Jerome C. Lane

Predictive power of serum cystatin C to detect acute kidney injury and pediatric-modified RIFLE class in children undergoing cardiac surgery

Objective: Acute kidney injury is a frequent and serious complication of cardiopulmonary bypass. In current clinical practice, serum creatinine is used to detect acute kidney injury. Cystatin C is a novel biomarker for kidney function that has been shown to be superior to serum creatinine in predicting acute kidney injury in adults after cardiopulmonary bypass. The aim of this study was to determine whether early cystatin C levels predict acute kidney injury associated with cardiopulmonary bypass in pediatric patients undergoing cardiac surgery and if cystatin C could predict pediatric-modified RIFLE (Risk, Injury, Failure, Loss, End-stage kidney disease) class and renal injury as determined by estimated glomerular filtration rate. We also investigated whether ultrafiltration during cardiopulmonary bypass affects cystatin C levels. Design: Prospective, observational cohort study. Setting: Cardiac intensive care unit in a tertiary, academic pediatric hospital. Patients: One hundred pediatric patients who underwent cardiac surgery involving cardiopulmonary bypass. Interventions: None. Measurements and Main Results: Acute kidney injury was defined as a 50% increase in serum creatinine from a preoperative baseline anytime through postoperative day 4. Severity of acute kidney injury was determined by pediatric RIFLE class using estimated glomerular filtration rate criteria only. Renal injury was also determined by an absolute estimated glomerular filtration rate <80 mL/min/1.73 m2. Cystatin C levels were measured before and after ultrafiltration. Twenty-eight patients (28%) developed acute kidney injury. Cystatin C predicted acute kidney injury as early as 8 hrs after surgery. When applying pediatric RIFLE criteria to the entire study, 30 patients reached “risk” and five developed “injury.” Cystatin C was a good predictor of the development of “injury” (under the receiver operating characteristic curve, 0.834–0.875) and of renal injury by estimated glomerular filtration rate (under the receiver operating characteristic curve, 0.717–0.835) (all p < .05). Cystatin C levels decreased perioperatively and correlated with volume of fluid removed by ultrafiltration. Conclusions: Cystatin C is an early predictor of acute kidney injury in children after cardiopulmonary bypass. Cystatin C is a good predictor of pediatric RIFLE classification and of decreased estimated glomerular filtration rate after cardiopulmonary bypass. Serum cystatin C may be cleared by ultrafiltration.

Blood pressure control in pediatric hemodialysis: the Midwest Pediatric Nephrology Consortium Study

Hypertension is frequent in pediatric patients receiving dialysis, with an especially high rate reported in children on hemodialysis (HD). We performed the present study to assess blood pressure (BP) status and identify risk factors for poor BP control in children on maintenance HD. One month’s dialysis records were collected from 71 subjects receiving HD in ten dialysis units participating in the Midwest Pediatric Nephrology Consortium (MWPNC). For each HD session, data on pre- and posttreatment weights and BPs were recorded. Hypertension, defined as mean BP ≥ 95th percentile, was found in 42 (59%) subjects. Eleven subjects (15.5%) had prehypertension, defined as mean BP between the 90th and 95th percentiles, while 18 subjects (25.3%) had normal BP (<90th percentile). BP significantly decreased at the end of a dialysis session; however, only 15 of 42 hypertensive subjects (35%) normalized their BP. Hypertensive subjects were younger (p = 0.03), had higher serum phosphorus (p = 0.01), and had more elevated posttreatment weight above estimated dry weight (p = 0.02). Logistic regression showed that younger age (p = 0.02) and higher serum phosphorus (p = 0.02) independently predicted hypertensive status. In conclusion, this study emphasizes the difficulty of BP control in pediatric HD patients. Especially poor BP control was found in younger children; those patients who do not reach their posttreatment weight goals, perhaps reflecting their hypervolemic state; and those who have higher serum phosphorus levels.

Prevalence of sleep disturbances in children and adolescents with chronic kidney disease

Although sleep disorders are common in adults with chronic kidney disease, little is known about the prevalence of sleep problems in children and adolescents with chronic kidney disease and their relationship to health-related quality of life measurements. We performed a clinic-based survey of sleep habits and common symptoms of sleep disturbances in 159 school-aged patients with chronic kidney disease. Three patient groups of chronic kidney disease were assessed: group 1, those not on dialysis and not transplanted; group 2, those on dialysis; and group 3, those with a functioning renal allograft. Four symptom domains for sleep disorders were assessed: excessive daytime sleepiness; sleep disordered breathing; restless legs syndrome symptoms; and insufficient sleep. Patients and the parent-proxy also completed the Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales questionnaire. Ninety-three (93) patients (58.5%) had symptoms of a sleep disturbance. The presence of a sleep disturbance correlated with a decrease in health-related quality of life scores that was independent of the chronic kidney disease study group or estimated glomerular filtration rate. We conclude that sleep disturbances are common throughout the spectrum of chronic kidney disease in children and adolescents and are associated with diminished health-related quality of life scores.

Clinical grand rounds: atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.

Pediatric Nephrotic Syndrome: From the Simple to the Complex

Remarkable advances have been made in the past decade in understanding the pathophysiology of idiopathic nephrotic syndrome. Although the initiating events leading to the onset of proteinuria still are not well defined, it has become increasingly clear that many glomerular diseases can be classified as podocytopathies, with injury to the podocyte playing a major role in the development and progression of disease. A complex interaction of immune system mediators, slit diaphragm signal transduction, podocyte injury and conformational change, and mediators of apoptosis and fibrosis determine the extent and nature of proteinuria and progression of glomerulosclerosis. New insights into the pathogenesis of idiopathic nephrotic syndrome likely will lead to innovative therapies and new approaches to management and prevention.

Recognition of elevated blood pressure in an outpatient pediatric tertiary care setting.

OBJECTIVE To assess the prevalence of elevated blood pressure (BP) and its identification among outpatients at a pediatric tertiary care hospital and to assess clinician attitudes towards BP management. STUDY DESIGN A retrospective review was undertaken of electronic medical record data of visits over the course of 1 year to 10 subspecialty divisions and 3 primary care services at an urban tertiary care hospital. Interviews of division/service representatives and a clinician survey on perceived role on BP care, practices, and protocols related to BP management were conducted. Elevated BP was defined as ≥90th percentile (using US references); identification of elevated BP was defined as the presence of appropriate codes in the problem list or visit diagnoses. RESULTS Among 29,000 patients (ages 2-17 years), 70% (those with ≥1 BP measurement) were analyzed. Patients were as follows: 50% male; 42% white, 31% Hispanic, 16% black, 5% Asian, and 5% other/missing; 52% had Medicaid insurance. A total of 64% had normal BPs, 33% had 1-2 elevated BP measurements, and 3% had ≥3 elevated BP measurements. Among those with ≥3 elevated BP measurements, the median frequency of identification by division/service was 17%; the greatest identification was for Kidney Diseases (67%), Wellness & Weight Management (60%), and Cardiology (33%). Among patients with ≥3 elevated BP measurements, 21% were identified vs 7% identified among those with 1-2 increased measurements (P<.001). All clinician survey respondents perceived self-responsibility for identification of elevated BP, but opinions varied for their role in the management of elevated BP. CONCLUSIONS The identification of patients with elevated BP measurements was low. Strategies to increase the identification of elevated BPs in outpatient tertiary care settings are needed.

Practice patterns and approach to kidney biopsy in lupus: a collaboration of the Midwest pediatric nephrology consortium and the childhood arthritis and rheumatology research alliance

BackgroundThere is no clear consensus regarding optimal indications or timing of initial or repeat kidney biopsy in the management of pediatric systemic lupus erythematosus (pSLE).MethodsA web-based survey was designed to assess current practice patterns among pediatric nephrologists and pediatric rheumatologists and distributed to members of Midwest Pediatric Nephrology Consortium (MWPNC) and Childhood Arthritis and Rheumatology Research Alliance (CARRA).ResultsRespondents included 111 rheumatologists and 71 nephrologists from 65 and 34 centers, respectively. Numbers of years in sub-specialty practice were comparable. Rheumatologists and nephrologists frequently collaborate in the care of children with lupus nephritis (LN). More than 90 % of respondents refer patients to each either other after diagnosing LN. Over 60 % describe shared decision making regarding when to perform kidney biopsy and how to interpret biopsy findings. Many pediatric nephrologists consider biopsy to be of higher risk for complication in pSLE and alter their standard pre-or post-biopsy management.ConclusionsIt is uncommon for pediatric nephrologists to manage LN without input from pediatric rheumatologists and vice versa. Consensus exists between specialties in general, and practice differences that exist occur between individual physicians rather than between specialties. A systematic approach to biopsy may result in improved health related outcomes in pSLE.

Extreme Renal Pathology in Alagille Syndrome

INTRODUCTION A lagille syndrome (ALGS) results from mutations in JAG1 and NOTCH2 in the Notch signaling pathway. These mutations clinically manifest in various ways, but ALGS is most commonly characterized by a paucity of bile ducts in the liver. ALGS often involves the kidney, which can be characterized by defects in the glomerular vasculature, podocytes, proximal tubules, and renal dysplasia. In addition, altered lipid metabolism in ALGS can cause mesangial lipidosis in the kidney. Few case reports describe the renal manifestations of ALGS. Here we report an Alagille syndrome patient with renal dysplasia, renal lipidosis, and bile cast nephropathy. This case highlights the spectrum of renal pathologic findings due to Alagille syndrome that can manifest as a result of defects in the Notch signaling pathway.

Hemofiltration circuit use beyond 72 hours in pediatric continuous renal replacement therapy

Introduction During continuous renal replacement therapy (CRRT), hemofiltration circuits ideally are changed after 72 h since tubing integrity and flow rates are not guaranteed after this time interval. This potential risk must be weighed against the risk of hypotension during elective circuit changes in the unstable patient. The aim of this study was to examine the safety of circuits used beyond 72 h in pediatric CRRT. Methods A retrospective chart review of all patients who underwent CRRT at our institution from January 2003 to October 2005 was performed. Procedures were divided into standard (≤72 h) and extended (>72 h) circuit duration groups. Patients who had more than one CRRT procedure (n=13) were excluded from study. Results 71 CRRT procedures were performed for 71 patients. A total of 254 circuits were used, of which 64 (25%) were used for >72 h. For circuits >72 h, the mean duration of use was 5.5 days ± 1.8 (range 4–11). There were no differences between the groups in age (p=0.12), weight (p=0.48), diagnosis (p=0.21), CRRT indication (p=0.07), CRRT mode (p=0.37), anticoagulation (p=0.53), blood flow rate (p=0.06), replacement rate (p=0.50) or dialysate rate (p=0.89). There were no incidents of membrane or tubing rupture in either group. Conclusions Use of hemofiltration circuits beyond 72 h may be safe in pediatric patients undergoing CRRT without increased risk of tubing rupture. Our data suggest a need to redefine the limits of prolonged circuit use in pediatric CRRT.