialysis may result in profound immunosuppression and malnutrition due to lymphocyte and fat losses. After 4 weeks on a modified diet, the chyle leak resolved. The patient returned to breast milk and continues nighttime continuous-cycle peritoneal dialysis without further chyle leak.

    View details for Web of Science ID A1995TM16100019

    View details for PubMedID 8747121



    From 1987 through 1994, the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) has enrolled 1641 cadaver donor transplants. For this study, we have analyzed one and two year graft survival by annual cohorts for the years 1987 through 1991. For the 1987 cohort one and two year graft survival was 72% and 65%, respectively, and for the 1991 cohort it was 83% and 78%, respectively. Using a proportional hazards model, and comparing the 1987 cohort to the 1991 cohort, the relative risk for graft failure was 1.40 (P = 0.02). Analysis of practice patterns revealed the following changes which may have been associated with this improved graft survival: (1) use of T cell induction antibody, 38% in 1987 and 67% in 1991 (P < or = 0.001); (2) the increased use of cyclosporine (CsA) post-transplant: in 1987, 87% were maintained on CsA at day 30 compared to 97% in 1991 (P < 0.001); (3) the mean higher daily maintenance CsA dose at 12 months post-transplant which in 1987 was 6.5 mg/kg compared to 7.5 mg/kg in 1991 (P = 0.03); (4) the decreased use of random transfusions, 54% receiving > 5 transfusions in 1987 compared to 37% in 1991 (P < 0.001); and (5) decreased use of younger cadaver donors between 1987 and 1991 (P < 0.001).

    View details for Web of Science ID A1995RK81000028

    View details for PubMedID 7564125



    A multicenter study was conducted to determine the relationship between intraperitoneal volume and solute (e.g., urea, creatinine) transport as determined by the dialysate to plasma (D/P) ratio and mass transfer area coefficient (MTAC). Two 4-h peritoneal equilibration tests were conducted on each of 12 pediatric peritoneal dialysis patients (mean age, 10.8 yr; range, 0.2 to 19.2 yr). One test exchange volume was 900 mL/m2 body surface area (BSA), and the other was 1,100 mL/m2 BSA. Dialysate samples were collected at 0, 30, 60, 120, 180, and 240 min. Blood samples were drawn at 0 and 240 min. Solute equilibration was significantly more rapid with the 900 mL/m2 BSA exchange volume than with the 1,100 mL/m2 exchange volume when evaluated by the D/P ratio. In contrast, no differences in solute transport were noted with either exchange volume when assessed with the MTAC. In conclusion, solute D/P ratios vary with changes in the intraperitoneal volume, necessitating the use of a standardized exchange volume for the reliable interpretation of evaluations such as the peritoneal equilibration tests. In contrast, the use of the MTAC allows for an accurate assessment of solute transport over a wide range of exchange volumes.

    View details for Web of Science ID A1995QX38000011

    View details for PubMedID 7620091

  • ANALYSIS OF REJECTION OUTCOMES AND IMPLICATIONS - A REPORT OF THE NORTH-AMERICAN PEDIATRIC RENAL-TRANSPLANT COOPERATIVE STUDY 13th Annual Meeting of the American-Society-of-Transplant-Physicians Tejani, A., Stablein, D., Alexander, S., Fine, R., Harmon, W. WILLIAMS & WILKINS. 1995: 500–504


    For this study, we analyzed the role of rejection in graft failure in children. Rejection results were examined after 3004 pediatric renal transplants (1367 living donor, 1637 cadaver source). A total of 3453 (1298 living donor, 2155 cadaver source) rejection episodes have occurred, for rejection ratios of .95 for living donor and 1.32 for cadaver source transplants, with a constant difference of 18% points after four months, in the percentage of patients ever experiencing a rejection. Rejection results were examined by patient age (0-1 vs. 2-5 vs. 6-12 vs. > or = 13). Rejection ratios, annualized rejection frequency, time to first rejection, and mean number of rejections for patients with rejection were not elevated in the younger patients. However, for the initial rejection episode, recipients less than six years of age had significantly (P < .001) poorer outcome from the rejection episode with an increased risk of graft failure in both donor source groups. This age effect on rejection outcome is only seen with the first rejection episode and is not observed with subsequent rejection episodes.

    View details for Web of Science ID A1995QK22500010

    View details for PubMedID 7878753

  • THE EVALUATION OF CANDIDATES FOR RENAL-TRANSPLANTATION - THE CURRENT PRACTICE OF US TRANSPLANT CENTERS 12th Annual Meeting of the American-Society-of-Transplant-Physicians Ramos, E. L., Kasiske, B. L., Alexander, S. R., Danovitch, G. M., Harmon, W. E., Kahana, L., KIRESUK, T. J., Neylan, J. F. LIPPINCOTT WILLIAMS & WILKINS. 1994: 490–97


    The criteria for acceptance of candidates for renal transplantation varies throughout the United States. The Patient Care and Education Committee of the American Society of Transplant Physicians conducted a survey of all U.S. centers that participate in the United Network for Organ Sharing (UNOS) concerning their evaluation of adult candidates for kidney transplantation. The response to each question was examined according to the specialty of the individual who filled out the questionnaire, as well as the type of transplant center (university or private) and the size of the center. The response rate to the survey was 81% (147/182). We found the following: (1) university-based and larger centers accepted more medically complicated patients; (2) 83% noted that attendance to dialysis was an important indicator of compliance after transplantation; (3) 79% did not require preoperative blood transfusions for cadaver kidney recipients; (4) 66% set no specific upper age limit for transplantation; (5) 56% excluded patients with chronic active hepatitis in the setting of hepatitis B antigenemia; (6) 50% had no specific policy for evaluating hepatitis C antibody-positive patients, while 54% excluded the use of hepatitis C antibody-positive donors, and (7) 15% obtained coronary angiography on all diabetic patients. U.S. transplant centers have a heterogeneous approach to the evaluation of patients for renal transplantation, particularly in the areas of viral hepatitis, cardiovascular disease, and noncompliance. University-based centers and centers that perform a larger number of transplants accept more medically complicated patients.

    View details for Web of Science ID A1994MZ32800002

    View details for PubMedID 7509515

  • POSTTRANSPLANT DEATHS AND FACTORS THAT INFLUENCE THE MORTALITY-RATE IN NORTH-AMERICAN CHILDREN 12th Annual Meeting of the American-Society-of-Transplant-Physicians Tejani, A., Sullivan, E. K., Alexander, S., Fine, R., Harmon, W., Lilienfeld, D. LIPPINCOTT WILLIAMS & WILKINS. 1994: 547–53


    Of 2457 patients in the North American Pediatric Renal Transplant Cooperative Study registry who were followed for 5481 patient-years after the index transplantation, we observed 136 deaths, for an average annual rate of 24.8 deaths per 1000 patient-years. Death resulted primarily from infection (n = 55, 40%), cardiovascular causes (n = 28, 21%), hemorrhage (n = 16, 12%), and malignancies (n = 9, 7%). Cadaver-donor source was associated with greater mortality (6.7%) than a living-donor source (4.0%) (P < 0.005). Recipients aged 0-1, 2-5, 6-12, and 13-17 years old had mortality rates of 17.5, 8.0, 3.6, and 4.5%, respectively (P < .001). Mortality rates increased substantially when examined by recipient and cadaver donor ages (mortality rates of up to 45%), the greater the concordance between young donor and recipient ages. Interestingly, acute tubular necrosis and graft failure less than 30 days after transplantation (GH30) were each associated with markedly elevated mortality rates. (The risk ratio for ATN was 3.1 [P < 0.001] and for GF30 it was 6.4 [P < 0.001].) Mortality after transplantation was also affected by the underlying renal disease, with high mortality rates observed for oxalosis (n = 21, 33.3%), congenital nephrotic syndrome (n = 79, 15.2%), pyelo/interstitial nephritis (n = 54, 11.1%), and Drash syndrome (n = 14, 21.4%). When the joint effect of these risk factors was examined in a Cox proportional hazards model, young recipient age (0-1 years old) and GF30 were significant (P < .001) risk factors of mortality for recipients of living-donor organs. For recipients of cadaver kidneys, young recipient age--0-1 years old (P < .001) and 2-5 years old (P = .002)--ATN (P = .029), and GF30 (P < .001) were all significant risk factors. Recipient age is the major determinant of increased mortality after renal transplantation. Avoidance of acute tubular necrosis by reducing cold time and preventing early graft failure by better matching techniques in this vulnerable population may improve the mortality rate.

    View details for Web of Science ID A1994MZ32800013

    View details for PubMedID 8116040



    From January 1987 to January 1992 the North American Pediatric Renal Transplant Cooperative Study registered and followed 2,037 children and adolescents 17 years of age or less who received 2,197 renal transplants at 75 participating centers in the United States and Canada. The cumulative experience over 5 years of data collection demonstrated trends in renal transplantation practice for pediatric patients. The percentage of live donor organ recipients receiving donor-specific blood transfusions decreased from 40% in 1987 to less than 12% in 1991; random blood transfusions also were used less frequently during the most recent 2 years of the study. Immunosuppressive therapy on posttransplant day 0 or 1 with polyclonal and monoclonal antilymphocyte agents was used in over 40% of transplants. There was also a notable preference for the combined use of prednisone, azathioprine and cyclosporine as maintenance immunosuppression. The percentage of live donor source graft recipients receiving cyclosporine increased from 78% in 1987 to 90% in the most recent year, and considered together, nearly 90% of live donor and cadaver organ recipients received cyclosporine. The observed graft survival probabilities for live donor grafts were 88%, 83%, 81% and 76% at years 1-4 post transplantation, respectively. The 1st through 4th year graft survival probabilities for cadaver grafts were 74%, 68%, 63% and 58%, respectively. The five most common causes of pediatric end-stage renal disease have remained as: hypoplastic-dysplastic kidney, obstructive uropathy, focal segmental glomerulosclerosis, reflux nephropathy and systemic immunological diseases throughout the 5 years of this study. There has been a decrease in children 2 years of age or less undergoing transplant surgery. On average, 50% of graft failures were due to the various forms of rejection. Vascular thrombosis (14%) and recurrence of primary renal disease (7%) were the next most frequently encountered causes of graft failure. Poor linear growth was identified as a problem affecting the majority of children both before and after transplantation. Post transplant linear growth was best among recipients less than 6 years of age at transplantation and recipients of all ages who received alternate-day prednisone. A total of 16 malignancies were reported during the 5 years of study. A total of 105 deaths were reported, with infection (41%) the most common primary cause of death. The 2-year patient survival probabilities were 95.5% and 93% for recipients of live donor and cadaver grafts, respectively.

    View details for Web of Science ID A1993MP18300005

    View details for PubMedID 8130089

  • Maintenance dialysis in North American children and adolescents: a preliminary report. North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Kidney international. Supplement Alexander, S. R., Sullivan, E. K., Harmon, W. E., Stablein, D. M., Tejani, A. 1993; 43: S104-9


    During 1992 the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) began to develop a pediatric Dialysis Patient Data Base by collecting data on pediatric patients who had received either hemodialysis (HD) or peritoneal dialysis (PD), or both, at a participating NAPRTCS center. This preliminary report describes study methods and contains detailed, though short-term observations reported by 64 of 87 NAPRTCS centers on 762 patients who were < 21 years of age at enrollment and who received treatment between January 1, 1992 and September 15, 1992. In these 762 patients, a total of 810 independent courses of dialysis therapy were identified (PD = 534 [65.9%]; HD = 276 [34.1%]). Patients age groupings showed a significantly greater proportion of PD patients among younger age groups. Automated peritoneal dialysis was used by about 75% of registered PD patients at one and six months after registration. A total of 196 peritonitis episodes were reported, yielding a peritonitis rate of one episode every 7.1 patient-months. Ten percent of PD catheters were replaced, primarily for mechanical malfunction and leaks. Percutaneous catheters were used for vascular access in about one-half of the HD patients, with the remainder almost equally divided between arteriovenous fistulae and grafts. Vascular access revision was reported in 28% of HD patients, with about one-third of these revisions performed to create a more permanent access. Recombinant human erythropoietin therapy was used in 89% of PD and 94% of HD patients at six months. Recombinant human growth hormone therapy was used in 9% of PD and 5% of HD patients at six months.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for PubMedID 8246361

  • PROCEEDINGS OF A SYMPOSIUM ON AN UPDATE ON CYTOMEGALOVIRUS-INFECTION IN SOLID-ORGAN TRANSPLANTATION - MAY 17-19, 1993 HOUSTON, TEXAS - CASE-HISTORY ROUND-TABLE DISCUSSION TRANSPLANTATION PROCEEDINGS Finn, W., Aeder, M., Alexander, S., Brennan, S., Butt, K. M., Ettenger, R., Greenstein, S., Harford, A., Harmon, W. E., Heifets, M., Hull, D., Jordan, M. L., Martin, M., Shapiro, R., Uber, L. A., UBER, W. A., Waid, T. H., West, J. C. 1993; 25 (5): 30-40


    The North American Pediatric Renal Transplant Cooperative Study collects extensive data on all transplants entered into its registry. For this study we evaluated 568 cadaver kidney and 492 live-donor recipients with graft function at 30 days post transplant. Utilizing maintenance immunosuppressive therapy at 30 days post transplant, we evaluated patient and graft outcome, mortality and morbidity over the first 6 months post transplant. For cadaver kidney recipients, 36 patients were receiving prednisone and azathioprine (PA), 114 were maintained on prednisone and cyclosporine (PC) and 418 were on prednisone, cyclosporine and azathioprine (PCA). Patients receiving PA had a greater incidence of rejection prior to 30 days, a greater incidence of hospitalization for rejection and for hypertension over the next 6 months and a greater loss of allograft in the first 6 months compared with the other two groups. The only difference noted between PC and PCA was a lower serum creatinine in the PCA group at 6 months. For living-related kidney recipients, there were 78 patients maintained on PA, 97 on PC and 317 on PCA. Again patients receiving PA had a higher rate of hospitalization for rejection and a higher rate of graft loss. When patients receiving PC were compared with those receiving PCA, no differences were noted in the 6-month serum creatinine values, but a greater percentage of PCA patients were receiving antibiotics on day 30. We conclude that PA is poor therapy for both groups, PCA is ideal therapy for cadaver kidney recipients, but no beneficial effects are noted when PCA is used over PC for live-related donor kidney transplants.

    View details for Web of Science ID A1993KT23100003

    View details for PubMedID 8476703



    To ascertain growth and rehabilitation of children after transplantation, the North American Pediatric Renal Transplant Cooperative Study collected growth data on renal transplant recipients. From January 1987 through December 1990, a total of 1553 children with one or more transplants were entered into the study by its 75 participating centers. Of these, the first 300 children with a functioning graft and 2 years of linear growth data form the cohort for this study. For the total cohort of 300 patients, the mean (+/- SEM) baseline height z score was -2.41 +/- 0.09, and the change in z score determined after 2 years was 0.18 +/- 0.06 (p < 0.01). Children in the age group from birth to 1 year had the maximal deficit and had the maximal improvement in z score, gaining about 1 SD (p < 0.01). For the 2- to 5-year-old group, the change in z score was about 0.5 SD (p < 0.001). No improvement in z score was noted for children 6 to 17 years of age. Each increase in serum creatinine concentration of 90 mumol/L (1 mg/dl) was associated with -0.17 decrease in the z score (p < 0.001). Gender, donor source, history of previous transplantation, and prior dialysis were not associated with a significant change in the z score; thus the increased rate of growth during the first 2 post-transplantation years occurred mainly in subjects less than 6 years of age.

    View details for Web of Science ID A1993KQ59200011

    View details for PubMedID 8441094

  • Continuous peritoneal dialysis for children: a decade of worldwide growth and development. Kidney international. Supplement Alexander, S. R., Honda, M. 1993; 40: S65-74


    This review surveys the dramatic worldwide expansion of the use of continuous peritoneal dialysis as maintenance renal replacement therapy for children with end-stage renal disease that has occurred during the past decade. Before 1982, fewer than 100 pediatric patients had been treated with continuous ambulatory peritoneal dialysis (CAPD), and continuous cycler peritoneal dialysis (CCPD) for children was virtually unknown. By the end of 1989 CAPD/CCPD was accounting for 50% of pediatric dialysis patients (less than 15 years old) in the United States, 65% in Canada, and 75% in Australia/New Zealand. Growth of CAPD/CCPD for children in Europe overall has been less spectacular, but there is wide variability from country to country, with CAPD/CCPD concentrated in eight member countries of the European Dialysis and Transplant Association. Several of these countries (notably the United Kingdom, Israel, the Netherlands and the former Federal Republic of Germany) were treating 46% to 70% of pediatric patients with CAPD/CCPD by the end of 1987. Other European countries such as France and Spain showed little growth of CAPD/CCPD over the decade (10% to 20% of patients treated with CAPD/CCPD). In Japan, CAPD for children has just begun, but because Japanese children are likely to spend longer periods on dialysis awaiting transplantation, information on long-term use of CAPD/CCPD in children may be forthcoming from Japan in the future. No effort is made to compare CAPD/CCPD to hemodialysis as a maintenance therapy for children. The advantages of CAPD/CCPD for the young patient, especially the infant and very young child are noted, and from the past decade of dramatic worldwide growth of CAPD/CCPD in pediatric patients it is inferred that the majority of children, (from 50% to 75%) can be successfully treated with these modalities, at least for the short-term (that is, several years), while awaiting transplantation.

    View details for PubMedID 8445841


    View details for Web of Science ID A1993KZ62000017

    View details for PubMedID 8494940



    Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the effect of donor age on graft survival for pediatric recipients of cadaver donor renal transplants. Between January 1, 1987, and November 16, 1990, 787 cadaver donor renal transplants in children less than 18 years of age were registered in the study. The ages of the donors were less than or equal to 5 years in 203 transplants, between 6 and 9 years in 87, between 10 and 39 in 389, and greater than or equal to 40 years in 108. The risk of graft loss was related to donor age by a proportional hazards analysis. The ideal donor age was 20-25 years. The risk of graft loss was increased by both young and old donor age. The risk of graft loss from a neonate donor was 2.7-fold that of the ideal donor, and the risk from a 50-year-old donor was 1.8-fold that of the ideal donor. The relationship between donor age and graft survival was not affected by the age of the recipient. Cold storage time had an added impact on graft survival: grafts with cold storage time greater than 24 hr were 1.5 times more likely to fail than grafts with shorter cold storage time for all donor ages. Analysis of the causes of graft failure revealed that 9.9% of grafts from donors less than or equal to 5 years of age were lost due to vascular thrombosis, primary nonfunction, and other technical causes, compared with 4.6% in 6-9, 4.4% in 10-39, and 2.8% in greater than or equal to 40-year-old donors. We conclude that kidneys from both young and old donors are at increased risk for graft loss, and this increased risk is seen in all recipient age groups. Many of the losses from the young donors--but not older donors--may be due to technical causes. Knowledge of these risks can be used to develop strategies for optimal utilization of kidneys from young and old donors.

    View details for Web of Science ID A1992JJ75300008

    View details for PubMedID 1496535



    Extensive clinical studies have documented the effectiveness of recombinant human erythropoietin (rHuEPO) in correcting the anemia of adult dialysis patients, but the safety and efficacy of rHuEPO in children with renal anemia cannot yet be confirmed, due to the relative deficiency of reported studies involving pediatric subjects. To date, published experience with rHuEPO therapy in children has totaled 257 patients, although the majority of these reports have appeared only as abstracts. Overall experience has been favorable, with renal anemia and transfusion dependency successfully resolved in almost all pediatric patients reported. However, controlled clinical trials have not been performed, so it is not yet possible to clearly define the risks associated with rHuEPO therapy in children. Hypertension appears to occur or become worse in up to one third of treated children, but it is unclear to what extent rHuEPO therapy is accompanied by an increased risk of seizures, thrombosis of vascular access, hyperkalemia, hyperphosphatemia, or peritonitis (when administered via the intraperitoneal route). Only preliminary and somewhat conjectural recommendations can be offered regarding pediatric rHuEPO dosing, route of administration, special precautions, and adjunctive monitoring and therapy. Fortunately, a multicenter controlled clinical trial is underway that is designed to address these issues. Because the harmful effects of renal anemia are typically more profound for children than they are for adults, the benefits of rHuEPO promise to be even greater among pediatric patients. Whether rHuEPO therapy will substantially improve growth and neurologic and psychosocial development remains to be seen, but the potential is there for rHuEPO to dramatically improve the lives of children who suffer from the effects of the anemia of chronic renal failure. Other non-renal anemias that afflict pediatric patients, such as the anemia of prematurity, also may be amenable to rHuEPO therapy.

    View details for Web of Science ID A1991GK19700009

    View details for PubMedID 1928079



    To compare outcomes from pediatric intensive care in hospitals with different levels of resources.Prospective, blinded comparison of outcome and care.Tertiary (n = 3) and nontertiary (n = 71) hospitals in Oregon and southwestern Washington.All critically ill children admitted with respiratory failure and head trauma for 6 months.Severity of illness adjusted mortality rates were determined using admission day, physiologic profiles (Pediatric Risk of Mortality score) and care modalities were assessed daily. The crude mortality rate of the tertiary patients was four times higher than for the nontertiary patients (23.4% vs. 6.0%, p less than .0001). In the tertiary patients, the numbers of outcomes were accurately predicted by physiologic profiles (observed: 30 deaths and 98 survivors; predicted: 29.3 deaths and 98.7 survivors, z = -.25, p greater than .4). However, for the nontertiary patients, the number of the deaths were significantly different than predicted (observed: 20 deaths and 315 survivors; predicted: 14.4 deaths and 320.6 survivors, z = -2.08, p less than .05). The odds ratios of dying in a nontertiary vs. a tertiary facility were about 1.1, 2.3, and 8 (p less than .05) for mortality risk groups of less than 5%, 5% to 30%, and greater than 30%. Patients in tertiary facilities received more (p less than .05) invasive (e.g., arterial catheters) and complex (e.g., mechanical ventilation) care, whereas patients in nontertiary facilities received more (p less than .05) labor-intensive care (e.g., hourly vital signs).Care of the most seriously ill children in tertiary pediatric ICUs could improve their chances of survival.

    View details for PubMedID 1796932



    Data from the North American Pediatric Renal Transplant Cooperative Study were analyzed to determine the incidence and possible causes of graft thrombosis in pediatric renal transplant recipients. Between January 1987, and November 1989, 1045 renal transplants in recipients less than 18 years of age were registered in the study, including 484 living-related donor and 561 cadaver donor transplants. There were 213 graft failures (67 LRD, 146 CAD), and of these 27 were caused by thrombosis (8 LRD, 19 CAD). Thrombosis occurred in 2.6% of all transplants and accounted for 22.5% (27/120) of all graft failures that occurred in the first 60 days following transplantation. Among the LRD recipients, there were 24 graft failures in those less than 6 years of age, and 7 of these were due to thrombosis, compared to 1 thrombosis in 43 graft losses in recipients greater than 6 years (P less than 0.01). In recipients less than 6 years old, the thrombosis rate for those who received transplants without prior dialysis was 4/32 (12.5%) versus 3/109 (2.8%) with prior dialysis. Among the CAD recipients, age of the recipient did not influence graft thrombosis. Donor age, however, was strongly associated with the risk of thrombosis, as was cold storage time. Donor age and cold storage time were not independently distributed within the population, with longer cold storage times required for younger donors. Both factors, however, independently affected outcome. Other factors, including prior nephrectomy, prior transplant, center size, and use of cyclosporine were not associated with increased risk of thrombosis in LRD or CAD recipients. We conclude that graft thrombosis is an important cause of renal graft loss in children. In LRD transplants the risk of graft thrombosis is increased in recipients less than 6 years old, and preliminary data suggest that the lack of prior dialysis may be associated with thrombotic risk in these patients. CAD transplant recipients who receive grafts from young donors, particularly those with long cold storage time, are at increased risk for graft failure due to thrombosis.

    View details for Web of Science ID A1991EY48300028

    View details for PubMedID 1994535

  • THE EFFECT OF RACE ON ACCESS AND OUTCOME IN TRANSPLANTATION NEW ENGLAND JOURNAL OF MEDICINE Kasiske, B. L., Neylan, J. F., RIGGIO, R. R., Danovitch, G. M., Kahana, L., Alexander, S. R., White, M. G. 1991; 324 (5): 302-307

    View details for Web of Science ID A1991EU92200005

    View details for PubMedID 1898431

  • Treatment modality patterns and transplantation among the United States pediatric end-stage renal disease population: a longitudinal study. Clinical transplants Held, P. J., Turenne, M. N., LISKA, D. W., ZOBEL, D. L., Webb, R. L., Alexander, S. R., Jones, C. 1991: 71-85


    Between 1985 and 1988, there were 3,393 children (Medicare insured) under age 20 who began treatment for chronic ESRD. Patterns of modality use, modality switch, mortality rates, and various aspects of transplantation were analyzed for different age and incident groups of this pediatric cohort. The pediatric cohort as a whole exhibited a distinct pattern of modality use when compared to adults in general, a point evidenced most clearly by their substantially higher rates of transplantation. Furthermore, notable differences were found within the pediatric cohort when the younger than 5, 5-9, 10-14, and 15- to 19-year-old age groups were analyzed separately. Younger pediatric patients, particularly those younger than 5 years, received peritoneal dialysis as initial ESRD therapy more frequently than their older pediatric counterparts. This result would be expected given vascular access problems often associated with very young patients. In addition, those patients younger than 5 years who began RRT with some form of hemodialysis had the highest likelihood of switching to CAPD/CCPD within the first year of therapy. Conversely, older pediatric patients were most likely to begin RRT therapy with some form of hemodialysis. By day 91, slightly over half of the 15- to 19-year-old age group was utilizing center hemodialysis; the CAPD/CCPD, other peritoneal, and functioning transplant modalities each contained about 10% of the patients with the remainder falling into the death and unknown dialysis categories. The overall pattern of switching to transplantation during the first year of RRT was similar for pediatric patients initiating RRT with center hemodialysis versus peritoneal dialysis (CAPD/CCPD), but differed by age group within each dialysis type. Pediatric patients on peritoneal dialysis were somewhat more likely to receive a transplant during the first year of ESRD compared to hemodialysis, although the difference was small. Mortality rates during the first year for patients who began treatment with center hemodialysis versus CAPD/CCPD were similar. The well-documented dominance of transplantation as a method of RRT for pediatric patients was further verified by this study. Results show that transplantation was implemented rapidly during the initial months of ESRD. Nearly 50% of surviving pediatric patients had a functioning transplant at 1 year following onset and 64% at 3 years. These percentages were exceeded for the 5- to 9-year-old age group, of which 74% had a functioning graft 3 years following onset.(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for PubMedID 1820148

  • THE 1989 REPORT OF THE NORTH-AMERICAN-PEDIATRIC-RENAL-TRANSPLANT-COOPERATIVE-STUDY PEDIATRIC NEPHROLOGY Alexander, S. R., Arbus, G. S., Butt, K. M., Conley, S., Fine, R. N., Greifer, I., Gruskin, A. B., Harmon, W. E., McEnery, P. T., Nevins, T. E., Nogueira, N., Salvatierra, O., Tejani, A. 1990; 4 (5): 542-553


    This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1-5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6-12 and 12-17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.

    View details for Web of Science ID A1990DZ44800022

    View details for PubMedID 2242326



    We analyzed the results obtained with protocols for immunosuppression of pediatric recipients of haploidentical living-related renal transplants. In the donor-specific transfusion group transfusion of blood products obtained from the prospective organ donor was performed before transplantation, and at transplantation maintenance immunosuppression of azathioprine and prednisone was begun. In the cyclosporine group donor-specific transfusion was not used, and maintenance immuno-suppression of cyclosporine and azathioprine was begun 1 week before transplantation, with the addition of prednisone at transplantation. Of 24 donor-specific transfusion recipients 3 had circulating cytotoxic antibodies to the prospective donor for an incidence of 12%. There was no significant difference between groups with respect to 1-year actual patient and graft survival (100 and 89 versus 100 and 86%, respectively), 1-year mean serum creatinine level (1.1 versus 1.2 mg./dl.), rejection treatments per patient (2.5 versus 2.6) and total days hospitalized during year 1 after transplantation (27 versus 18), with donor-specific transfusion data presented first. Initial hospitalization was significantly shorter (10 versus 16 days, p less than 0.05) and the incidence of rejection crises within 3 months was significantly less (68 versus 94%, p less than 0.05) in the cyclosporine group. We believe that cyclosporine and azathioprine pre-treatment of pediatric recipients of haploidentical living-related renal transplants with the addition of prednisone at transplantation is preferable to a donor-specific transfusion protocol because there is no risk of recipient sensitization to the prospective donor, and patient and graft survival is not adversely affected.

    View details for PubMedID 2388336

  • MONOCLONAL-ANTIBODY OKT3 THERAPY IN PEDIATRIC KIDNEY-TRANSPLANT RECIPIENTS JOURNAL OF PEDIATRICS LEONE, M. R., Barry, J. M., Alexander, S. R., Melvin, T., Striegel, J., Reller, K., Henell, K. R., Kimball, J., FUNNELL, M. B., Goldstein, G., Norman, D. J. 1990; 116 (5): S86-S91


    Thirty-one pediatric patients with acute renal allograft rejection were treated with the monoclonal antibody OKT3. In 24 cases, increased doses of steroids followed by a polyclonal antithymocyte globulin were ineffective in reversing the rejection episode. Twenty-eight patients completed the prescribed minimum 10-day treatment course, with effective rejection reversal in 22. Three patients failed to complete the course of therapy: one because of leukopenia that developed after the first dose, one because of a clotted graft, and another because of symptomatic cytomegalovirus infection. The overall success rate of OKT3 for rejection reversal was 74%; however, 55% of recipients had rebound rejection, and 85% of patients had detectable anti-OKT3 antibodies after completion of the course of therapy. Ten patients were treated with a second course of OKT3, and in eight of these patients, rejection was at least temporarily reversed. The starting dose of OKT3 for second-course therapy was the same as that used during first-course therapy, but in five cases the dose was increased during the course because of inadequate therapeutic response. Seven of these patients lost their grafts a mean of 6.5 months after completion of second-course therapy. We looked for anti-OKT3 antibody in nine recipients after completion of a second treatment course and found it in all nine. Our observations regarding a second treatment course with this monoclonal antibody preparation suggest that although rejection reversal may be observed, ultimate graft survival is poor and anti-OKT3 antibody formation is enhanced.

    View details for PubMedID 2139465



    Patients receiving hemodialysis therapy risk exposure to disinfectants used to reduce bacterial burdens in hemodialysis equipment and to reprocess hemodialyzers. From April 29 through May 9, 1988, 3 patients undergoing hemodialysis treatments at a single center were exposed to dialysis fluid that was inadvertently contaminated with hydrogen peroxide (HP). All patients showed a significant decline in blood hemoglobin level and required packed red blood cell transfusions during the 11-day exposure to HP. Contamination of dialysis fluid may have been due to the inadequate rinsing of HP from the water treatment system (WTS) following its disinfection on April 27-28, 1988. The failure to check water at point-of-use stations with a sensitive enough test kit after the disinfection for HP permitted patient exposure to contaminated dialysis fluid. To prevent similar occurrences, we recommend that after each disinfection (or other modifications of the WTS), the WTS be adequately rinsed to remove potentially toxic chemicals. Dialysis center personnel need to be aware of the potential effects that each modification or disinfection of the WTS may have on the product water used.

    View details for Web of Science ID A1990DF66800005

    View details for PubMedID 2349955



    Twelve pediatric patients, aged 28 months to 17 years, received OKT3 to reverse renal allograft rejection. In 11 patients, the rejection crisis was resistant to conventional antirejection therapy with high doses of prednisone or polyclonal antithymocyte globulin. Reversal of rejection was successful in 10 patients who completed a treatment course. Because of recurring resistant rejection, five patients received a second course of OKT3, which was successful in reversing the rejection crisis in two. Among these patients, the persistence or the appearance of high levels of circulating T3 lymphocytes after initiating the second treatment course correlated with treatment failure. The immediate side effects associated with OKT3 therapy were transient and medically manageable. We conclude that this monoclonal antibody preparation is a safe and effective treatment for pediatric renal allograft in recipients experiencing rejection crisis resistant to conventional therapy. However, the potential impact of this immunosuppressive medication on long-term renal allograft survival in this patient population remains to be determined.

    View details for Web of Science ID A1987J186400007

    View details for PubMedID 3298596

  • PLASMA VITAMIN-A LEVELS IN CHILDREN ON CAPD PERITONEAL DIALYSIS BULLETIN Parrott, K. A., STOCKBERGER, R. A., Alexander, S. R., Miller, L. T., Leklem, J. E., Jenkins, R. D. 1987; 7 (2): 90-92


    The applicability of continuous arteriovenous hemofiltration (CAVH) for renal replacement therapy was evaluated in three infants and two young children with catastrophic medical and surgical illnesses. In the first four patients, CAVH was used in conjunction with either peritoneal or hemodialysis. In the fifth patient, CAVH was the sole renal replacement therapy employed; in this critically ill anuric infant, we were best able to evaluate the ability of CAVH to continuously control fluid, electrolyte, and acid-base balance, and allow the administration of adequate parenteral nutrition. The difficulties encountered were related to anticoagulation, establishment of adequate vascular access, and selection of an appropriate hemofilter for the performance of the technique. Despite the application of suction-assistance, we were unable to effectively employ a prototype pediatric hemofilter to attain a level of plasma ultrafiltration consistent with the objectives of therapy. However, we were able to effectively and safely employ an adult hemofilter for these purposes; modifications were made in the adult hemofilter system before its application in the smallest pediatric patients. Our experience suggests that, even in critically ill infants, CAVH can be successfully applied as an effective renal replacement therapy. However, further experience is required before its potential impact on patient survival can be assessed.

    View details for Web of Science ID A1986F231000014

    View details for PubMedID 3780250

  • ISSUES IN PEDIATRIC DIALYSIS AMERICAN JOURNAL OF KIDNEY DISEASES Gruskin, A. B., Alexander, S. R., Baluarte, H. J., Grupe, W. E., Harmon, W., Potter, D. E., Salusky, I. B. 1986; 7 (4): 306-311

    View details for Web of Science ID A1986C011500009

    View details for PubMedID 3962980

  • NUTRITIONAL-REQUIREMENTS FOR INFANTS WITH RENAL-FAILURE AMERICAN JOURNAL OF KIDNEY DISEASES Wassner, S. J., Abitbol, C., Alexander, S., Conley, S., Grupe, W. E., Holliday, M. A., Rigden, S., Salusky, I. B. 1986; 7 (4): 300-305

    View details for Web of Science ID A1986C011500008

    View details for PubMedID 3515910

  • A POPULATION-BASED STUDY OF HEMOLYTIC-UREMIC SYNDROME IN OREGON, 1979-1982 AMERICAN JOURNAL OF EPIDEMIOLOGY Rogers, M. F., Rutherford, G. W., Alexander, S. R., DiLiberti, J. H., Foster, L., Schonberger, L. B., Hurwitz, E. S. 1986; 123 (1): 137-142


    The authors conducted a retrospective hospital-based chart review of cases of hemolytic-uremic syndrome among children less than or equal to 18 years of age, hospitalized in Oregon during the four-year period from January 1979 to December 1982. Thirty children with hemolytic-uremic syndrome living in Oregon were hospitalized during this period, for an average annual incidence of 0.97 cases per 100,000 children. Seventy per cent of cases occurred in children under five years of age, for an incidence of 2.65 cases per 100,000 children. Twenty-seven (90%) of the 30 children were white, and 17 (57%) were female. Twenty-four (80%) had a diarrheal prodromal illness including 20 who had bloody diarrhea. Twelve children (40%) acutely required peritoneal dialysis, and two (7%) developed chronic renal failure. Three children died, for a case fatality ratio of 10%. Sixty per cent of the 30 cases occurred during the summer and early fall months. Geographic clustering was also evident. Hemolytic-uremic syndrome is a rare but endemic disease in Oregon and may occur in small clusters. Although descriptions of several large series of patients have been published, this study describes the first statewide population-based study of this syndrome.

    View details for Web of Science ID A1986AXA2400014

    View details for PubMedID 3940432

  • MONOCLONAL-ANTIBODY FOR REVERSAL OF ACUTE RENAL-ALLOGRAFT REJECTION IN PEDIATRIC-PATIENTS TRANSPLANTATION LEONE, M. R., Funnell, B., Jenkins, R. D., Alexander, S. R., Goldstein, G., Barry, J. M., Norman, D. J. 1985; 40 (5): 574-577

    View details for Web of Science ID A1985ATZ3000022

    View details for PubMedID 3904097



    A mother and daughter with Campylobacter jejuni-associated hemolytic-uremic syndrome (HUS) are discussed. The mother was hospitalized with bloody diarrhea and HUS; C jejuni was isolated from her stool. The 2-year-old daughter had been admitted five days prior to her mother with HUS following a three-day prodrome of vomiting and diarrhea. Multiple stool cultures were negative for enteric pathogens; however, cultures were not obtained until the eighth hospital day and after antibiotic therapy. Extensive investigation failed to identify another cause for the diarrheal illness or HUS in our patients. Indirect immunofluorescent antibody titers for C jejuni were 1:32 and 1:16 for the mother and daughter, respectively. An asymptomatic 9-month-old son had C jejuni isolated from his stool and had an immunofluorescent antibody titer of 1:64. Three other family members were asymptomatic, stool-culture negative, and had immunofluorescent antibody titers less than or equal to 1:4. The susceptibility to develop HUS following an enteric antigenic stimulus is illustrated by the patients presented. The need for systematic investigation of all HUS cases for potential susceptibility markers, as well as an exhaustive etiologic search, is emphasized.

    View details for Web of Science ID A1983QB20500021

    View details for PubMedID 6823430



    We report two patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in whom peritonitis developed and nontuberculous mycobacteria were isolated from peritoneal fluid. In one, Mycobacterium avium-intracellularis was the only organism isolated. Despite a three-month course of antibiotics to which the organism showed in vitro sensitivity, there was no apparent response. The patient died, and an autopsy showed disseminated mycobacterial disease. In the second case, Mycobacterium fortuitum and diphtheroids were isolated from the peritoneal fluid. Although it was not clear that the mycobacterium was solely responsible for the peritonitis in the second case, the infection failed to resolve with antibiotic therapy appropriate for diphtheroids. This patient also died. Both patients had indolent, chronic infections, although there was granulocyte predominance in the peritoneal fluid. Both had involvement of the catheter exit site. To our knowledge, these are the first reported cases of nontuberculous mycobacterial peritonitis in CAPD patients. We recommend evaluation for mycobacteria, including cultures and stains of dialysate specimens, in all cases of CAPD-associated peritonitis where no organism is identified, or where no improvement is noted after 48 hours of therapy. Repeated cultures for mycobacteria are appropriate for suggestive cases. Since these infections are difficult to treat, it may be prudent to remove the dialysis catheter if they are isolated.

    View details for Web of Science ID A1983QQ40800005

    View details for PubMedID 6846333



    The importance of surgical contributions to successful pediatric continuous ambulatory peritoneal dialysis demonstrated in this review of our experience with 9 pediatric patients maintained on such dialysis for 2 to 21 months (mean 11.3 months). Specific surgical procedures for pediatric peritoneal catheter placement have been developed that ensure proper catheter position, establish a watertight seal at the peritoneum and provide for intraoperative demonstration of good catheter function. Peritoneography at the time of catheter placement had predicted accurately later clinical hernia development and may be used to repair prophylactically subclinical inguinal and umbilical defects that are only demonstrable by intraoperative peritoneography. Partial omentectomy also has been helpful in certain instances. Since institution of the techniques described in this report, our 9 young patients have accumulated 101 patient-months on continuous ambulatory peritoneal dialysis without a single catheter failure. The benefits of this as yet unrestricted extension of peritoneal catheter functional life span may be attributed to the catheter-protective features of the continuous ambulatory peritoneal dialysis method itself and the involvement of interested surgeons as active members of the pediatric continuous ambulatory peritoneal dialysis program.

    View details for Web of Science ID A1982NQ71600027

    View details for PubMedID 7062425



    We report 3 cases of cystine calculi. The stones were dissolved by pelviocaliceal irrigation with tromethamine-E, performed either through a percutaneous nephrostomy tube or ureteral catheters. The 25, 27 and 37-day courses of irrigation were well tolerated by all patients. Complications included a single asymptomatic urinary tract infection that required antibiotic therapy and transient hematuria due to catheter irritation. Our experience demonstrates that cystine calculi, including staghorn, can be dissolved by tromethamine-E irrigation, thereby obviating the need for surgical intervention.

    View details for Web of Science ID A1982QA15900035

    View details for PubMedID 7154186

  • POLYURIC MEGALOCYSTIS JOURNAL OF UROLOGY TANK, E. S., Alexander, S. R., Craven, R. M. 1980; 124 (5): 692-694


    We diagnosed and treated 5 children with huge bladders and hydroureteronephrosis secondary to polyuria, resulting from either familial nephrogenic diabetes insipidus, medullary cystic disease, central diabetes insipidus secondary to panhypopituitarism or psychogenic polydipsia. Polyuria was documented by the measurement of 24-hour urine volumes. The possibility of anatomic and physiologic outlet obstruction was eliminated by flowmetry, voiding cystourethrography and endoscopy.

    View details for Web of Science ID A1980KS68700034

    View details for PubMedID 6450288



    The conversion of exogenous arachidonic acid into prostaglandins was studied in human placenta and fetal membrane microsomes. Only one prostaglandin was formed, prostaglandin E2 (PGE2), in fetal membrane microsomes. In placental microsomes PGE2 was further transformed into 15 keto-PGE2. Cofactor requirements and some characteristics of the system were studied. 1 to 3% conversion of arachidonic acid into prostaglandins was observed in placental microsomes and 5 to 8% conversion in fetal membrane microsomes.

    View details for Web of Science ID A1978EL87500003

    View details for PubMedID 24235

  • ALLERGIC COUGH SYNDROME SOUTHERN MEDICAL JOURNAL Murray, J. A., ALEXANDE, S. R., TRAVIS, B. T., McGovern, J. P. 1970; 63 (10): 1159-?

    View details for Web of Science ID A1970H381600014

    View details for PubMedID 5485587