The first randomized controlled trial in pediatric nephrology: the history of the International Study of Kidney Disease in Children (ISKDC).

The International Study of Kidney Disease in Children (ISKDC), begun in 1966, conducted the first international collaborative randomized blinded controlled trial in pediatric nephrology and one of the first in either pediatrics or nephrology. For this trial, the ISKDC developed the criteria, such as those for response and relapse, used today to describe the clinical course of the nephrotic syndrome, and the trial generated the nephropathologic terminology and criteria which largely remain the current standards. Over an approximately 20-year span, the ISKDC followed the natural history and evaluated the therapeutic effectiveness of therapies in over 500 children with the nephrotic syndrome from three continents. It published 14 peer-reviewed studies and several reports and commentaries, many of which helped create current standards of practice for therapy of childhood nephrotic syndrome and consequently remain highly cited today. The ISKDC continues to be an important model for subsequent collaborative studies and was the impetus for the development of regional and national pediatric nephrology societies leading to the recognition and growth of pediatric nephrology as a separate subspecialty. A higher resolution version of the Graphical abstract is available as Supplementary information.

Surgical outcomes analysis of pediatric peritoneal dialysis catheter function in a rural region.

PURPOSE: The purpose of this study was to analyze the experience with peritoneal dialysis (PD) at a high-volume, single center institution that supports a rural population. METHODS: From 2000 to 2010, 88 children (median age: 1.98 years, [range: 2 days-20.2 years]) received 134 PD catheters for the management of acute and chronic renal failure. The primary outcome of interest was the incidence of primary PD catheter failure (replacement or revision within 60 days). Operative technique, longitudinal outcomes, and time intervals to transplantation were analyzed. RESULTS: Median time to transplant from the institution of dialysis was 1.4 years [range: 0.3-6.4 years]. Primary catheter failure occurred in 24.6% of cases. Infants less than 6 months of age demonstrated an increased incidence of primary catheter failure (p = 0.02). The operative technique for catheter placement was not associated with the incidence of primary failure. Postoperative complications included peritonitis (22.7%), omental plugging (11.9%), pericatheter drainage (9.0%), and exit site infection (3.0%). CONCLUSION: Peritoneal dialysis provides a safe and effective renal replacement therapy for regional pediatric centers that serve a rural population. However, primary catheter failure rates remain high at 24.6%. The surgical technique for placement had no effect on this failure rate in our patient population. Infants less than 6 months of age are at increased risk for primary catheter failure and warrant intensive surveillance.

Paediatric acid-base disorders: A case-based review of procedures and pitfalls.

Acid-base disorders occur frequently in paediatric patients. Despite the perception that their analysis is complex and difficult, a straightforward set of rules is sufficient to interpret even the most complex disorders - provided certain pitfalls are avoided. Using a case-based approach, the present article reviews the fundamental concepts of acid-base analysis and highlights common mistakes and oversights. Specific topics include the proper identification of the primary disorder; distinguishing compensatory changes from additional primary disorders; use of the albumin-corrected anion gap to generate a differential diagnosis for patients with metabolic acidosis; screening for mixed disorders with the delta-delta formula; recognizing the limits of compensation; use of the anion gap to identify 'hidden' acidosis; and the importance of using information from the history and physical examination to identify the specific cause of a patient's acid-base disturbance.

Les troubles de l'équilibre acido-basique sont fréquents chez les patients d'âge pédiatrique. Même si on les croit difficiles et complexes à analyser, des règles simples suffsent pour interpréter même les troubles les plus complexes, pourvu qu'on évite certains écueils.Au moyen d'une approche fondée sur des cas, le présent article contient les concepts fondamentaux de l'analyse acido-basique et fait ressortir des erreurs et des omissions courantes. Les thèmes abordés incluent la bonne détermination du trouble primaire, la distinction entre les changements compensatoires et d'autres troubles primaires, l'utilisation du trou anionique corrigé par l'albumine pour produire un diagnostic différentiel chez les patients ayant une acidose métabolique, le dépistage de troubles mixtes au moyen de la formule delta-delta, la détermination des limites de compensation, l'utilisation du trou anionique pour dépister une acidose « cachée ¼ et l'importance d'utiliser l'information tirée de l'anamnèse et de l'examen physique pour déterminer la cause précise de la perturbation acido-basique du patient.

Predictors of Retention and BMI Loss or Stabilization in Obese Youth Enrolled in a Weight Loss Intervention.

OBJECTIVE: To evaluate predictors for intervention dropout and successful reduction of metabolic syndrome risk factors among obese children enrolled in a short-term, clinic-based weight-loss intervention. DESIGN, SETTING, SUBJECTS: Retrospective database review of 1080 children 8 months-17 y.o. seen a a pediatric obesity clinic. INTERVENTIONS: Behavior modification counseling to induce change in dietary and exercise choices. MAIN OUTCOME MEASURES: 1). Pre-/post-intervention change in body mass index (BMI), waist circumference, blood pressure, glucose, insulin, and cholesterol (LDL, HDL, & total). 2) Predictors of successful decrease in BMI and clinic drop-out. ANALYSIS: Paired t-tests for pre-/post-intervention comparisons. Linear regression to assess predictors of success and predictors of drop-out, with adjustment for age, gender, race, insurance status, and service area. RESULTS: Among children evaluated, adolescent females were most likely to achieve successful decrease in BMI, insulin level, and LDL cholesterol post-intervention. Nearly 40% of children dropped out early in the intervention. Predictors of drop out included age <6y, public insurance status, follow-up scheduled during summer months, and residence in a tertiary service area. CONCLUSIONS: Clinic-based weight loss interventions can lead to successful improvements in BMI and other metabolic parameters in pediatric populations and may be more likely among adolescent females than in younger children or males. Drop-out is common, particularly among younger children, children with public insurance and children scheduled for follow-up in the summer. Identification of these drop-out predictors in individual patients may help in targeting children likely to succeed in short-term, clinic-based, weight-loss interventions.

Evolution of the urinary proteome during human renal development and maturation: variations with gestational and postnatal age.

BACKGROUND: Low birth weight is associated with deficits in nephron number in the infant kidney and increased risk of adulthood hypertension and renal dysfunction. Urinary biomarkers may be potential indicators of renal reserve, but little is known about the influence of gestational and postnatal age on the expression of urinary proteins. The aims of this study were to determine the relationships between selected urinary proteins and renal maturation. We hypothesized that urinary protein patterns would change over time during late nephrogenesis and renal maturation. METHODS: Urine samples were collected at birth and over 12 mo from preterm (33-35 wk) and term (38-40 wk) infants. Candidate urinary proteins were identified by antibody array and quantified with enzyme-linked immunosorbent assay. RESULTS: Preterm infants at birth were found to have relatively elevated levels of insulin-like growth factor binding protein-1, -2, and -6, monocyte chemotactic protein-1, CD14, and sialic acid-binding Ig-like lectin 5. These markers gradually decline to levels similar to those of full-term infants by 2-6 mo of life. In contrast, many urinary markers in healthy full-term infants remain stable over the first year of life. CONCLUSION: Gestational and postnatal age must be considered when evaluating the utility of urinary biomarkers.

A clinical approach to paediatric acid-base disorders.

Acid-base disorders are common in pediatric patients. We present a simple methodology for assessing both simple and complex acid-base disorders that is applicable to patients of all ages, and focus specifically on the usefulness of this approach in the pediatric patient. The application of four simple rules in sequence will define even the most complicated acid-base disturbance. However, because acid-base disorders are manifestations of systemic disorders, the primary value of characterizing them is that each generates a unique differential diagnosis. For each of the cardinal acid base disorders, the common and clinically-relevant causes in pediatric patients are explored. Additional diagnostic tools (including the serum anion gap, the delta-delta, the alveolar-arterial gradient, urine anion gap, and urine chloride), certain easily-recalled mnemonics, and empiric rules of thumb are also useful in specific situations. The treatment of acid-base disturbances is also considered, though treatment is generally best directed at the underlying disorder.

Predictors of retention and BMI loss or stabilization in obese youth enrolled in a weight loss intervention.

OBJECTIVE: To evaluate predictors for intervention dropout and successful reduction of metabolic syndrome risk factors among obese children enrolled in a short-term, clinic-based weight-loss intervention. DESIGN, SETTING, SUBJECTS: Retrospective database review of 1080 children 8 months to 17 years. seen a pediatric obesity clinic. INTERVENTIONS: Behavior modification counseling to induce change in dietary and exercise choices. MAIN OUTCOME MEASURES: (1) Pre-/post-intervention change in body mass index (BMI), waist circumference, blood pressure, glucose, insulin, and cholesterol (LDL, HDL, & total). (2) Predictors of successful decrease in BMI and clinic drop-out. ANALYSIS: Paired t-tests for pre-/post-intervention comparisons. Linear regression to assess predictors of success and predictors of drop-out, with adjustment for age, gender, race, insurance status, and service area. RESULTS: Among children evaluated, adolescent females were most likely to achieve successful decrease in BMI, insulin level, and LDL cholesterol post-intervention. Nearly 40% of children dropped out early in the intervention. Predictors of drop out included age <6 years, public insurance status, follow-up scheduled during summer months, and residence in a tertiary service area. CONCLUSIONS: Clinic-based weight loss interventions can lead to successful improvements in BMI and other metabolic parameters in pediatric populations and may be more likely among adolescent females than in younger children or males. Drop-out is common, particularly among younger children, children with public insurance and children scheduled for follow-up in the summer. Identification of these drop-out predictors in individual patients may help in targeting children likely to succeed in short-term, clinic-based, weight-loss interventions.

Factors influencing pediatric nephrology trainee entry into the workforce.

BACKGROUND AND OBJECTIVES: Emerging needs in pediatric nephrology (PN) have made the number of nephrologists entering the workforce of critical importance. This study aimed to discern factors that influence PN fellows to choose their career path and decide to enter the PN workforce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A survey was sent to the American Society of Pediatric Nephrology list of PN fellows (n = 103) in 2008. The 57 fellows (55%) who completed the survey were representative of the group. RESULTS: The majority decided on a career in PN as senior residents, most commonly due to their interest in renal physiology and academics. They felt residents chose other fields due to lack of interest/exposure to PN, financial constraints, and perceived PN workload. Fellows identified workload and their perception of faculty dissatisfaction as important concerns with PN. None of the respondents planned to leave fellowship, but 21% have considered this. Twenty-eight percent knew a PN fellow who resigned, thought to be due to workload, personal conflicts, and perceived faculty dissatisfaction. CONCLUSIONS: Exposing residents to PN earlier in training and emphasizing positive features may create greater interest in PN. PN programs should be cognizant of workload and the influence of faculty dissatisfaction. Ongoing evaluation of PN fellow perceptions can assist in efforts to enhance recruitment and retention.

At the bottom of the differential diagnosis list: unusual causes of pediatric hypertension.

Hypertension affects 1-5% of children and adolescents, and the incidence has been increasing in association with obesity. However, secondary causes of hypertension such as renal parenchymal diseases, congenital abnormalities and renovascular disorders still remain the leading cause of pediatric hypertension, particularly in children under 12 years old. Other less common causes of hypertension in children and adolescents, including immobilization, burns, illicit and prescription drugs, dietary supplements, genetic disorders, and tumors will be addressed in this review.

Single kidney and sports participation: perception versus reality.

OBJECTIVES: Physician opinions and practice patterns regarding the participation of children and adolescents with single, normal kidneys in contact/collision sports are widely varied. We hypothesize that limitation of participation from play based only on the presence of a single kidney is not supported by available data. We sought to determine recommendations of pediatric nephrologists regarding the participation of patients with single, normal kidneys in contact/collision sports and review the literature to determine the rate of sports-related kidney injury compared with other organs. METHODS: Members of the American Society of Pediatric Nephrology were surveyed regarding their recommendations for participation of patients with single, normal kidneys in contact/collision sports. Medical and sports literature databases were searched to determine sports-related kidney, brain, spinal cord, and cardiac injury rates and the sports associated with kidney injury. RESULTS: Sixty-two percent of respondents would not allow contact/collision sports participation. Eighty-six percent of respondents barred participation in American football, whereas only 5% barred cycling. Most cited traumatic loss of function as the reason for discouraging participation. The literature search found an incidence of catastrophic sports-related kidney injury of 0.4 per 1 million children per year from all sports. Cycling was the most common cause of sports-related kidney injury causing > 3 times the kidney injuries as football. American football alone accounted for 0.9 to 5.3 fatal brain injuries and 4.9 to 7.3 irreversible spinal cord injuries per 1 million players per year. Commotio cordis causes 2.1 to 9.2 deaths per year. CONCLUSIONS: Most pediatric nephrologists prohibit contact/collision sports participation by athletes with a single kidney, particularly football. The available evidence suggests that cycling is far more likely to cause kidney injury. In addition, kidney injury from sports is much less common than catastrophic brain, spinal cord, or cardiac injury. Restricting participation of patients with a single, normal kidney from contact/collision sports is unwarranted.

Unexplained acute renal failure in a toddler: a rare complication of Epstein-Barr virus.

A previously healthy toddler developed severe acute renal failure with nephromegaly and peripheral atypical lymphocytosis. Profound interstitial nephritis with acute tubular necrosis was diagnosed by renal biopsy, and both the clinical picture and serological evaluation suggested Epstein-Barr virus (EBV) as the etiological agent. The previous reports of EBV-induced renal failure and the clinical and pathological presentations of interstitial nephritis in children are reviewed.

Effects of AT(1A) receptor deletion on blood pressure and sodium excretion during altered dietary salt intake.

The present study was performed to investigate the role of type 1A ANG II (AT(1A)) receptors in regulating sodium balance and blood pressure maintenance during chronic dietary sodium variations in AT(1A) receptor-deficient (-/-) mice. Groups of AT(1A) (-/-) and wild-type mice were placed on a low (LS)-, normal (NS)-, or high-salt (HS) diet for 3 wk. AT(1A) (-/-) mice on an LS diet had high urinary volume and low blood pressure despite increased renin and aldosterone levels. On an HS diet, (-/-) mice demonstrated significant diuresis, yet blood pressure increased to levels greater than control littermates. There was no effect of dietary sodium intake on systolic blood pressures in wild-type animals. The pressure-natriuresis relationship in AT(1A) (-/-) mice demonstrated a shift to the left and a decreased slope compared with wild-type littermates. These studies demonstrate that mice lacking the AT(1A) receptor have blood pressures sensitive to changes in dietary sodium, marked alterations of the pressure-natriuresis relationship, and compensatory mechanisms capable of maintaining normal sodium balance across a wide range of sodium intakes.