Cynthia Wong

All Publications

• The Preserving Kidney Function in Children With CKD (PRESERVE) Study: Rationale, Design, and Methods. Kidney medicine Denburg, M. R., Razzaghi, H., Goodwin Davies, A. J., Dharnidharka, V., Dixon, B. P., Flynn, J. T., Glenn, D., Gluck, C. A., Harshman, L., Jovanovska, A., Katsoufis, C. P., Kratchman, A. L., Levondosky, M., Levondosky, R., McDonald, J., Mitsnefes, M., Modi, Z. J., Musante, J., Neu, A. M., Pan, C. G., Patel, H. P., Patterson, L. T., Schuchard, J., Verghese, P. S., Wilson, A. C., Wong, C., Forrest, C. B. 2023; 5 (11): 100722

  Abstract

  Rationale & Objective: PRESERVE seeks to provide new knowledge to inform shared decision-making regarding blood pressure (BP) management for pediatric chronic kidney disease (CKD). PRESERVE will compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; expand the National Patient-Centered Clinical Research Network (PCORnet) common data model by adding pediatric- and kidney-specific variables and linking electronic health record data to other kidney disease databases; and assess the lived experiences of patients related to BP management.Study Design: Multicenter retrospective cohort study (clinical outcomes) and cross-sectional study (patient-reported outcomes [PROs]).Setting & Participants: PRESERVE will include approximately 20,000 children between January 2009-December 2022 with mild-moderate CKDfrom 15 health care institutions that participate in6 PCORnet Clinical Research Networks (PEDSnet, STAR, GPC, PaTH, CAPRiCORN, and OneFlorida+). The inclusion criteria were≥1 nephrologist visit and≥2 estimated glomerular filtration rate (eGFR) values in the range of 30 to<90mL/min/1.73m2 separated by≥90 days without an intervening value≥90mL/min/1.73m2 and no prior dialysis or kidney transplant.Exposures: BP measurements (clinic-based and 24-hour ambulatory BP); urine protein; and antihypertensive treatment by therapeutic class.Outcomes: The primary outcome is a composite event of a 50% reduction in eGFR, eGFR of<15mL/min/1.73m2, long-term dialysis or kidney transplant. Secondary outcomes include change in eGFR, adverse events, and PROs.Analytical Approach: Longitudinal models for dichotomous (proportional hazards or accelerated failure time) and continuous (generalized linear mixed models) clinical outcomes; multivariable linear regression for PROs. We will evaluate heterogeneity of treatment effect by CKD etiology and degree of proteinuria and will examine variation in hypertension management and outcomes based on socio-demographics.Limitations: Causal inference limited by observational analyses.Conclusions: PRESERVE will leverage the PCORnet infrastructure to conduct large-scale observational studies that address BP management knowledge gaps for pediatric CKD, focusing on outcomes that are meaningful to patients.Plain-Language Summary: Hypertension is a major modifiable contributor to loss of kidney function in chronic kidney disease (CKD). The purpose of PRESERVE is to provide evidence to inform shared decision-making regarding blood pressure management for children with CKD. PRESERVE is a consortium of 16 health care institutions in PCORnet, the National Patient-Centered Clinical Research Network, and includes electronic health record data for>19,000 children with CKD. PRESERVE will (1) expand the PCORnet infrastructure for research in pediatric CKD by adding kidney-specific variables and linking electronic health record data to other kidney disease databases; (2) compare the effectiveness of alternative strategies for monitoring and treating hypertension on preserving kidney function; and (3) assess the lived experiences of patients and caregivers related to blood pressure management.

  View details for DOI 10.1016/j.xkme.2023.100722

  View details for PubMedID 37965485

• Immunosuppression and recurrence free parental donor kidney transplant in patient with previous graft loss secondary to recurrent FSGS using prospective a/b T cell, CD19 depleted haploidentical parental stem cell transplant Grimm, P., Wong, C., Goldstein-Fuchs, D., Chaudhuri, A., James, G., Boyd, D., Good, J., Woo, M., Gallo, A., Bertaina, A. SPRINGER. 2023: 2332

  View details for Web of Science ID 001000390500210

• Illness-related parental stress and quality of life in children with kidney diseases. Pediatric nephrology (Berlin, Germany) Patel, R., Wong, C. 2023

  View details for DOI 10.1007/s00467-023-06041-6

  View details for PubMedID 37330454

• Utilising low-cost, easy-to-use microscopy techniques for early peritonitis infection screening in peritoneal dialysis patients. Scientific reports Buckup, M., Kaneda, J. M., Birk, A. M., Glockner, E., Venook, R., Jain, A., Sharma, S., Wong, C., Sutha, K. 2022; 12 (1): 14046

  Abstract

  Peritoneal dialysis (PD) patients are at high risk for peritonitis, an infection of the peritoneum that affects 13% of PD users annually. Relying on subjective peritonitis symptoms results in delayed treatment, leading to high hospitalisation costs, peritoneal scarring, and premature transition to haemodialysis. We have developed and tested a low-cost, easy-to-use technology that uses microscopy and image analysis to screen for peritonitis across the effluent drain tube. Compared to other technologies, our prototype is made from off-the-shelf, low-cost materials. It can be set up quickly and key stakeholders believe it can improve the overall PD experience. We demonstrate that our prototype classifies infection-indicating and healthy white blood cell levels in clinically collected patient effluent with 94% accuracy. Integration of our technology into PD setups as a screening tool for peritonitis would enable earlier physician notification, allowing for prompt diagnosis and treatment to prevent hospitalisations, reduce scarring, and increase PD longevity. Our findings demonstrate the versatility of microscopy and image analysis for infection screening and are a proof of principle for their future applications in health care.

  View details for DOI 10.1038/s41598-022-18380-9

  View details for PubMedID 35982214

• Kidney Replacement Therapy in Low Birth Weight Preterm Newborns. Pediatrics Sutherland, S. M., Davis, A. S., Powell, D., Tanaka, J., Woo, M., Josephs, S., Wong, C. J. 2022

  Abstract

  Managing newborns with kidney failure is a complex undertaking; even under ideal circumstances, dialysis is technically challenging and available therapies are designed for adults. These issues are exacerbated in smaller newborns, and intervention has traditionally not been offered in those below a certain weight threshold. Ethical concerns abound and patients deemed too small for dialysis are typically transitioned to comfort or palliative care. However, many of these neonates are otherwise healthy and would be considered survivable if kidney replacement therapy were available. To challenge the existing paradigm, we present 7 preterm, low birth weight neonates with end-stage kidney disease who were successfully managed using an innovative approach to kidney replacement therapy. These newborns had a median gestational age of 32 weeks (interquartile range [IQR], 32-35) and a median birth weight of 1.58 kg (IQR, 1.41-2.01). Kidney replacement therapy was initiated at a median age of 16 days (IQR, 1.5-40) and a weight of 1.85 kg (IQR, 1.57-2.1). Five of the 7 newborns (71%) survived to hospital discharge. Kidney replacement therapy was provided using 3F and 4F single lumen catheters and a modified ultrafiltration device. Patients experienced excellent metabolic control, and fluid homeostasis was achieved in the first week of life. Furthermore, survivors experienced physiologic weight gain and linear growth throughout their hospitalization. These findings, although preliminary, are encouraging for our smallest patients with kidney failure and suggest that survivability thresholds should be reexamined. At a minimum, neonatologists should be aware that novel approaches exist and may be considered for these challenging patients.

  View details for DOI 10.1542/peds.2022-056570

  View details for PubMedID 35945293

• Low variability of plant protein intake in the CKiD cohort does not demonstrate changes in estimated GFR nor electrolyte balance. Pediatric nephrology (Berlin, Germany) Shah, L. N., Matheson, M. B., Furth, S. L., Schwartz, G. J., Warady, B. A., Wong, C. J. 2021

  Abstract

  BACKGROUND: Vegetable or plant-based sources of protein may confer health benefits in children with progressive kidney disease. Our aims were to understand the effect of the proportion of vegetable protein intake on changes in estimated GFR and to understand the effect of the proportion of vegetable protein intake on serum levels of bicarbonate, phosphorus, and potassium.METHODS: Children with baseline eGFR between 30 and 90 mL/min/1.73 m2 were recruited from 59 centers across North America as part of the chronic kidney disease in children (CKiD) study. The percentage of dietary vegetable protein (VP%) was gathered from annual Food Frequency Questionnaires. We performed longitudinal linear mixed models to determine the effect of VP% on eGFR and longitudinal logistic mixed models to determine the effect of VP% on electrolyte balance (potassium, phosphorus, bicarbonate).RESULTS: Two thousand visits from 631 subjects. Across all dichotomized groups of children (sex, African American race, Hispanic ethnicity, glomerular etiology of CKD, hypertension, anemia, hyperkalemia, hyperphosphatemia, acidosis, BMI < 95th percentile), the median VP% was 32-35%. The longitudinal mixed model analysis did not show any effect of VP% on eGFR electrolyte (bicarbonate, phosphorus, and potassium) abnormalities (p > 0.1).CONCLUSIONS: A diverse cohort of children with CKD has a narrow and homogeneous intake of vegetable protein. Due to the low variability of plant-based protein in the cohort, there were no associations between the percentage of plant protein intake and changes in eGFR nor electrolyte balance. A higher resolution version of the Graphical abstract is available as Supplementary information.

  View details for DOI 10.1007/s00467-021-05334-y

  View details for PubMedID 34796391

• Peri-transplant aminophylline in pediatric kidney transplant recipients of donation after brain death: a double-blinded placebo-controlled randomized clinical trial. Pediatric nephrology (Berlin, Germany) Haskin, O., Shih, W., Wong, C. J., Axelrod, D. M., Grimm, P. C. 2020

  Abstract

  BACKGROUND: During kidney transplantation, the transplanted kidney undergoes ischemia reperfusion injury, with adenosine being a major mediator. This study aimed to assess whether aminophylline, an adenosine receptor antagonist, improves early graft function and reduces incidence of delayed graft function (DGF) and slow graft function (SGF).METHODS: Single center, double-blinded, placebo-controlled randomized clinical trial. Pediatric patients admitted for renal transplantation from donation after brain death donors were randomized into a treatment arm receiving aminophylline and a placebo arm receiving normal saline infusions. Primary outcome was estimated glomerular filtration rate (eGFR) at 5days post-transplant. Secondary outcomes were rates of DGF/SGF and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels.RESULTS: Twenty-three patients were randomized to aminophylline and 27 to placebo. There was no difference in day 5 eGFR, rate of DGF/SGF, or urine NGAL/Creatinine level between aminophylline vs. placebo arm (eGFR 67.39±38.9ml/min/1.73m2 vs. 80.48±52.1ml/min/1.73m2p=0.32; DGF/SGF 5/23 (21.7%) vs. 3/27 (11.1%) p=0.31; urine NGAL/creatinine 300.5ng/mg IQR 105.5-1464.5ng/mg vs. 425.4ng/mg IQR 140.3-1126.2ng/mg, p=0.95; respectively). At 12months, there was 100% patient survival and 98% graft survival. eGFR at 12months was similar between the two arms.CONCLUSIONS: There was no benefit in peri-transplant aminophylline administration. Our results are limited by small sample size, since sample calculations were based on primary outcome of day 5 eGFR and low rate of DGF/SGF, which may have precluded us from demonstrating efficacy. Further clinical studies are necessary to determine any benefit of aminophylline in kidney transplant recipients, particularly from high-risk donors.

  View details for DOI 10.1007/s00467-020-04561-z

  View details for PubMedID 32418145

• Maintenance Peritoneal Dialysis in Children With Autosomal Recessive Polycystic Kidney Disease: A Comparative Cohort Study of the International Pediatric Peritoneal Dialysis Network Registry. American journal of kidney diseases : the official journal of the National Kidney Foundation Akarkach, A. n., Burgmaier, K. n., Sander, A. n., Hooman, N. n., Sever, L. n., Cano, F. n., Zambrano, P. n., Bilge, I. n., Flynn, J. T., Yavascan, O. n., Vallés, P. G., Munarriz, R. L., Patel, H. P., Serdaroglu, E. n., Koch, V. H., Suarez, A. D., Galanti, M. n., Celedon, C. G., Rébori, A. n., Kari, J. A., Wong, C. J., Elenberg, E. n., Rojas, L. F., Warady, B. A., Liebau, M. C., Schaefer, F. n. 2020

  View details for DOI 10.1053/j.ajkd.2019.10.009

  View details for PubMedID 31983502

• 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

  Abstract

  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

• Global Variation of Nutritional Status in Children Undergoing Chronic Peritoneal Dialysis: A Longitudinal Study of the International Pediatric Peritoneal Dialysis Network. Scientific reports Schaefer, F., Benner, L., Borzych-Duzalka, D., Zaritsky, J., Xu, H., Rees, L., Antonio, Z. L., Serdaroglu, E., Hooman, N., Patel, H., Sever, L., Vondrak, K., Flynn, J., Rebori, A., Wong, W., Holtta, T., Yildirim, Z. Y., Ranchin, B., Grenda, R., Testa, S., Drozdz, D., Szabo, A. J., Eid, L., Basu, B., Vitkevic, R., Wong, C., Pottoore, S. J., Muller, D., Dusunsel, R., Celedon, C. G., Fila, M., Sartz, L., Sander, A., Warady, B. A., International Pediatric Peritoneal Dialysis Network (IPPN) Registry, Adragna, M., Coccia, P. A., Suarez, A., Valles, P. G., Salim, R., Alconcher, L., Arbeiter, K., van Hoeck, K., Koch, V., Feber, J., Harvey, E., White, C., Valenzuela, M., Villagra, J., Cano, F., Contreras, M. A., Vogel, A., Zambrano, P., Hevia, P., Chiu, M. C., Ding, J., Vanegas, J. J., Higuita, L. M., Roussey, G., Ulinski, T., Krid, S., Fischbach, M., Harambat, J., Samaille, C., Buscher, R., Oh, J., Pape, L., John, U., Klaus, G., Billing, H., Stafanidis, C., Papachristou, F., Bagga, A., Kanitkar, M., Sinha, R., Sethi, S., Verrina, E., Vidal, E., Leozappa, G., Landau, D., Ha, I. S., Paik, K. H., Bilal, A., Sahpazova, E., Lim, Y. N., Barbosa, L. S., Groothoff, J. W., Konijenberg, Y., Silva, Y., Ryami, M. A., Munarriz, R. L., Leszczynska, B., Szczepanska, M., Brumariu, O., Kari, J., Kruscic, D., Yap, H. K., Ariceta, G., Aguirre, M., Santos, F., Niwinska-Faryna, B., Bayazit, A., Bakkaloglu, C. A., Bakkaloglu, S., Bilge, I., Yavascan, O., Mir, S., Simkova, E., Christian, M., Greenbaum, L., Neu, A., Askenazi, D., Al-Akash, A., Swartz, S., Brophy, P., Rheault, M., Pradhan, M. 2019; 9 (1): 4886

  Abstract

  While children approaching end-stage kidney disease (ESKD) are considered at risk of uremic anorexia and underweight they are also exposed to the global obesity epidemic. We sought to investigate the variation of nutritional status in children undergoing chronic peritoneal dialysis (CPD) around the globe. The distribution and course of body mass index (BMI) standard deviation score over time was examined prospectively in 1001 children and adolescents from 35 countries starting CPD who were followed in the International Pediatric PD Network (IPPN) Registry. The overall prevalence of underweight, and overweight/obesity at start of CPD was 8.9% and 19.7%, respectively. Underweight was most prevalent in South and Southeast Asia (20%), Central Europe (16.7%) and Turkey (15.2%), whereas overweight and obesity were most common in the Middle East (40%) and the US (33%). BMI SDS at PD initiation was associated positively with current eGFR and gastrostomy feeding prior to PD start. Over the course of PD BMI SDS tended to increase on CPD in underweight and normal weight children, whereas it decreased in initially overweight patients. In infancy, mortality risk was amplified by obesity, whereas in older children mortality was markedly increased in association with underweight. Both underweight and overweight are prevalent in pediatric ESKD, with the prevalence varying across the globe. Late dialysis start is associated with underweight, while enteral feeding can lead to obesity. Nutritional abnormalities tend to attenuate with time on dialysis. Mortality risk appears increased with obesity in infants and with underweight in older children.

  View details for DOI 10.1038/s41598-018-36975-z

  View details for PubMedID 30894599

• Priapism and hemodialysis: Case report and literature review CLINICAL NEPHROLOGY Shih, W., Wong, C. 2018; 90 (1): 64–70

  Abstract

  Priapism is a known but rarely described complication of patients on dialysis. The incidence of priapism in the general population is estimated at 1.5 in 100,000 patients and 2.9 in 100,000 patients in males over 40 years of age; however there is little current literature describing priapism in adult dialysis patients and no current literature in pediatric dialysis patients [1]. We describe two pediatric patients who developed priapism concurrent with hemodialysis, each with differing severity and therapeutic management. Case diagnosis/treatment: Two adolescent males presented with painful erection during a chronic hemodialysis treatment. Patient 1 required urologic intervention for management and treatment. Further medical treatment subsequently led to pseudoephedrine intoxication which self-resolved. Patient 2's priapism course self-resolved with adjustment in hemoglobin targets and did not require further surgical or medical intervention. Neither had recurrent episodes of priapism with careful management to maintain hemoglobin levels between 11 and 12 g/dL.Priapism is a rarely reported complication of dialysis in adult patients and has not been described in pediatric dialysis patients. The etiology remains unclear but is hypothesized to be multifactorial including heparin-associated effects and epoetin administration. In our patients, commonality between the two included presumed high androgen levels (given age) and borderline to high hemoglobin levels in patients receiving epoetin alfa. This in combination with prior studies highlights the possible role epoetin administration may play. The role of heparin remains a possibility but is unclear. Further studies are needed to more clearly elucidate the etiology..

  View details for DOI 10.5414/CN109416

  View details for Web of Science ID 000435373000011

  View details for PubMedID 29578404

• Epidemiology of peritonitis following maintenance peritoneal dialysis catheter placement during infancy: a report of the SCOPE collaborative PEDIATRIC NEPHROLOGY Zaritsky, J., Hanevold, C., Quigley, R., Richardson, T., Wong, C., Ehrlich, J., Lawlor, J., Rodean, J., Neu, A., Warady, B. A., SCOPE Investigators 2018; 33 (4): 713–22

  Abstract

  Maintenance peritoneal dialysis (PD) is the dialysis modality of choice for infants and young children. However, there are limited outcome data for those who undergo PD catheter insertion and initiate maintenance PD within the first year of life.Using data from the Children's Hospital Association's Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (ESRD) Collaborative (SCOPE), we examined peritonitis rates and patient survival in 156 infants from 29 North American pediatric dialysis centers who had a chronic PD catheter placed prior to their first birthday.In-hospital and overall annualized rates of peritonitis were 1.73 and 0.76 episodes per patient-year, respectively. Polycystic kidney disease was the most frequent renal diagnosis and pulmonary hypoplasia the most common co-morbidity in infants with peritonitis. Multivariable regression models demonstrated that nephrectomy at or prior to PD catheter placement and G-tube insertion after catheter placement were associated with a nearly sixfold and nearly threefold increased risk of peritonitis, respectively. Infants with peritonitis had longer initial hospital stays and lower overall survival (86.3 vs. 95.6%, respectively; P < 0.02) than those without an episode of peritonitis.In this large cohort of infants with ESRD, the frequency of peritonitis was high and several risk factors associated with the development of peritonitis were identified. Given that peritonitis was associated with a longer duration of initial hospitalization and increased mortality, increased attention to the potentially modifiable risk factors for infection is needed.

  View details for DOI 10.1007/s00467-017-3839-5

  View details for Web of Science ID 000427901900019

  View details for PubMedID 29150711

• CHILDREN TOLERATE INTRADIALYTIC ORAL NUTRITION JOURNAL OF RENAL CARE South, A. M., Fainman, B., Sutherland, S. M., Wong, C. J. 2018; 44 (1): 38–43

  Abstract

  People undergoing haemodialysis (HD) often have poor nutrition, which in turn can contribute to worse outcomes. Inadequate nutrition has a particularly deleterious effect on growth and neurocognitive development, as well as mortality, in children and adolescents. Nutritional supplementation can improve outcomes but can be difficult to administer.Determine the tolerability of intradialytic oral nutrition in children and adolescents.A cross-sectional quality improvement study in an outpatient paediatric HD unit. Intervention was intradialytic oral nutritional supplementation provided as protein bars and/or meals.Children and adolescents undergoing outpatient HD who were able to participate in surveys and eat by mouth.Adverse effects and symptoms on nurse- and patient-reported surveys, respectively. Relationships between the predictor variables and the outcomes were assessed using generalised estimating equations.The majority of children felt better after eating on dialysis (72%) with no adverse effects (80%). On unadjusted analyses and confirmed with generalised estimating equation modelling, children who reported being hungry felt better after eating on dialysis, despite being more likely to have adverse effects.The study demonstrates that our children and adolescents feel better after eating on HD with minimal adverse effects. The finding that hungry patients are more likely to feel better despite having a higher likelihood of an adverse effect demonstrates the tolerability of eating on HD. Intradialytic oral nutrition could be a safe and well-tolerated opportunity to provide supplemental nutrition to paediatric HD patients and improve outcomes.

  View details for PubMedID 29230952

• De novo weekly and biweekly darbepoetin alfa dosing in pediatric patients with chronic kidney disease PEDIATRIC NEPHROLOGY Warady, B. A., Barcia, J., Benador, N., Jankauskiene, A., Olson, K., Podracka, L., Shavkin, A., Srivaths, P., Wong, C. J., Petersen, J. 2018; 33 (1): 125–37

  Abstract

  Darbepoetin alfa is a commonly prescribed erythropoiesis-stimulating agent (ESA) for correcting anemia in pediatric chronic kidney disease (CKD) patients. However, little information exists on its use in ESA-naïve patients. This study evaluated the efficacy and safety of darbepoetin alfa in pediatric patients initiating ESA therapy.One-hundred sixteen pediatric ESA-naïve subjects (aged 1-18 years) with CKD stages 3-5D and hemoglobin (Hb) <10 g/dl from 43 centers in the US, Europe, and Mexico were randomized by age (three groups) and dialysis status (yes vs. no) to receive darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) subcutaneously (not on dialysis and peritoneal dialysis subjects) and intravenously (hemodialysis subjects). The drug was titrated to achieve Hb levels of 10.0-12.0 g/dl over 25 weeks. Patient- and parent-reported health-related outcomes were measured by the Pediatric Quality of Life Inventory (PedsQL™) in children ≥2 years.In both groups, mean Hb concentrations increased to ≥11.0 g/dl over the first 3 months of treatment and remained stable within the 10.0-12.0 g/dl target range. The median time to achieve hemoglobin ≥10 g/dl was slightly longer for subjects <12 years (QW and Q2W, both 28 days) vs. those ≥12 years (23 and 22 days, respectively). Adverse event profiles were similar between groups, with QW, four (7%) and Q2W, five (9%). PedsQL™ scores showed modest increases.Darbepoetin alfa can be safely administered either QW or Q2W to ESA-naïve pediatric patients with CKD-related anemia to achieve Hb targets of 10.0-12.0 g/dl.

  View details for PubMedID 28815341

• The Effect of Intradialytic Intralipid Therapy in Pediatric Hemodialysis Patients. Journal of renal nutrition Haskin, O., Sutherland, S. M., Wong, C. J. 2017; 27 (2): 132-137

  Abstract

  Growth of children on maintenance hemodialysis is poor. Oral nutritional supplements are the preferred way to augment nutrition; however, many children have difficulties adhering to prescribed oral supplements. In our unit, we have been utilizing intralipid (IL) therapy as nutritional supplement during hemodialysis sessions. The aim of this study was to assess the safety, efficacy, and benefits of intradialytic IL therapy.A retrospective chart review.Fifteen pediatric hemodialysis patients receiving intradialytic IL therapy for at least 3 months from July 2011 through July 2014.For each patient, anthropometric measurements and laboratory nutritional parameters were compared prior to and at the end of IL therapy. Anthropometric measurements evaluated were dry weight, height, body mass index (BMI), and BMI corrected for height age. Laboratory nutritional parameters evaluated were albumin, normalized protein catabolic rate, predialysis blood urea nitrogen, transferrin, cholesterol, and triglyceride levels. Adverse events during therapy were also noted.Significant improvement was noted in albumin levels, predialysis blood urea nitrogen, and normalized protein catabolic rate during therapy (P = .02; P = .03; P = .03, respectively). Six patients (37.5%) improved their weight standard deviation score, and eight patients (50%) improved their BMI standard deviation score though not statistically significant (P = .59; P = .9, respectively). No significant side effects were noted.Administration of IL alone during hemodialysis is well tolerated with beneficial effects on nutritional parameters. The provision of IL alone is relatively cheap and does not require additional resources. In conjunction with other measures of nutritional support, it can help improve nutritional status of pediatric hemodialysis patients.

  View details for DOI 10.1053/j.jrn.2016.10.003

  View details for PubMedID 27923526

• Effect of elevated blood pressure on quality of life in children with chronic kidney disease PEDIATRIC NEPHROLOGY Wong, C., Gerson, A., Hooper, S. R., Matheson, M., Lande, M., Kupferman, J., Furth, S., Warady, B., Flynn, J. 2016; 31 (7): 1129-1136

  Abstract

  Although hypertension is known to have an adverse impact on health-related quality of life (HRQoL) in adults, little is known about the effects of hypertension and use of antihypertensive medications on HRQoL in hypertensive children with chronic kidney disease (CKD).Cross-sectional and longitudinal assessment of impact of elevated blood pressure (BP) and antihypertensive medication use on HRQoL scores obtained in children enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Blood pressure was measured both manually and by ambulatory blood pressure monitoring. HRQoL was assessed with the PedsQL survey.The study sample included 551 participants with sufficient data for cross-sectional and longitudinal analyses. Cross-sectional analysis of presence of prehypertension or hypertension and impact on HRQoL found mild associations between elevated BP and HRQoL scores with overall PedsQL parent and child scores averaging 79 vs. 76.5 and 83 vs. 78.5, respectively. However, no associations persisted under longitudinal multivariate analysis.Despite apparent small effects of elevated BP on HRQoL at baseline, no association was found between the presence of elevated BP and HRQoL over time in children with mild-to-moderate CKD. In addition, antihypertensive medication use did not appear to have an impact on HRQoL in this population.

  View details for DOI 10.1007/s00467-015-3262-8

  View details for Web of Science ID 000376925900013

  View details for PubMedID 26857712

• 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

  Abstract

  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

• 44-h ambulatory blood pressure monitoring: revealing the true burden of hypertension in pediatric hemodialysis patients. Pediatric nephrology Haskin, O., Wong, C. J., McCabe, L., Begin, B., Sutherland, S. M., Chaudhuri, A. 2015; 30 (4): 653-660

  Abstract

  The blood pressure (BP) burden is high in pediatric hemodialysis (HD) patients and adversely affects prognosis. The aim of this study was to examine whether 44-h ambulatory BP monitoring (ABPM) provides additional relevant BP data compared with 24-h ABPM.ABPM was initiated at the end of the mid-week dialysis run in 13 stable pediatric HD patients and continued until the next run for 44 h. Day 1 was defined as the initial 24-h ABPM and Day 2 as the time period after that until the next dialysis run. All patients had an echocardiogram to calculate the left ventricular mass index (LVMI).A higher percentage of patients were diagnosed with hypertension from the 44-h ABPM than from the 24-h ABPM. All BP indexes and loads (except nighttime diastolic load) were significantly higher on Day 2 than on Day 1. Patients with BP loads of ≥25 % on 44-h ABPM had significantly higher LVMI than those patients with normal BP loads. No such association was found with 24-h ABPM and LVMI. Higher interdialytic weight gain was associated with higher Day-2 nighttime systolic BP load.The 44-h ABPM provides more information than the 24-h ABPM in terms of diagnosing and assessing the true burden of hypertension in pediatric HD patients. Elevated BP loads from 44-h ABPM correlate with a higher LVMI on the echocardiogram.

  View details for DOI 10.1007/s00467-014-2964-7

  View details for PubMedID 25266709

• Whole-body single-frequency bioimpedance analysis in pediatric hemodialysis patients PEDIATRIC NEPHROLOGY Oh, G., Wong, C., Begin, B., Salsbery, K., Sutherland, S., Chaudhuri, A. 2014; 29 (8): 1417-1423

  Abstract

  We hypothesized that the percent change in resistance (%RΔ) from bioimpedance analysis (BIA) measurements during hemodialysis (HD) can provide information on pediatric HD patients' hydration status.Whole-body single-frequency BIA measurements were obtained before HD, each hour on HD, and after HD during two HD sessions. Pre-and post-HD weights, blood pressures, Crit-Line® measurements, and intradialytic symptoms were collected on the day of the BIA measurements.One hundred and thirty BIA measurements were obtained from 14 HD patients. The group was 43 % girls, and the mean age was 13.2 ± 4.4 years. Percent change in resistance was 13.5 ± 10.8 % at the end of HD; %RΔ correlated with percent body weight change (%BWΔ) following HD (r = -0.83, P < 0.01), as well as with percent blood volume change (%BVΔ) (r = -0.79, P < 0.01). The %RΔ was similar between patients with and without hypertension immediately before HD and was greater in those with intradialytic symptoms (19.1 ± 7.7 %) than in those without (9.9 ± 11.2 %) (P = 0.02). Patients with left ventricular hypertrophy (LVH) had lower %RΔ (7.2 ± 9.7 %) than those without (19.5 ± 7.7 %) (P = 0.03). Left ventricular mass index (LVMI) also correlated strongly with %RΔ (r = -0.79, P = 0.004) and %BWΔ (r = 0.82, P = 0.002).Our study showed that %RΔ strongly correlates with %BWΔ and %BVΔ and that %RΔ also correlated with intradialytic symptoms and LVMI.

  View details for DOI 10.1007/s00467-014-2778-7

  View details for Web of Science ID 000338700400017

• Whole-body single-frequency bioimpedance analysis in pediatric hemodialysis patients. Pediatric nephrology (Berlin, Germany) Oh, G., Wong, C., Begin, B., Salsbery, K., Sutherland, S., Chaudhuri, A. 2014

  Abstract

  We hypothesized that the percent change in resistance (%RΔ) from bioimpedance analysis (BIA) measurements during hemodialysis (HD) can provide information on pediatric HD patients' hydration status.Whole-body single-frequency BIA measurements were obtained before HD, each hour on HD, and after HD during two HD sessions. Pre-and post-HD weights, blood pressures, Crit-Line® measurements, and intradialytic symptoms were collected on the day of the BIA measurements.One hundred and thirty BIA measurements were obtained from 14 HD patients. The group was 43 % girls, and the mean age was 13.2 ± 4.4 years. Percent change in resistance was 13.5 ± 10.8 % at the end of HD; %RΔ correlated with percent body weight change (%BWΔ) following HD (r = -0.83, P < 0.01), as well as with percent blood volume change (%BVΔ) (r = -0.79, P < 0.01). The %RΔ was similar between patients with and without hypertension immediately before HD and was greater in those with intradialytic symptoms (19.1 ± 7.7 %) than in those without (9.9 ± 11.2 %) (P = 0.02). Patients with left ventricular hypertrophy (LVH) had lower %RΔ (7.2 ± 9.7 %) than those without (19.5 ± 7.7 %) (P = 0.03). Left ventricular mass index (LVMI) also correlated strongly with %RΔ (r = -0.79, P = 0.004) and %BWΔ (r = 0.82, P = 0.002).Our study showed that %RΔ strongly correlates with %BWΔ and %BVΔ and that %RΔ also correlated with intradialytic symptoms and LVMI.

  View details for DOI 10.1007/s00467-014-2778-7

  View details for PubMedID 24570069

• CKiD (CKD in Children) Prospective Cohort Study: A Review of Current Findings AMERICAN JOURNAL OF KIDNEY DISEASES Wong, C. J., Moxey-Mims, M., Jerry-Fluker, J., Warady, B. A., Furth, S. L. 2012; 60 (6): 1002-1011

  Abstract

  Chronic kidney disease (CKD) is a life-long condition associated with substantial morbidity and premature death due to complications from a progressive decrease in kidney function. The incidence and prevalence of all stages of CKD in children continues to increase worldwide. Between 2000 and 2008, the kidney replacement therapy incidence rate in those aged 0-19 years increased 5.9% to 15 per million population, highlighting the importance of CKD research in children. Many comorbid conditions seen in adults with CKD, including cardiovascular disease and cognitive impairment, also are highly prevalent in children, implicitly demonstrating the crucial need for initiating therapy early to improve health outcomes in children with CKD. The CKiD (Chronic Kidney Disease in Children) Study is a prospective cohort study of 586 children aged 1-16 years with an estimated glomerular filtration rate of 30-90 mL/min/1.73 m(2). Since its inception, CKiD has identified risk factors for CKD progression and cardiovascular disease in children with CKD and highlighted the effects of CKD on outcomes unique to children, including neurocognitive development and growth. This review summarizes the findings to date, illustrating the spectrum of CKD-associated complications in children and emphasizing areas requiring further investigation. Taken in sum, these elements stress that initiating treatment at an early age is essential for reducing long-term morbidity and mortality in children with CKD.

  View details for DOI 10.1053/j.ajkd.2012.07.018

  View details for Web of Science ID 000310845100018

  View details for PubMedID 23022429

  View details for PubMedCentralID PMC3496011

• 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

  Abstract

  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

• Casual Blood Pressure and Neurocognitive Function in Children with Chronic Kidney Disease: A Report of the Children with Chronic Kidney Disease Cohort Study CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Lande, M. B., Gerson, A. C., Hooper, S. R., Cox, C., Matheson, M., Mendley, S. R., Gipson, D. S., Wong, C., Warady, B. A., Furth, S. L., Flynn, J. T. 2011; 6 (8): 1831-1837

  Abstract

  Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP.This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project.Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90(th) percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95(th) percentile BP) correlated inversely with Performance IQ score (systolic, r = -0.13, P = 0.01; diastolic, r = -0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = -3.7, 95% confidence interval [CI]: -7.3 to -0.06; systolic BP index, β = -1.16 to 95% CI: -2.1, -0.21; diastolic BP index, β = -1.17, 95% CI: -1.8 to -0.55).Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.

  View details for DOI 10.2215/CJN.00810111

  View details for Web of Science ID 000293721400007

  View details for PubMedID 21700829

  View details for PubMedCentralID PMC3156422

• Donor-specific antibody against denatured HLA-A1: Clinically nonsignificant? HUMAN IMMUNOLOGY Pereira, S., Perkins, S., Lee, J., Shumway, W., LeFor, W., Lopez-Cepero, M., Wong, C., Connolly, A., Tan, J. C., Grumet, F. C. 2011; 72 (6): 492-498

  Abstract

  Pre-transplant screening of a woman with end-stage renal disease (ESRD) showed no anti-human leukocyte antigen (HLA) alloantibodies by anti-human globulin-complement-dependent cytotoxicity (AHG-CDC; class I) or enzyme-linked immunosorbent assay (class II). Following a negative AHG-CDC crossmatch, an HLA*01:01+ deceased donor (DD) kidney was transplanted in September 2005. Subsequent screening of pre-transplant serum by LABScreen Single Antigen (SA) array showed strong reactivity versus A*01:01. Despite that reactivity, at 5 years post-transplant, the patient has a serum creatinine of 1.6 mg/dl and has never experienced humoral or cellular rejection. Retrospective flow-cytometric crossmatch of pre- and post-transplant sera versus DD cells was negative. Rescreening of multiple pre- and post-transplant sera revealed anti-A1 reactivity persisting from the first through the last samples tested. The patient's anti-A1 was almost two fold more reactive with denatured A*01:01 FlowPRA SA beads after denaturation with acid treatment (pH 2.7) than with untreated beads. Parallel results were observed with pH 2.7 treated versus untreated A1+ T cells in FXM. These data highlight the difficulty in interpreting screening results obtained using bead arrays, because of antibodies that appear to recognize denatured but not native class I HLA antigens. We suggest that such bead-positive, flow cytometric crossmatch negative antibodies are not associated with humoral rejection, may not necessarily be detrimental to a graft, and deserve further evaluation before becoming a barrier to transplantation.

  View details for DOI 10.1016/j.humimm.2011.02.012

  View details for Web of Science ID 000291138900005

  View details for PubMedID 21396421

• 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

  Abstract

  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

• 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

  Abstract

  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

• 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

  Abstract

  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

• Severe cryptosporidiosis in a seven-year-old renal transplant recipient - Case report and review of the literature PEDIATRIC TRANSPLANTATION Hong, D. K., Wong, C. J., Gutierrez, K. 2007; 11 (1): 94-100

  Abstract

  Cryptosporidium is an intracellular protozoa that can cause gastroenteritis in humans. In immunocompromised hosts, infection can be severe, leading to life-threatening persistent diarrhea. There is limited experience in treating this infection in solid organ transplants. Although newer drugs active against Cryptosporidium exist, they are only licensed in the USA for treatment of immunocompetent hosts. Here we describe a seven-year-old renal transplant recipient with severe cryptosporidiosis. He had a protracted course of diarrhea of up to 2 L/day. He was successfully managed with combination antimicrobial therapy including nitazoxanide, paromomycin, and azithromycin. In conjunction with this regimen, he had a reduction in immunosuppression and complete bowel rest. His stool pattern normalized in four weeks and he has had no recurrence after six months of follow up.

  View details for DOI 10.1111/j.1399-3046.2006.00593.x

  View details for PubMedID 17239130