Scott M. Sutherland

Fluid Overload and Mortality in Children Receiving Continuous Renal Replacement Therapy: The Prospective Pediatric Continuous Renal Replacement Therapy Registry

BACKGROUND 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. STUDY DESIGN Prospective observational study. SETTING & PARTICIPANTS 297 children from 13 centers across the United States participating in the Prospective Pediatric CRRT Registry. PREDICTOR 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%. OUTCOME & MEASUREMENTS The primary outcome was survival to pediatric ICU discharge. Data were collected regarding demographics, CRRT parameters, underlying disease process, and severity of illness. RESULTS 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). LIMITATIONS This was an observational study; interventions were not standardized. The relationship between fluid overload and mortality remains an association without definitive evidence of causality. CONCLUSIONS 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.

Complement‐fixing donor‐specific antibodies identified by a novel C1q assay are associated with allograft loss

Sutherland SM, Chen G, Sequeira FA, Lou CD, Alexander SR, Tyan DB. Complement‐fixing donor‐specific antibodies identified by a novel C1q assay are associated with allograft loss. 
Pediatr Transplantation 2012: 16: 12–17.

Evidence-Based Medicine in the EMR Era

Pediatricians facing critical clinical decisions often lack data on which to draw. The authors recently put their institutions electronic medical record to unusual use to inform a decision about anticoagulation in a patient with systemic lupus erythematosus.

AKI in Hospitalized Children: Comparing the pRIFLE, AKIN, and KDIGO Definitions

BACKGROUND AND OBJECTIVES 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Observational, electronic medical record-enabled study of 14,795 hospitalizations at the Lucile Packard Childrens 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. RESULTS 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%. CONCLUSIONS 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.

AKI in hospitalized children: epidemiology and clinical associations in a national cohort.

BACKGROUND AND OBJECTIVES 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. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 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. RESULTS 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. CONCLUSIONS 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.

Hypertension Screening During Ambulatory Pediatric Visits in the United States, 2000–2009

BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Continuous renal replacement therapy in children

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.

Protein microarrays identify antibodies to protein kinase Cζ that are associated with a greater risk of allograft loss in pediatric renal transplant recipients

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.

Role of Twenty-Four-Hour Ambulatory Blood Pressure Monitoring in Children on Dialysis

BACKGROUND AND OBJECTIVES 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). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 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). RESULTS 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. CONCLUSION 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.

Combined liver-kidney transplantation in children: Indications and outcome

Abstract:  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.