- Pediatric Nephrology
- Pediatric Dialysis
- Pediatric Renal Transplantation
- Acute Kidney Injury
Clinical Professor, Pediatrics - Nephrology
Clinical Professor, Pediatrics - Systems Medicine
Associate Chair, Departmental Clinical Services, Stanford School of Medicine, Department of Pediatrics (2017 - Present)
Medical Director, Acute Dialysis Therapies, Lucile Packard Children's Hospital, Stanford School of Medicine (2017 - Present)
Medical Director, Apheresis, Lucile Packard Children's Hospital, Stanford School of Medicine (2017 - Present)
Co-director, Cardiorenal Clinic, Lucile Packard Children's Hospital, Stanford School of Medicine (2015 - Present)
Residency: Stanford Health Care at Lucile Packard Children's Hospital (2005) CA
Medical Education: Yale School Of Medicine (2002) CT
Fellowship: Stanford University Pediatric Nephrology Fellowship (2008) CA
Board Certification: American Board of Pediatrics, Pediatrics (2005)
Board Certification: American Board of Pediatrics, Pediatric Nephrology (2010)
BA, Duke University, Chemistry/Economics (1997)
Independent Studies (5)
- Directed Reading in Pediatrics
PEDS 299 (Win, Spr)
- Early Clinical Experience
PEDS 280 (Win, Spr)
- Graduate Research
PEDS 399 (Win, Spr)
- Medical Scholars Research
PEDS 370 (Win, Spr)
- Undergraduate Directed Reading/Research
PEDS 199 (Win, Spr)
- Directed Reading in Pediatrics
Postdoctoral Research Mentor
Leveraging Big Data and Electronic Health Records to Enhance Novel Approaches to Acute Kidney Injury Research and Care.
2017; 44 (1): 68-76
While acute kidney injury (AKI) has been poorly defined historically, a decade of effort has culminated in a standardized, consensus definition. In parallel, electronic health records (EHRs) have been adopted with greater regularity, clinical informatics approaches have been refined, and the field of EHR-enabled care improvement and research has burgeoned. Although both fields have matured in isolation, uniting the 2 has the capacity to redefine AKI-related care and research. This article describes how the application of a consistent AKI definition to the EHR dataset can accurately and rapidly diagnose and identify AKI events. Furthermore, this electronic, automated diagnostic strategy creates the opportunity to develop predictive approaches, optimize AKI alerts, and trace AKI events across institutions, care platforms, and administrative datasets.
View details for DOI 10.1159/000458751
View details for PubMedID 28268210
Recovery From Acute Kidney Injury and CKD Following Heart Transplantation in Children, Adolescents, and Young Adults: A Retrospective Cohort Study.
American journal of kidney diseases
2016; 68 (2): 212-218
Acute kidney injury (AKI) is common in children following surgery for congenital heart disease and has been associated with poor long-term kidney outcomes. Children undergoing heart transplantation may be at increased risk for the development of both AKI and chronic kidney disease (CKD). This study examines AKI rates in children, adolescents, and young adults after heart transplantation and analyzes the relationship between AKI and CKD in this population.Retrospective cohort study.88 young patients who underwent heart transplantation at Lucile Packard Children's Hospital, Stanford, CA, September 1, 2007, to November 30, 2013.The primary independent variable was AKI within the first 7 postoperative days, ascertained according to the KDIGO (Kidney Disease: Improving Global Outcomes) creatinine criteria (increase in serum creatinine ≥ 1.5 times baseline within 7 days).Recovery from AKI at 3 months, ascertained as serum creatinine level < 1.5 times baseline; and development of CKD at 6 and 12 months, ascertained as estimated glomerular filtration rate < 60mL/min/1.73m(2) for more than 3 months.63 (72%) patients developed AKI; 57% had moderate (stage 2 or severe stage 3) disease. Recovery occurred in 39 of 63 (62%), 50% for stage 2 or 3 versus 78% for stage 1 (P=0.04). At 6 and 12 months, 3 of 82 (4%) and 4 of 76 (5%) developed CKD, respectively. At both time points, CKD was more common in those without recovery (3/22 [14%] vs 0/38 (0%); P=0.04, and 3/17 (18%) vs (0/34) 0%; P=0.03, respectively).Retrospective design, small sample size, and single-center nature of the study.AKI is common after heart transplantation in children, adolescents, and young adults. Nonrecovery from AKI is more common in patients with more severe AKI and is associated with the development of CKD during the first year.
View details for DOI 10.1053/j.ajkd.2016.01.024
View details for PubMedID 26970941
Impact of ventricular assist device placement on longitudinal renal function in children with end-stage heart failure.
journal of heart and lung transplantation
2016; 35 (4): 449-456
Although ventricular assist devices (VADs) restore hemodynamics in those with heart failure, reversibility of end-organ dysfunction with VAD support is not well characterized. Renal function often improves in adults after VAD placement, but this has not been comprehensively explored in children.Sixty-three children on VAD support were studied. Acute kidney injury (AKI) was defined by Kidney Disease: Improving Global Outcomes criteria. Estimated glomerular filtration rate (eGFR) was determined by the Schwartz method. Generalized linear mixed-effects models compared the pre-VAD and post-VAD eGFR for the cohort and sub-groups with and without pre-VAD renal dysfunction (pre-VAD eGFR < 90 ml/min/1.73 m(2)).The pre-VAD eGFR across the cohort was 84.0 ml/min/1.73 m(2) (interquartile range [IQR] 62.3-122.7), and 55.6% (34 of 63) had pre-VAD renal dysfunction. AKI affected 60.3% (38 of 63), with similar rates in those with and without pre-existing renal dysfunction. Within the cohort, the nadir eGFR occurred 1 day post-operatively (62.9 ml/min/1.73 m(2); IQR, 51.2-88.9 ml/min/1.73 m(2); p < 0.001). By Day 5, however, the eGFR exceeded the baseline (99.0 ml/min/1.73 m(2); IQR, 59.3-146.7 ml/min/1.73 m(2); p = 0.03) and remained significantly higher through the first post-operative week. After adjusting for age, gender, and AKI, the eGFR continued to increase throughout the entire 180-day study period (β = 0.0025; 95% confidence interval, 0.0015-0.0036; p < 0.001). Patients with pre-VAD renal dysfunction experienced the greatest improvement in the eGFR (β = 0.0051 vs β = 0.0013, p < 0.001).Renal dysfunction is prevalent in children with heart failure undergoing VAD placement. Although peri-operative AKI is common, renal function improves substantially in the first post-operative week and for months thereafter. This is particularly pronounced in those with pre-VAD renal impairment, suggesting that VADs may facilitate recovery and maintenance of kidney function in children with advanced heart failure.
View details for DOI 10.1016/j.healun.2015.10.039
View details for PubMedID 26653933
Utilizing electronic health records to predict acute kidney injury risk and outcomes: workgroup statements from the 15(th) ADQI Consensus Conference.
Canadian journal of kidney health and disease
2016; 3: 11-?
The data contained within the electronic health record (EHR) is "big" from the standpoint of volume, velocity, and variety. These circumstances and the pervasive trend towards EHR adoption have sparked interest in applying big data predictive analytic techniques to EHR data. Acute kidney injury (AKI) is a condition well suited to prediction and risk forecasting; not only does the consensus definition for AKI allow temporal anchoring of events, but no treatments exist once AKI develops, underscoring the importance of early identification and prevention. The Acute Dialysis Quality Initiative (ADQI) convened a group of key opinion leaders and stakeholders to consider how best to approach AKI research and care in the "Big Data" era. This manuscript addresses the core elements of AKI risk prediction and outlines potential pathways and processes. We describe AKI prediction targets, feature selection, model development, and data display.
View details for DOI 10.1186/s40697-016-0099-4
View details for PubMedID 26925247
View details for PubMedCentralID PMC4768420
AKI in Hospitalized Children: Comparing the pRIFLE, AKIN, and KDIGO Definitions
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2015; 10 (4): 554-561
Although several standardized definitions for AKI have been developed, no consensus exists regarding which to use in children. This study applied the Pediatric RIFLE (pRIFLE), AKI Network (AKIN), and Kidney Disease Improving Global Outcomes (KDIGO) criteria to an anonymized cohort of hospitalizations extracted from the electronic medical record to compare AKI incidence and outcomes in intensive care unit (ICU) and non-ICU pediatric populations.Observational, electronic medical record-enabled study of 14,795 hospitalizations at the Lucile Packard Children's Hospital between 2006 and 2010. AKI and AKI severity stage were defined by the pRIFLE, AKIN, and KDIGO definitions according to creatinine change criteria; urine output criteria were not used. The incidences of AKI and each AKI stage were calculated for each classification system. All-cause, in-hospital mortality and total hospital length of stay (LOS) were compared at each subsequent AKI stage by Fisher exact and Kolmogorov-Smirnov tests, respectively.AKI incidences across the cohort according to pRIFLE, AKIN, and KDIGO were 51.1%, 37.3%, and 40.3%. Mortality was higher among patients with AKI across all definitions (pRIFLE, 2.3%; AKIN, 2.7%; KDIGO, 2.5%; P<0.001 versus no AKI [0.8%-1.0%]). Within the ICU, pRIFLE, AKIN, and KDIGO demonstrated progressively higher mortality at each AKI severity stage; AKI was not associated with mortality outside the ICU by any definition. Both in and outside the ICU, AKI was associated with significantly higher LOS at each AKI severity stage across all three definitions (P<0.001). Definitions resulted in differences in diagnosis and staging of AKI; staging agreement ranged from 76.7% to 92.5%.Application of the three definitions led to differences in AKI incidence and staging. AKI was associated with greater mortality and LOS in the ICU and greater LOS outside the ICU. All three definitions demonstrated excellent interstage discrimination. While each definition offers advantages, these results underscore the need to adopt a single, universal AKI definition.
View details for DOI 10.2215/CJN.01900214
View details for Web of Science ID 000352463400005
View details for PubMedID 25649155
The Prospective Pediatric Continuous Renal Replacement Therapy (ppCRRT) Registry: a critical appraisal
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
Acute kidney injury in the pediatric cardiac patient
2014; 24 (9): 899-901
In summary, AKI after pediatric congenital cardiac surgery represents an important diagnostic and therapeutic challenge in the modern day intensive care unit. AKI in the immediate postoperative period not only portends a poor short-term outcome, but also may relate to chronic kidney disease and mortality in the long term. Its association with increased morbidity, cost, and mortality demands the attention of clinicians and researchers. Future studies should employ a standard AKI definition and should focus on both the mitigation and prevention of AKI events.
View details for DOI 10.1111/pan.12448
View details for Web of Science ID 000340533400002
View details for PubMedID 25092446
Initial Experience Using Aminophylline to Improve Renal Dysfunction in the Pediatric Cardiovascular ICU
PEDIATRIC CRITICAL CARE MEDICINE
2014; 15 (1): 21-27
To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU.Single-center retrospective cohort study.Pediatric cardiovascular ICU, university-affiliated children's hospital.Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload.Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload.Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (-0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m (+3.66 mL/min/1.73 m/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration.Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.
View details for DOI 10.1097/01.pcc.0000436473.12082.2f
View details for PubMedID 24212284
AKI in Hospitalized Children: Epidemiology and Clinical Associations in a National Cohort.
Clinical journal of the American Society of Nephrology
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
Continuous renal replacement therapy in children
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
Evidence-Based Medicine in the EMR Era
NEW ENGLAND JOURNAL OF MEDICINE
2011; 365 (19): 1758-1759
View details for DOI 10.1056/NEJMp1108726
View details for Web of Science ID 000296762800003
View details for PubMedID 22047518
Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy: The Prospective Pediatric Continuous Renal Replacement Therapy Registry
AMERICAN JOURNAL OF KIDNEY DISEASES
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
Acute kidney injury in hospitalized children: consequences and outcomes.
Pediatric nephrology (Berlin, Germany)
Over the past decade, the nephrology and critical care communities have adopted a consensus approach to diagnosing acute kidney injury (AKI) and, as a result, we have seen transformative changes in our understanding of pediatric AKI epidemiology. The data regarding outcomes among neonates and children who develop AKI have become far more robust and AKI has been clearly linked with an increased need for mechanical ventilation, longer inpatient stays, and higher mortality. Though AKI was historically thought to be self-limited, we now know that renal recovery is far from universal, particularly when AKI is severe; the absence of recovery from AKI also carries longitudinal prognostic implications. AKI survivors, especially those without full recovery, are at risk for chronic renal sequelae including proteinuria, hypertension, and chronic kidney disease. This review comprehensively describes AKI-related outcomes across the entire pediatric age spectrum, using the most rigorous studies to identify the independent effects of AKI events.
View details for PubMedID 30386936
Nephrotoxin exposure and acute kidney injury in critically ill children undergoing congenital cardiac surgery.
Pediatric nephrology (Berlin, Germany)
BACKGROUND: Though acute kidney injury (AKI) is often multifactorial, investigators are now emphasizing the specific contribution of nephrotoxins. This study examines the epidemiology of nephrotoxin exposure and nephrotoxin-associated AKI among children undergoing congenital heart surgery (CHS).METHODS: This is a retrospective cohort study of children admitted following CHS between June 1, 2014, and September 30, 2014. Nephrotoxins were defined according to the Nephrotoxic Injury Negated by Just-in-time-Action (NINJA) collaborative; high nephrotoxin exposure was defined as receipt of ≥3 nephrotoxins concurrently. AKI was diagnosed according to KDIGO creatinine criteria. Severe AKI was defined as KDIGO stage ≥2. Poisson models were used to compute adjusted relative risk (aRR) of high nephrotoxin exposure for AKI.RESULTS: One hundred fifty-four children (median age 20.4months, IQR 2.3-59.5) were included. One hundred thirty-one (85.1%) received at least one nephrotoxin; 32 (20.8%) received ≥3 nephrotoxins. The most commonly administered medications were ketorolac (n=74, 48.1%), aspirin (n=62, 40.3%), ibuprofen (n=51, 33.1%), vancomycin (n=39, 25.3%), piperacillin/tazobactam (n=35, 22.7%), and enalapril (n=14, 9.1%). AKI occurred more commonly in those exposed to ≥3 nephrotoxins (62.5 vs. 50.8%); this was not statistically significant after adjusting for confounders (aRR=1.2, 95% CI 0.9-1.7). Severe AKI was similar between those with and without high nephrotoxin exposure (21.9 vs. 19.7%, p=0.78).CONCLUSIONS: Nephrotoxin use is common following pediatric CHS. While we found no association between high nephrotoxin exposure and AKI, this may be related to the multifactorial nature of AKI in this population. For many common nephrotoxins, less injurious agents exist and nephrotoxin exposure may represent a modifiable risk factor for AKI.
View details for PubMedID 29987455
Electronic Health Record-Enabled Big-Data Approaches to Nephrotoxin-Associated Acute Kidney Injury Risk Prediction.
Nephrotoxin-associated acute kidney injury (NTx-AKI) has become one of the most common causes of AKI among hospitalized adults and children; across acute and intensive care populations, exposure to nephrotoxins accounts for 15-25% of AKI. Although some interventions have shown promise in observational studies, no treatments currently exist for NTx-AKI once it occurs. Thus, nearly all effective strategies are aimed at prevention. The primary obstacle to prevention is risk prediction and the determination of which patients are more likely to develop NTx-AKI when exposed to medications with nephrotoxic potential. Historically, traditional statistical modeling has been applied to previously recognized clinical risk factors to identify predictors of NTx-AKI. However, increased electronic health record adoption and the evolution of "big-data" approaches to predictive analytics may offer a unique opportunity to prevent NTx-AKI events. This article describes prior and current approaches to NTx-AKI prediction and offers three novel use cases for electronic health record-enabled NTx-AKI forecasting and risk profiling. This article is protected by copyright. All rights reserved.
View details for PubMedID 29885015
Long-Term Consequences of Acute Kidney Injury in Children
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
2018; 13 (5): 677–78
View details for PubMedID 29678894
View details for PubMedCentralID PMC5969471
Failure to Improve Renal Function Following VAD Placement Predicts Renal Injury and Chronic Kidney Disease Following Cardiac Transplant
ELSEVIER SCIENCE INC. 2018: S117–S118
View details for Web of Science ID 000429934300274
CHILDREN TOLERATE INTRADIALYTIC ORAL NUTRITION
JOURNAL OF RENAL CARE
2018; 44 (1): 38–43
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
Acute Kidney Injury and Big Data
ACUTE KIDNEY INJURY - BASIC RESEARCH AND CLINICAL PRACTICE
2018; 193: 55–67
The recognition of a standardized, consensus definition for acute kidney injury (AKI) has been an important milestone in critical care nephrology, which has facilitated innovation in prevention, quality of care, and outcomes research among the growing population of hospitalized patients susceptible to AKI. Concomitantly, there have been substantial advances in "big data" technologies in medicine, including electronic health records (EHR), data registries and repositories, and data management and analytic methodologies. EHRs are increasingly being adopted, clinical informatics is constantly being refined, and the field of EHR-enabled care improvement and research has grown exponentially. While these fields have matured independently, integrating the two has the potential to redefine and integrate AKI-related care and research. AKI is an ideal condition to exploit big data health care innovation for several reasons: AKI is common, increasingly encountered in hospitalized settings, imposes meaningful risk for adverse events and poor outcomes, has incremental cost implications, and has been plagued by suboptimal quality of care. In this concise review, we discuss the potential applications of big data technologies, particularly modern EHR platforms and health data repositories, to transform our capacity for AKI prediction, detection, and care quality.
View details for DOI 10.1159/000484963
View details for Web of Science ID 000435333400007
View details for PubMedID 29393191
Acute Kidney Injury in Children
ADVANCES IN CHRONIC KIDNEY DISEASE
2017; 24 (6): 380–87
View details for DOI 10.1053/j.ackd.2017.09.007
View details for Web of Science ID 000418988700007
Acute kidney injury in pediatric patients
BEST PRACTICE & RESEARCH-CLINICAL ANAESTHESIOLOGY
2017; 31 (3): 427–39
View details for DOI 10.1016/j.bpa.2017.08.007
View details for Web of Science ID 000418098100012
The Effect of Intradialytic Intralipid Therapy in Pediatric Hemodialysis Patients.
Journal of renal nutrition
2017; 27 (2): 132-137
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
Fluid overload independent of acute kidney injury predicts poor outcomes in neonates following congenital heart surgery.
Pediatric nephrology (Berlin, Germany)
Fluid overload (FO) is common after neonatal congenital heart surgery and may contribute to mortality and morbidity. It is unclear if the effects of FO are independent of acute kidney injury (AKI).This was a retrospective cohort study which examined neonates (age < 30 days) who underwent cardiopulmonary bypass in a university-affiliated children's hospital between 20 October 2010 and 31 December 2012. Demographic information, risk adjustment for congenital heart surgery score, surgery type, cardiopulmonary bypass time, cross-clamp time, and vasoactive inotrope score were recorded. FO [(fluid in-out)/pre-operative weight] and AKI defined by Kidney Disease Improving Global Outcomes serum creatinine criteria were calculated. Outcomes were all-cause, in-hospital mortality and median postoperative hospital and intensive care unit lengths of stay.Overall, 167 neonates underwent cardiac surgery using cardiopulmonary bypass in the study period, of whom 117 met the inclusion criteria. Of the 117 neonates included in the study, 76 (65%) patients developed significant FO (>10%), and 25 (21%) developed AKI ≥ Stage 2. When analyzed as FO cohorts (< 10%,10-20%, > 20% FO), patients with greater FO were more likely to have AKI (9.8 vs. 18.2 vs. 52.4%, respectively, with AKI ≥ stage 2; p = 0.013) and a higher vasoactive-inotrope score, and be premature. In the multivariable regression analyses of patients without AKI, FO was independently associated with hospital and intensive care unit lengths of stay [0.322 extra days (p = 0.029) and 0.468 extra days (p < 0.001), respectively, per 1% FO increase). In all patients, FO was also associated with mortality [odds ratio 1.058 (5.8% greater odds of mortality per 1% FO increase); 95% confidence interval 1.008,1.125;p = 0.032].Fluid overload is an important independent contributor to outcomes in neonates following congenital heart surgery. Careful fluid management after cardiac surgery in neonates with and without AKI is warranted.
View details for PubMedID 29128923
Incidence, risk factors, and outcomes of acute kidney injury in adults undergoing surgery for congenital heart disease.
Cardiology in the young
Acute kidney injury after cardiac surgery is a frequent and serious complication among children with congenital heart disease (CHD) and adults with acquired heart disease; however, the significance of kidney injury in adults after congenital heart surgery is unknown. The primary objective of this study was to determine the incidence of acute kidney injury after surgery for adult CHD. Secondary objectives included determination of risk factors and associations with clinical outcomes.This single-centre, retrospective cohort study was performed in a quaternary cardiovascular ICU in a paediatric hospital including all consecutive patients ⩾18 years between 2010 and 2013.Data from 118 patients with a median age of 29 years undergoing cardiac surgery were analysed. Using Kidney Disease: Improving Global Outcome creatinine criteria, 36% of patients developed kidney injury, with 5% being moderate to severe (stage 2/3). Among higher-complexity surgeries, incidence was 59%. Age ⩾35 years, preoperative left ventricular dysfunction, preoperative arrhythmia, longer bypass time, higher Risk Adjustment for Congenital Heart Surgery-1 category, and perioperative vancomycin use were significant risk factors for kidney injury development. In multivariable analysis, age ⩾35 years and vancomycin use were significant predictors. Those with kidney injury were more likely to have prolonged duration of mechanical ventilation and cardiovascular ICU stay in the univariable regression analysis.We demonstrated that acute kidney injury is a frequent complication in adults after surgery for CHD and is associated with poor outcomes. Risk factors for development were identified but largely not modifiable. Further investigation within this cohort is necessary to better understand the problem of kidney injury.
View details for PubMedID 27869053
Management of Peritoneal Dialysis Catheters That Erode Into Bowel: Two Pediatric Case Reports and a Review of the Literature
PERITONEAL DIALYSIS INTERNATIONAL
2016; 36 (6): 680-700
Erosion of peritoneal dialysis (PD) catheters into the intestine is a rare complication of PD. Herein, we convey the first reports of 2 pediatric patients undergoing PD who were found to have the catheter eroding into their intestines. They were treated minimally with catheter removal and antibiotics. Definitive repair of the intestinal injury was not performed. These are the first pediatric patients reported with PD catheter erosion. Perforating injuries may be self-limiting, and therefore a more minimal approach may be considered in certain patient populations who do not express overt signs of peritonitis or illness.
View details for DOI 10.3747/pdi.2016.00029
View details for Web of Science ID 000389655100016
View details for PubMedID 27903851
Theophylline Population Pharmacokinetics and Dosing in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass.
Journal of clinical pharmacology
2016; 56 (9): 1084-1093
Children undergoing cardiac surgery requiring cardiopulmonary bypass (CPB) frequently develop acute kidney injury due to renal ischemia. Theophylline, which improves renal perfusion via adenosine receptor inhibition, is a potential targeted therapy. However, children undergoing cardiac surgery and CPB commonly have alterations in drug pharmacokinetics. To help understand optimal aminophylline (salt formulation of theophylline) dosing strategies in this population, a population-based pharmacokinetic model was developed using nonlinear mixed-effects modeling (NONMEM) from 71 children (median age: 5 months [90% range: 1 week - 10 years]) who underwent cardiac surgery requiring CPB and received aminophylline as part of a previous randomized controlled trial. A one-compartment model with linear elimination adequately described the pharmacokinetics of theophylline. Weight scaled via allometry was a significant predictor of clearance and volume. In addition, allometric scaled clearance increased with age implemented as a power maturation function. Compared to prior reports in non-cardiac children, theophylline clearance was markedly reduced across age. Applying the final population pharmacokinetic model, optimized empiric dosing regimens were developed via Monte Carlo simulations. Doses 50-75% lower than those recommended in non-cardiac children were needed to achieve target serum concentrations of 5-10 mg/L. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/jcph.697
View details for PubMedID 26712558
The authors reply.
Pediatric critical care medicine
2016; 17 (8): 814-815
View details for DOI 10.1097/PCC.0000000000000841
View details for PubMedID 27500628
Letter to the Editor regarding "Arrhythmias in the paediatric ICU: a prospective study of the rates and predictors of arrhythmias in children without underlying cardiac disease" by Cassel-Choudhury et al.
Cardiology in the young
View details for PubMedID 27418191
Electronic Health Record-Enabled Research in Children Using the Electronic Health Record for Clinical Discovery.
Pediatric clinics of North America
2016; 63 (2): 251-268
Initially described more than 50 years ago, electronic health records (EHRs) are now becoming ubiquitous throughout pediatric health care settings. The confluence of increased EHR implementation and the exponential growth of digital data within them, the development of clinical informatics tools and techniques, and the growing workforce of experienced EHR users presents new opportunities to use EHRs to augment clinical discovery and improve pediatric patient care. This article reviews the basic concepts surrounding EHR-enabled research and clinical discovery, including the types and fidelity of EHR data elements, EHR data validation/corroboration, and the steps involved in analytical interrogation.
View details for DOI 10.1016/j.pcl.2015.12.002
View details for PubMedID 27017033
Dexmedetomidine Is Associated With Lower Incidence of Acute Kidney Injury After Congenital Heart Surgery.
Pediatric critical care medicine
2016; 17 (2): 128-134
Recent data have suggested an association between the use of dexmedetomidine and a decreased incidence of acute kidney injury in adult patients after cardiopulmonary bypass. However, no study has focused on this association among pediatric populations where the incidence of acute kidney injury is particularly high and of critical significance. The primary objective of this study was to assess the relationship between the use of postoperative dexmedetomidine and the incidence of acute kidney injury in pediatric patients undergoing cardiopulmonary bypass. The secondary objective was to determine whether there was an association between dexmedetomidine use and duration of mechanical ventilation or cardiovascular ICU stay.Single-center retrospective matched cohort study.A 20-bed quaternary cardiovascular ICU in a university-based pediatric hospital in California.Children less than 18 years old admitted after cardiac surgery with cardiopulmonary bypass between January 1, 2012, and May 31, 2014.None.Data from a cohort of 102 patients receiving dexmedetomidine during the first postoperative day after cardiac surgery were compared to an age- and procedure-matched cohort not receiving dexmedetomidine. Cohorts had similar baseline and demographic characteristics. Patients receiving dexmedetomidine were less likely to develop acute kidney injury (24% vs 36%; odds ratio, 0.54; 95% CI, 0.29-0.99; p = 0.046). After adjusting for age, bypass time, nephrotoxin use, and vasoactive inotropic score, the use of dexmedetomidine was associated with a lower incidence of acute kidney injury with adjusted odds ratio of 0.43 (95% CI, 0.27-0.98; p = 0.048). There was no difference between the cohorts with respect to the duration of mechanical duration (1 d each; p = 0.98) or cardiovascular ICU stays (5 vs 6 d; p = 0.91).The use of a dexmedetomidine infusion in pediatric patients after congenital heart surgery was associated with a decreased incidence of acute kidney injury; however, it was not associated with changes in clinical outcomes. Further prospective study is necessary to validate these findings.
View details for DOI 10.1097/PCC.0000000000000611
View details for PubMedID 26673841
A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass.
Pediatric critical care medicine
2016; 17 (2): 135-143
Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass.Single-center, double-blinded, placebo-controlled, randomized clinical trial.Tertiary center, pediatric cardiovascular ICU.A total of 144 children after congenital heart surgery with cardiopulmonary bypass.Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours.The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30).In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.
View details for DOI 10.1097/PCC.0000000000000612
View details for PubMedID 26669642
A Hyperpigmented Reticular Rash in a Patient on Peritoneal Dialysis.
Peritoneal dialysis international
2016; 36 (6): 699-700
Chronically ill patients often develop uncommon exam findings. A 16-year-old female with end-stage renal disease secondary to immune complex-mediated glomerulonephritis on peritoneal dialysis (PD) developed a pruritic, hyperpigmented reticular rash on her abdomen, sparing the PD catheter insertion site. The rash appeared approximately 6 weeks after initiating PD. She used a heating pad nightly during PD for dialysis drain pain. Testing for systemic and autoimmune disease was negative. She was referred to dermatology, where the diagnosis of erythema ab igne (EAI), a well-described but less well-known hyperpigmented reticular cutaneous eruption caused by chronic exposure to low levels of infrared heat, was confirmed. The eruption is typically painless but is often pruritic. Common sources of heat include fires, stoves, portable heaters, heating pads, and laptop computers. The association between EAI and PD is unknown. Our patient discontinued the heating pad and her rash resolved.
View details for PubMedID 27903857
Applications for detection of acute kidney injury using electronic medical records and clinical information systems: workgroup statements from the 15(th) ADQI Consensus Conference.
Canadian journal of kidney health and disease
2016; 3: 9-?
Electronic medical records and clinical information systems are increasingly used in hospitals and can be leveraged to improve recognition and care for acute kidney injury. This Acute Dialysis Quality Initiative (ADQI) workgroup was convened to develop consensus around principles for the design of automated AKI detection systems to produce real-time AKI alerts using electronic systems. AKI alerts were recognized by the workgroup as an opportunity to prompt earlier clinical evaluation, further testing and ultimately intervention, rather than as a diagnostic label. Workgroup members agreed with designing AKI alert systems to align with the existing KDIGO classification system, but recommended future work to further refine the appropriateness of AKI alerts and to link these alerts to actionable recommendations for AKI care. The consensus statements developed in this review can be used as a roadmap for development of future electronic applications for automated detection and reporting of AKI.
View details for DOI 10.1186/s40697-016-0100-2
View details for PubMedID 26925245
Acute kidney injury in the era of big data: the 15(th) Consensus Conference of the Acute Dialysis Quality Initiative (ADQI).
Canadian journal of kidney health and disease
2016; 3: 5-?
The world is immersed in "big data". Big data has brought about radical innovations in the methods used to capture, transfer, store and analyze the vast quantities of data generated every minute of every day. At the same time; however, it has also become far easier and relatively inexpensive to do so. Rapidly transforming, integrating and applying this large volume and variety of data are what underlie the future of big data. The application of big data and predictive analytics in healthcare holds great promise to drive innovation, reduce cost and improve patient outcomes, health services operations and value. Acute kidney injury (AKI) may be an ideal syndrome from which various dimensions and applications built within the context of big data may influence the structure of services delivery, care processes and outcomes for patients. The use of innovative forms of "information technology" was originally identified by the Acute Dialysis Quality Initiative (ADQI) in 2002 as a core concept in need of attention to improve the care and outcomes for patients with AKI. For this 15(th) ADQI consensus meeting held on September 6-8, 2015 in Banff, Canada, five topics focused on AKI and acute renal replacement therapy were developed where extensive applications for use of big data were recognized and/or foreseen. In this series of articles in the Canadian Journal of Kidney Health and Disease, we describe the output from these discussions.
View details for DOI 10.1186/s40697-016-0103-z
View details for PubMedID 26925244
Establishing a continuum of acute kidney injury - tracing AKI using data source linkage and long-term follow-up: Workgroup Statements from the 15th ADQI Consensus Conference.
Canadian journal of kidney health and disease
2016; 3: 13-?
Acute kidney injury (AKI) is independently associated with the development of chronic kidney disease, endstage kidney disease and increased all-cause and cardiovascular-specific mortality. The severity of the renal insult and the development of multiple AKI episodes increase the risk of occurrence of these outcomes. Despite these long-term effects, only a minority of patients receive nephrologist follow up after an episode of AKI; those that do may have improved outcomes. Furthermore, relatively simple quality improvement strategies have the potential to change this status quo.On this background, a working group of the 15(th) Acute Dialysis Quality Initiative (ADQI) conference applied the consensus-building process informed by review of English language articles identified through PubMed search to address questions related to the opportunities, methodological requirements and barriers for longitudinal follow-up of patients with AKI in the era of electronic health records and Big Data.Four consensus statements answering the key questions identified by the working group are developed.We have identified minimal data elements and potential data sources necessary to trace the natural history of patients from onset of AKI to long-term outcome. Minimum infrastructure and key barriers to achieving these goals are outlined together with proposed solutions.
View details for DOI 10.1186/s40697-016-0102-0
View details for PubMedID 26925249
Impact of electronic-alerting of acute kidney injury: workgroup statements from the 15(th) ADQI Consensus Conference.
Canadian journal of kidney health and disease
2016; 3: 10-?
Among hospitalized patients, acute kidney injury is common and associated with significant morbidity and risk for mortality. The use of electronic health records (EHR) for prediction and detection of this important clinical syndrome has grown in the past decade. The steering committee of the 15(th) Acute Dialysis Quality Initiative (ADQI) conference dedicated a workgroup with the task of identifying elements that may impact the course of events following Acute Kidney Injury (AKI) e-alert.Following an extensive, non-systematic literature search, we used a modified Delphi process to reach consensus regarding several aspects of the utilization of AKI e-alerts.Topics discussed in this workgroup included progress in evidence base practices, the characteristics of an optimal e-alert, the measures of efficacy and effectiveness, and finally what responses would be considered best practices following AKI e-alerts. Authors concluded that the current evidence for e-alert system efficacy, although growing, remains insufficient. Technology and human-related factors were found to be crucial elements of any future investigation or implementation of such tools. The group also concluded that implementation of such systems should not be done without a vigorous plan to evaluate the efficacy and effectiveness of e-alerts. Efficacy and effectiveness of e-alerts should be measured by context-specific process and patient outcomes. Finally, the group made several suggestions regarding the clinical decision support that should be considered following successful e-alert implementation.This paper reflects the findings of a non-systematic review and expert opinion.We recommend implementation of the findings of this workgroup report for use of AKI e-alerts.
View details for DOI 10.1186/s40697-016-0101-1
View details for PubMedID 26925246
Perioperative fluid management and postoperative hyponatremia in children
2016; 31 (1): 53-60
Intravenous (IV) fluids are used ubiquitously when children undergo surgical procedures. Until recently, Holliday and Segar's guidelines for calculating maintenance fluids dictated fluid management strategies in postoperative pediatric patients. An increased recognition of hospital-acquired hyponatremia and its associated morbidity has led to a critical re-examination of IV fluid management in this population. Postsurgical patients are at high risk of developing hyponatremia due to the presence of non-osmotic stimuli for antidiuretic hormone release. Recent studies have established that, as they are administered in current practice, hypotonic maintenance fluids are associated with increased rates of hyponatremia. The best available data demonstrate that administration of isotonic fluid reduces hyponatremic risk. In this review, we discuss the collective data available on the subject and offer guidelines for fluid management and therapeutic monitoring.
View details for DOI 10.1007/s00467-015-3081-y
View details for Web of Science ID 000365100500005
View details for PubMedID 25784018
Optimizing administrative datasets to examine acute kidney injury in the era of big data: workgroup statement from the 15(th) ADQI Consensus Conference.
Canadian journal of kidney health and disease
2016; 3: 12-?
The purpose of this review is to report how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to address knowledge gaps in the field.1) To review the existing evidence-base on how AKI is coded across administrative datasets, 2) To identify limitations, gaps in knowledge, and major barriers to scientific progress in AKI related to coding in administrative data, 3) To discuss how administrative data for AKI might be enhanced to enable "communication" and "translation" within and across administrative jurisdictions, and 4) To suggest how administrative databases might be configured to inform 'registry-based' pragmatic studies.Literature review of English language articles through PubMed search for relevant AKI literature focusing on the validation of AKI in administrative data or used administrative data to describe the epidemiology of AKI.Acute Dialysis Quality Initiative (ADQI) Consensus Conference September 6-7(th), 2015, Banff, Canada.Hospitalized patients with AKI.The coding structure for AKI in many administrative datasets limits understanding of true disease burden (especially less severe AKI), its temporal trends, and clinical phenotyping. Important opportunities exist to improve the quality and coding of AKI data to better address critical knowledge gaps in AKI and improve care.A modified Delphi consensus building process consisting of review of the literature and summary statements were developed through a series of alternating breakout and plenary sessions.Administrative codes for AKI are limited by poor sensitivity, lack of standardization to classify severity, and poor contextual phenotyping. These limitations are further hampered by reduced awareness of AKI among providers and the subjective nature of reporting. While an idealized definition of AKI may be difficult to implement, improving standardization of reporting by using laboratory-based definitions and providing complementary information on the context in which AKI occurs are possible. Administrative databases may also help enhance the conduct of and inform clinical or registry-based pragmatic studies.Data sources largely restricted to North American and Europe.Administrative data are rapidly growing and evolving, and represent an unprecedented opportunity to address knowledge gaps in AKI. Progress will require continued efforts to improve awareness of the impact of AKI on public health, engage key stakeholders, and develop tangible strategies to reconfigure infrastructure to improve the reporting and phenotyping of AKI. WHY IS THIS REVIEW IMPORTANT?: Rapid growth in the size and availability of administrative data has enhanced the clinical study of acute kidney injury (AKI). However, significant limitations exist in coding that hinder our ability to better understand its epidemiology and address knowledge gaps. The following consensus-based review discusses how administrative data have been used to study AKI, identify current limitations, and suggest how these data sources might be enhanced to improve the future study of this disease. WHAT ARE THE KEY MESSAGES?: The current coding structure of administrative data is hindered by a lack of sensitivity, standardization to properly classify severity, and limited clinical phenotyping. These limitations combined with reduced awareness of AKI and the subjective nature of reporting limit understanding of disease burden across settings and time periods. As administrative data become more sophisticated and complex, important opportunities to employ more objective criteria to diagnose and stage AKI as well as improve contextual phenotyping exist that can help address knowledge gaps and improve care.
View details for DOI 10.1186/s40697-016-0098-5
View details for PubMedID 26925248
Exploring Value in Congenital Heart Disease: An Evaluation of Inpatient Admissions.
Congenital heart disease
2015; 10 (6): E278-87
Understanding value provides an important context for improvement. However, most health care models fail to measure value. Our objective was to categorize inpatient encounters within an academic congenital heart program based on clinical outcome and the cost to achieve the outcome (value). We aimed to describe clinical and nonclinical features associated with value.We defined hospital encounters based on outcome per resource utilized. We performed principal component and cluster analysis to classify encounters based on mortality, length of stay, hospital cost and revenue into six classes. We used nearest shrunken centroid to identify discriminant features associated with the cluster-derived classes. These features underwent hierarchical clustering and multivariate analysis to identify features associated with each class.We analyzed all patients admitted to an academic congenital heart program between September 1, 2009, and December 31, 2012.A total of 2658 encounters occurred during the study period. Six classes were categorized by value. Low-performing value classes were associated with greater institutional reward; however, encounters with higher-performing value were associated with a loss in profitability. Encounters that included insertion of a pediatric ventricular assist device (log OR 2.5 [95% CI, 1.78 to 3.43]) and acquisition of a hospital-acquired infection (log OR 1.42 [95% CI, 0.99 to 1.87]) were risk factors for inferior health care value.Among the patients in our study, institutional reward was not associated with value. We describe a framework to target quality improvement and resource management efforts that can benefit patients, institutions, and payers alike.
View details for DOI 10.1111/chd.12290
View details for PubMedID 26219731
CRIT-LINE: a noninvasive tool to monitor hemoglobin levels in pediatric hemodialysis patients
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
44-h ambulatory blood pressure monitoring: revealing the true burden of hypertension in pediatric hemodialysis patients.
2015; 30 (4): 653-660
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
Utility of Clinical Biomarkers to Predict Central Line-associated Bloodstream Infections After Congenital Heart Surgery.
Pediatric infectious disease journal
2015; 34 (3): 251-254
Central line associated bloodstream infections is an important contributor of morbidity and mortality in children recovering from congenital heart surgery. The reliability of commonly used biomarkers to differentiate these patients have not been specifically studied.This was a retrospective cohort study in a university-affiliated children's hospital examining all patients with congenital or acquired heart disease admitted to the cardiovascular intensive care unit following cardiac surgery who underwent evaluation for a catheter-associated bloodstream infection.Among 1260 cardiac surgeries performed, 451 encounters underwent an infection evaluation post-operatively. Twenty-five instances of CLABSI and 227 instances of a negative infection evaluation were the subject of analysis. Patients with CLABSI tended to be younger (1.34 vs 4.56 years, p = 0.011) and underwent more complex surgery (RACHS-1 score 3.79 vs 3.04, p = 0.039). The two groups were indistinguishable in WBC, PMNs and band count at the time of their presentation. On multivariate analysis, CLABSI was associated with fever (adjusted OR 4.78; 95% CI, 1.6 to 5.8) and elevated CRP (adjusted OR 1.28; 95% CI, 1.09 to 1.68) after adjusting for differences between the two groups. Receiver operating characteristic analysis demonstrated the discriminatory power of both fever and CRP (area under curve 0.7247, 95% CI, 0.42 to 0.74 and 0.58, 95% CI 0.4208 to 0.7408). We calculated multilevel likelihood ratios for a spectrum of temperature and CRP values.We found commonly used serum biomarkers such as fever and CRP not to be helpful discriminators in patients following congenital heart surgery.
View details for DOI 10.1097/INF.0000000000000553
View details for PubMedID 25232780
Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in Critically Ill Children (AWARE): study protocol for a prospective observational study
Acute kidney injury (AKI) is associated with poor outcome in critically ill children. While data extracted from retrospective study of pediatric populations demonstrate a high incidence of AKI, the literature lacks focused and comprehensive multicenter studies describing AKI risk factors, epidemiology, and outcome. Additionally, very few pediatric studies have examined novel urinary biomarkers outside of the cardiopulmonary bypass population.This is a prospective observational study. We anticipate collecting data on over 5000 critically ill children admitted to 31 pediatric intensive care units (PICUs) across the world during the calendar year of 2014. Data will be collected for seven days on all children older than 90 days and younger than 25 years without baseline stage 5 chronic kidney disease, chronic renal replacement therapy, and outside of 90 days of a kidney transplant or from surgical correction of congenital heart disease. Data to be collected includes demographic information, admission diagnoses and co-morbidities, and details on fluid and vasoactive resuscitation used. The renal angina index will be calculated integrating risk factors and early changes in serum creatinine and fluid overload. On days 2-7, all hemodynamic and pertinent laboratory values will be captured focusing on AKI pertinent values. Daily calculated values will include % fluid overload, fluid corrected creatinine, and KDIGO AKI stage. Urine will be captured twice daily for biomarker analysis on Days 0-3 of admission. Biomarkers to be measured include neutrophil gelatinase lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (l-FABP), and interleukin-18 (IL-18). The primary outcome to be quantified is incidence rate of severe AKI on Day 3 (Day 3-AKI). Prediction of Day 3-AKI by the RAI and after incorporation of biomarkers with RAI will be analyzed.The Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) study, creates the first prospective international pediatric all cause AKI data warehouse and biologic sample repository, providing a broad and invaluable resource for critical care nephrologists seeking to study risk factors, prediction, identification, and treatment options for a disease syndrome with high associated morbidity affecting a significant proportion of hospitalized children.ClinicalTrials.gov: NCT01987921.
View details for DOI 10.1186/s12882-015-0016-6
View details for Web of Science ID 000350789800001
View details for PubMedID 25882434
Reply: To PMID 23998517.
journal of pediatrics
2014; 165 (3): 644-645
View details for DOI 10.1016/j.jpeds.2014.05.055
View details for PubMedID 25015572
Whole-body single-frequency bioimpedance analysis in pediatric hemodialysis patients
2014; 29 (8): 1417-1423
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
Association between Maintenance Fluid Tonicity and Hospital-Acquired Hyponatremia.
journal of pediatrics
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
Two-point normalized protein catabolic rate overestimates nPCR in pediatric hemodialysis patients
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
Hypertension Screening During Ambulatory Pediatric Visits in the United States, 2000-2009
2012; 130 (4): 604-610
Hypertension occurs in 2% to 5% of children in the United States, and its prevalence has increased during the obesity epidemic. There is no consensus among professional organizations about how frequently blood pressure should be measured in children >3 years old. The purpose of this study was to estimate the frequency of hypertension screening during ambulatory pediatric visits in the United States and to determine patient- and provider-level factors associated with screening during visits specifically for preventive care.We analyzed data from a nationally representative sample of ambulatory visits by using the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey from 2000 through 2009. In the subset of visits involving patients aged 3 to 18 years, we estimated the frequency of screening during all visits, preventive visits, and preventive visits in which overweight/obesity was diagnosed. We used multivariable logistic regression to identify patient- and provider-level factors associated with screening.Hypertension screening occurred during 35% of ambulatory pediatric visits, 67% of preventive visits, and 84% of preventive visits in which overweight/obesity was diagnosed. Between 2000 and 2009, the frequency of screening increased in all visits and in preventive visits. Factors independently associated with screening included older age and overweight/obesity diagnosis.Providers do not measure blood pressure in two-thirds of pediatric visits and one-third of pediatric preventive visits. Providers may understand the importance of screening among overweight/obese children; however, efforts to encourage routine screening, particularly in young children, may be needed.
View details for DOI 10.1542/peds.2011-3888
View details for Web of Science ID 000309412100043
View details for PubMedID 22987883
Rituximab treatment for recurrence of nephrotic syndrome in a pediatric patient after renal transplantation for congenital nephrotic syndrome of Finnish type
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
Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss
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
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
Disseminated Intravascular Coagulation Due to IgM-Mediated Autoimmune Hemolytic Anemia
PEDIATRIC BLOOD & CANCER
2011; 57 (2): 329-331
Disseminated intravascular coagulation (DIC) due to red cell hemolysis has been previously attributed to transfusion-related hemolytic reactions, but not to autoimmune hemolytic anemia. We report a case of DIC in a child with complement-fixing IgM-mediated cold-agglutinin autoimmune hemolysis, which resulted in arterial thrombosis and gangrene of the upper and lower extremities.
View details for DOI 10.1002/pbc.23024
View details for PubMedID 21671368
Role of Twenty-Four-Hour Ambulatory Blood Pressure Monitoring in Children on Dialysis
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
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
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
Protein microarrays identify antibodies to protein kinase C zeta that are associated with a greater risk of allograft loss in pediatric renal transplant recipients
2009; 76 (12): 1277-1283
Antibodies to human leukocyte antigens (HLAs) are a risk factor for acute renal allograft rejection and loss. The role of non-HLAs and their significance to allograft rejection have gained recent attention. Here, we applied protein microarray technology, with the capacity to simultaneously identify 5056 potential antigen targets, to assess non-HLA antibody formation in 15 pediatric renal transplant recipients during allograft rejection. Comparison of the pre- and post-transplant serum identified de novo antibodies to 229 non-HLA targets, 36 of which were present in multiple patients at allograft rejection. On the basis of its reactivity, protein kinase Czeta (PKCzeta) was selected for confirmatory testing and clinical study. Immunohistochemical analysis found PKCzeta both within the renal tissue and infiltrating lymphocytes at rejection. Patients who had an elevated anti-PKCzeta titer developed rejection, which was significantly more likely to result in graft loss. The absence of C4d deposition in patients with high anti-PKCzeta titers suggests that it is a marker of severe allograft injury rather than itself being pathogenic. Presumably, critical renal injury and inflammation associated with this rejection subtype lead to the immunological exposure of PKCzeta with resultant antibody formation. Prospective assessment of serum anti-PKCzeta levels at allograft rejection will be needed to confirm these results.
View details for DOI 10.1038/ki.2009.384
View details for Web of Science ID 000272230400009
View details for PubMedID 19812540
Steroid-Free Immunosuppression in Pediatric Renal Transplantation: Rationale Outcomes Following Conversion to Steroid Based Therapy
2009; 87 (11): 1744-1748
Short-term outcomes using steroid-free immunosuppression after renal transplantation have been promising. No studies have examined the incidence of and reasons for steroid-avoidance protocol failures.We present a single-center analysis of steroid-free immunosuppression failures among 129 pediatric renal transplant recipients with mean follow-up of 5 years. We analyzed causes for failure and examined reasons for conversion to steroid-based therapy. We compared actual patient and allograft survival and allograft function in the cohort of patients who required conversion to steroid-based immunosuppression with that of the cohort maintaining steroid-free immunosuppression.A total of 13.2% (17/129) of patients failed steroid-free immunosuppression. Actual patient survival was equivalent in the two cohorts, 96.4% for the cohort maintaining steroid-free immunosuppression and 94.1% for those requiring conversion. Actual allograft survival was lower in patients requiring conversion to a steroid-based protocol, 76.5% vs. 95.5% (P=0.004). Estimated glomerular filtration rates 12-months and 24-months posttransplant were greater in patients maintaining steroid-free immunosuppression (P=0.003). Most patients (52.9%, 9/17) who broke the steroid-free protocol did so because of refractory acute rejection. The second most common reason was recurrence of glomerulonephritis (GN; 35.3%, 6/17).The failure rate of steroid-free immunosuppression among selective pediatric patients undergoing renal transplantation is low. Patients maintaining steroid-free immunosuppression have better allograft survival and function than those requiring conversion to steroid-based therapy. The most common reasons for failure of steroid-free immunosuppression are recalcitrant or recurrent allograft rejection and recurrent GN; the role of conversion to steroid-based immunosuppression after episodes of acute rejection and recurrent GN requires additional analysis.
View details for DOI 10.1097/TP.0b013e3181a5df60
View details for Web of Science ID 000266889900022
View details for PubMedID 19502970
View details for PubMedCentralID PMC2758080
The challenge for the caregiver of the patient with chronic kidney disease
NEPHROLOGY DIALYSIS TRANSPLANTATION
2008; 23 (12): 3749-3751
View details for DOI 10.1093/ndt/gfn577
View details for Web of Science ID 000261170100005
View details for PubMedID 19028759
Combined liver-kidney transplantation in children: Indications and outcome
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
Liposomal amphotericin B associated with severe hyperphosphatemia
PEDIATRIC INFECTIOUS DISEASE JOURNAL
2008; 27 (1): 77-79
We report 4 patients who developed hyperphosphatemia while receiving liposomal amphotericin B to treat an invasive fungal infection. Resolution of the hyperphosphatemia occurred after transition to amphotericin B lipid complex. This phenomenon may occur more commonly in patients with mild to moderate renal insufficiency.
View details for DOI 10.1097/INF.0b013e31815922a3
View details for PubMedID 18162947
Three cases of suspected antibody-mediated rejection.
View details for PubMedID 18365406