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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., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

The conduct of clinical trials in small pediatric subspecialties such as pediatric nephrology is hampered by both clinical demands on the pediatric nephrologist and the small number of appropriate patients available for such studies. The American Society of Pediatric Nephrology Therapeutics Development Committee (TDC) was established to (1) identify the various stakeholders with interests and/or expertise related to clinical trials in children with kidney disease and (2) develop more effective partnerships among all parties regarding strategies for successful clinical trial development and execution. This article discusses the rationale, structure, and function of the TDC, the status of progress toward its goals, and the insights gained to date that may be useful for other subspecialties that face similar challenges.

Nephrology has conducted few high-quality clinical trials, and the trials that have been conducted have not resulted in the approval of new treatments for primary or inflammatory glomerular diseases. There are overarching process issues that affect the conduct of all clinical trials, but there are also some specialty-specific issues. Within nephrology, primary glomerular diseases are rare, making adequate recruitment for meaningful trials difficult. Nephrologists need better ways, beyond histopathology, to phenotype patients with glomerular diseases and stratify the risk for progression to ESRD. Rigorous trial design is needed for the testing of new therapies, where most patients with glomerular diseases are offered the opportunity to enroll in a clinical trial if standard therapies have failed or are lacking. Training programs to develop a core group of kidney specialists with expertise in the design and implementation of clinical trials are also needed. Registries of patients with glomerular disease and observational studies can aid in the ability to determine realistic estimates of disease prevalence and inform trial design through a better understanding of the natural history of disease. Some proposed changes to the Common Rule, the federal regulations governing the ethical conduct of research involving humans, and the emerging use of electronic health records may facilitate the efficiency of initiating multicenter clinical trials. Collaborations among academia, government scientific and regulatory agencies, industry, foundations, and patient advocacy groups can accelerate therapeutic development for these complex diseases., (Copyright © 2016 by the American Society of Nephrology.)

Emerging evidence suggests an association between food sensitivity and gut microbiota in children with nephrotic syndrome. Diminished proteinuria resulted from eliminating cow's milk and the use of an oligoantigenic diet which excluded gluten, especially in patients with immune-related conditions, i.e., celiac disease and nephrotic syndrome. The mechanisms underlying the association of diet, gut microbiota, and dysregulation of the immune system are unknown. Gut microbiota is influenced by a number of factors including diet composition and other environmental epigenetic exposures. The imbalance in gut microbiota may be ameliorated by gluten-free and dairy-free diets. Gluten-free diet increased the number of unhealthy bacteria while reducing bacterial-induced cytokine production of IL-10. Thus, gluten-free diet may influence the composition and immune function of gut microbiota and should be considered a possible environmental factor associated with immune-related disease, including nephrotic syndrome. Furthermore, the imbalance of gut microbiota may be related to the development of cow's milk protein allergy. Investigations are needed to fill the gaps in our knowledge concerning the associations between the gut microbiome, environmental exposures, epigenetics, racial influences, and the propensity for immune dysregulation with its inherent risk to the developing individual.

Background and Objectives: Metabolic abnormalities and cardiovascular disease (CVD) risk factors have rarely been systematically assessed in children with chronic kidney disease (CKD). We examined the prevalence of various CKD sequelae across the GFR spectrum., Design, Setting, Participants, & Measurements: Data were used from 586 children participating in the Chronic Kidney Disease in Children (CKiD) study (United States and Canada) with GFR measured by iohexol plasma disappearance. Laboratory values and CVD risk factors were compared across GFR categories and with an age-, gender-, and race-matched community sample., Results: CKiD participants were 62% male, 66% Caucasian, 23% African American, and 15% Hispanic with a median age of 11 years and a median GFR of 44 ml/min per 1.73 m(2). Compared with those with a GFR ≥ 50 ml/min per 1.73 m(2), having a GFR < 30 ml/min per 1.73 m(2) was associated with a three-fold higher risk of acidosis and growth failure and a four- to five-fold higher risk of anemia and elevated potassium and phosphate. Median GFR change was -4.3 ml/min per 1.73 m(2) and -1.5 ml/min per 1.73 m(2) per year in children with glomerular and nonglomerular diagnoses, respectively. Despite medication and access to nephrology care, uncontrolled systolic hypertension was present in 14%, and 16% had left ventricular hypertrophy. Children with CKD frequently were also shorter and had lower birth weight, on average, compared with norms., Conclusions: Growth failure, metabolic abnormalities, and CVD risk factors are present at GFR >50 ml/min per 1.73 m(2) in children with CKD and, despite therapy, increase in prevalence two- to four-fold with decreasing GFR.

Background and Objectives: Poor linear growth is a well described complication of chronic kidney disease (CKD). This study evaluated whether abnormal birth history defined by low birth weight (LBW; <2500 g), prematurity (gestational age <36 weeks), small for gestational age (SGA; birth weight <10th percentile for gestational age), or intensive care unit (ICU) at birth were risk factors for poor growth outcomes in children with CKD., Design, Setting, Participants, & Measurements: Growth outcomes were quantified by age-sex-specific height and weight z-scores during 1393 visits from 426 participants of the Chronic Kidney Disease in Children Study, an observational cohort of children with CKD. Median baseline GFR was 42.9 ml/min per 1.73 m(2), 21% had a glomerular diagnosis, and 52% had CKD for ≥ 90% of their lifetime., Results: A high prevalence of LBW (17%), SGA (14%), prematurity (12%), and ICU after delivery (40%) was observed. Multivariate analyses demonstrated a negative effect of LBW (-0.43 ± 0.14; P < 0.01 for height and -0.37 ± 0.16; P = 0.02 for weight) and of SGA (-0.29 ± 0.16; P = 0.07 for height and -0.41 ± 0.19; P = 0.03 for weight) on current height and weight. In children with glomerular versus nonglomerular diagnoses, the effect of SGA (-1.08 versus -0.18; P = 0.029) on attained weight was more pronounced in children with a glomerular diagnosis., Conclusions: LBW and SGA are novel risk factors for short stature and lower weight percentiles in children with mild to moderate CKD independent of kidney function.

Purpose: Little is known about health related quality of life in adolescents with chronic kidney disease due to urological anomalies. We assessed generic health related quality of life in this population using a validated parent proxy instrument., Materials and Methods: In this multicenter prospective cohort study the Child Health Questionnaire-Parent Form 50, a generic health related quality of life parent proxy instrument, was administered to 92 parents of adolescents 10 to 18 years old with chronic kidney disease. Mean summary measure and scale scores in adolescents with urological anomalies were compared to scores in those with other causes of kidney disease and in a representative American population sample., Results: The cohort included 35 adolescents with an underlying diagnosis of congenital urological anomaly and 57 with another cause of kidney disease. There were no significant differences in mean scale or summary measure scores between the 2 diagnostic groups. When compared to a representative population sample, adolescents with congenital urological anomalies scored significantly worse on the questionnaire physical summary measure (44.5, 95% CI 39.9-49.1 vs 52.0, 95% CI 51.1-52.9, p = 0.002), and on the Child Health Questionnaire scales physical functioning, role physical, general health perceptions, family activities and parental emotional impact., Conclusions: As assessed by Child Health Questionnaire-Parent Form 50, parents reported that adolescents with chronic kidney disease due to urological disorders scored lower on the physical summary measure than a population based reference sample and they reported a negative effect on family activities and parental emotional well-being. These findings suggest that the Child Health Questionnaire-Parent Form 50 could provide a family based assessment of generic health related quality of life in adolescents with urological disorders.

Chronic kidney disease (CKD) in children is associated with dramatic changes in the growth hormone (GH) and insulin-like growth factor (IGF-1) axis, resulting in growth retardation. Moderate-to-severe growth retardation in CKD is associated with increased morbidity and mortality. Renal failure is a state of GH resistance and not GH deficiency. Some mechanisms of GH resistance are: reduced density of GH receptors in target organs, impaired GH-activated post-receptor Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and reduced levels of free IGF-1 due to increased inhibitory IGF-binding proteins (IGFBPs). Treatment with recombinant human growth hormone (rhGH) has been proven to be safe and efficacious in children with CKD. Even though rhGH has been shown to improve catch-up growth and to allow the child to achieve normal adult height, the final adult height is still significantly below the genetic target. Growth retardation may persist after renal transplantation due to multiple factors, such as steroid use, decreased renal function and an abnormal GH-IGF1 axis. Those below age 6 years are the ones to benefit most from transplantation in demonstrating acceleration in linear growth. Newer treatment modalities targeting the GH resistance with recombinant human IGF-1 (rhIGF-1), recombinant human IGFBP3 (rhIGFBP3) and IGFBP displacers are under investigation and may prove to be more effective in treating growth failure in CKD.

Malnutrition is a serious complication of chronic kidney disease (CKD) in the pediatric population. Management of the nutritional status of children presents the challenge of ensuring sufficient energy to promote linear growth, development of brain and organs, and maintenance of appropriate fat and muscle stores, while preventing excess protein intake and controlling electrolytes. Aggressive nutrition intervention in the early stages of CKD may be critical in the prevention of more serious complications further in the disease process. Nutrition assessment involves analysis of dietary intake, anthropometric parameters, and laboratory data. Currently, no guidelines are available for nutritional management of pediatric patients with CKD before the onset of dialysis. The content and algorithms in this article are intended to serve as a guide in the management of the nutritional status of children with CKD. Although adequate calorie and protein intake is critical in prevention of malnutrition, it is only part of a complex mechanism in the development of cachexia in CKD. Research suggests that the effects of inflammatory cytokines and hormones such as leptin and ghrelin play a role in the development of malnutrition in CKD. As a more thorough understanding of this mechanism emerges, new treatments aimed at inhibiting cachexia can be developed.

We sought to describe rates of kidney function decline and to identify modifiable risk factors for CKD progression in a multicenter prospective cohort study of adolescents with CKD aged 11 to 18 years seen semiannually for up to three years. Of the 23 subjects meeting inclusion criteria, the average estimated GFR was 51 +/- 27 ml/min/1.73 m(2) (0.85 +/- 0.45 ml/s/1.73 m(2)) at entry. The overall annualized decline in GFR was 5.6 ml/min/1.73 m(2) (0.093 ml/s/1.73 m(2)) per year (95% confidence interval [95% CI]: 1.9 to 9.3 [0.032 to 0.16]). The adjusted annualized decline in GFR was found to be accelerated in males, as well as among those over 15 years of age. The adjusted annualized decline in GFR was greater among those with either anemia (hematocrit below 36%), or hypoalbuminemia (albumin below 4 g/dl [40 g/L]). After adjustment, anemia was associated with an accelerated decline of 7.8 ml/min/1.73 m(2) (0.13 ml/s/1.73 m(2)) (95% CI: 3.3 to 12 [0.055 to 0.20]) and hypoalbuminemia was associated with an accelerated decline of 17 ml/min/1.73 m(2) (0.28 ml/s/1.73 m(2)) (95% CI: 11 to 22 [0.18 to 0.37]). Further study is needed to evaluate whether treatment of anemia or hypoalbuminemia, as outlined in current clinical care guidelines for CKD, may slow the progression of CKD in adolescents.

An estimated 650,000 Americans will have ESRD by 2010. Young adults with kidney failure often develop progressive chronic kidney disease (CKD) in childhood and adolescence. The Chronic Kidney Disease in Children (CKiD) prospective cohort study of 540 children aged 1 to 16 yr and have estimated GFR between 30 and 75 ml/min per 1.73 m2 was established to identify novel risk factors for CKD progression; the impact of kidney function decline on growth, cognition, and behavior; and the evolution of cardiovascular disease risk factors. Annually, a physical examination documenting height, weight, Tanner stage, and standardized BP is conducted, and cognitive function, quality of life, nutritional, and behavioral questionnaires are completed by the parent or the child. Samples of serum, plasma, urine, hair, and fingernail clippings are stored in biosamples and genetics repositories. GFR is measured annually for 2 yr, then every other year using iohexol, HPLC creatinine, and cystatin C. Using age, gender, and serial measurements of Tanner stage, height, and creatinine, compared with iohexol GFR, a formula to estimate GFR that will improve on traditional pediatric GFR estimating equations when applied longitudinally is expected to be developed. Every other year, echocardiography and ambulatory BP monitoring will assess risk for cardiovascular disease. The primary outcome is the rate of decline of GFR. The CKiD study will be the largest North American multicenter study of pediatric CKD.

Carnitine is an amino acid derivative that has a key role in the regulation of fatty acid metabolism and ATP formation. Carnitine deficiency has been described in various conditions, including chronic kidney disease (CKD) and end stage renal disease (ESRD). The deficiency of this micronutrient is postulated to lead to adverse effects across multiple organ systems. There is a paucity of information on carnitine deficiency and its effects in the pediatric CKD and ESRD populations. Currently, there is no evidence supporting the routine use of carnitine supplementation in children with ESRD. In this article, we review the pathophysiology, pharmacokinetics and the potential effects of levo-carnitine supplementation with a focus on the pediatric CKD and ESRD populations. Finally, potential future directions of research are discussed.

Growth retardation is a common complication in children with chronic kidney disease. Treatable causes of growth retardation in these patients include renal osteodystrophy, metabolic acidosis, and inadequate nutritional intake. In addition, disturbances in the growth hormone-insulinlike growth factor I axis are a major cause of decreased growth. Administration of recombinant human growth hormone can overcome this problem, allowing catch-up growth and achievement of normal or improved adult height.

Background: Acute renal failure from ischemia/reperfusion injury is associated with tubule cell apoptosis, the molecular mechanisms of which remain under active investigation. The purpose of this study was to identify apoptosis-related genes that are differentially expressed in the early periods following renal ischemia., Methods: Mice underwent unilateral renal artery clamping for 45 minutes and were sacrificed at 0, 3, 12, or 24 hours of reperfusion. Tubule cell apoptosis was confirmed by DNA laddering and terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick end labeling (TUNEL) assay. We employed cDNA microarrays to define global changes in renal gene expression. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used as confirmatory tools., Results: By microarray analysis, we identified consistent patterns of altered gene expression, including transcription factors, growth factors, signal transduction molecules, and apoptotic factors. Prominent among the last category included FADD, DAXX, BAD, BAK, and p53. Up-regulation of these proapoptotic genes was confirmed by semiquantitative RT-PCR and immunohistochemistry., Conclusion: The results indicate that apoptosis may represent an important mechanism for the early loss of tubule cells following ischemia/reperfusion injury. Both the death receptor-dependent (FADD-DAXX) and mitochondrial (BAD-BAK) pathways are activated. The results also provide a molecular basis for the previous findings that significant intrarenal mechanisms exist to enable tubule cell repair and regeneration, as evidenced by the up-regulation of genes such as growth, proliferation, transcription, and cytoskeletal factors.

Background: Hyponatremia is a common electrolyte disorder and a prognostic marker for mortality. We hypothesize that in advanced chronic or acute kidney disease, hyponatremia is not independently associated with mortality because of the contribution of kidney failure to its pathophysiology.Methods: Clinical Looking Glass, Montefiore’s clinical database, was used to build a cohort of all patients hospitalized between January of 2009 and December of 2011. A chronic kidney disease (CKD) group and an acute kidney injury (AKI) group were defined based on GFR measurements during and before index hospitalization. Cox regression models assessed the hazard for death for those with community acquired hyponatremia as compared to those without hyponatremia, stratified by stage of kidney disease within each cohort.Results: Forty-four thousand four hundred and seventy-six patients were studied. Forty six percent (46.2%) of subjects were in the CKD cohort and 53.8% were in the AKI cohort. Hyponatremic patients were older, and had a higher prevalence of CKD and AKI. A total of 7,934 subjects died (17.8%) during 22 months of follow-up. In CKD and AKI cohorts, hyponatremia, age, race, illness severity and Charlson score were associated with mortality. Hyponatremia had similar hazard ratios (HR) across kidney disease stages despite loss of statistical significance in later stages due to smaller sample size.Conclusions: The association between community acquired hyponatremia and mortality showed consistent HRs across progressive stages of CKD and AKI suggesting that the contribution of tubular dysfunction to hyponatremia in advanced kidney disease does not alter this association. [ABSTRACT FROM AUTHOR]

Background: Individuals of African ancestry harboring two variant alleles within apolipoprotein L1 (APOL1) are classified with a high-risk (HR) genotype. Adults with an HR genotype have increased risk of focal segmental glomerulosclerosis and chronic kidney disease compared with those with a low-risk (LR) genotype (0 or 1 variants). The role of APOL1 risk genotypes in children with glomerular disease is less well known. Methods: This study characterized 104 African-American children with a glomerular disease by APOL1 genotype in two cohorts: the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE).Results: Among these subjects, 46% had an HR genotype with a similar age at cohort enrollment. For APOL1 HR children, the median age of disease onset was older (CKiD: 4.5 versus 11.5 years for LR versus HR; NEPTUNE: 11 versus 14 years for LR versus HR, respectively) and preterm birth was more common [CKiD: 27 versus 4%; NEPTUNE: 26 versus 12%; combined odds ratio 4.6 (95% confidence interval: 1.4, 15.5)]. Within studies, HR children had lower initial estimated glomerular filtration rate (eGFR) (CKiD: 53 versus 69 mL/min/1.73 m2; NEPTUNE: 74 versus 94 mL/min/1.73 m2). Longitudinal eGFR decline was faster among HR children versus LR (CKiD: −18 versus −8% per year; NEPTUNE: −13 versus −3% per year). Conclusions: Children with an HR genotype in CKiD and NEPTUNE seem to have a more aggressive form of glomerular disease, in part due to a higher prevalence of focal segmental glomerulosclerosis. These consistent findings across independent cohorts suggest a common natural history for children with APOL1-associated glomerular disease. Further study is needed to determine the generalizability of these findings. [ABSTRACT FROM AUTHOR]

Background: Despite recent advances in chronic kidney disease (CKD) and end-stage renal disease (ESRD) management, morbidity and mortality in this population remain exceptionally high. Persistent, low-grade inflammation has been recognized as an important component of CKD, playing a unique role in its pathophysiology and being accountable in part for cardiovascular and all-cause mortality, as well as contributing to the development of protein-energy wasting. Summary: The variety of factors contribute to chronic inflammatory status in CKD, including increased production and decreased clearance of pro-inflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, including those related to dialysis access, altered metabolism of adipose tissue, and intestinal dysbiosis. Inflammation directly correlates with the glomerular filtration rate (GFR) in CKD and culminates in dialysis patients, where extracorporeal factors, such as impurities in dialysis water, microbiological quality of the dialysate, and bioincompatible factors in the dialysis circuit play an additional role. Genetic and epigenetic influences contributing to inflammatory activation in CKD are currently being intensively investigated. A number of interventions have been proposed to target inflammation in CKD, including lifestyle modifications, pharmacological agents, and optimization of dialysis. Importantly, some of these therapies have been recently tested in randomized controlled trials. Key Messages: Chronic inflammation should be regarded as a common comorbid condition in CKD and especially in dialysis patients. A number of interventions have been proven to be safe and effective in well-designed clinical studies. This includes such inexpensive approaches as modification of physical activity and dietary supplementation. Further investigations are needed to evaluate the effects of these interventions on hard outcomes, as well as to better understand the role of inflammation in selected CKD populations (e.g., in children). © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

We describe the experience of the focal segmental glomerulosclerosis clinical trial (FSGS CT) in the identification and recruitment of participants into the study. This National Institutes of Health funded study, a multicenter, open-label, randomized comparison of cyclosporine versus oral dexamethasone pulses plus mycophenolate mofetil, experienced difficulty and delays meeting enrollment goals. These problems occurred despite the support of patient advocacy groups and aggressive recruitment strategies. Multiple barriers were identified including: (1) inaccurate estimates of the number of potential incident FSGS patients at participating centers; (2) delays in securing one of the test agents; (3) prolonged time between IRB approval and execution of a subcontract (mean 7.5 ± 0.8 months); (4) prolonged time between IRB approval and enrollment of the first patient at participating sites (mean 19.6 ± 1.4 months); and (5) reorganization of clinical coordinating core infrastructure to align resources with enrollment. A Web-based anonymous survey of site investigators revealed site-related barriers to patient recruitment. The value of a variety of recruitment tools was of marginal utility in facilitating patient enrollment. We conclude that improvements in the logistics of study approval and regulatory start-up and testing of promising novel agents are important factors in promoting enrollment into randomized clinical trials in nephrology. Clin Trans Sci 2013; Volume 6: 13-20 [ABSTRACT FROM AUTHOR]

The article provides information on focal segmental glomerulosclerosis, which accounts for almost 20 percent of cases of the nephrotic syndrome in children and 40 percent of such cases in adults. It says that the condition is the most common primary glomerular disorder causing end-stage renal disease in the U.S. The author adds that proteinuria is a defining feature accompanied by peripheral edema, hypercholesterolemia and hypoalbuminemia. The pathogenesis of the condition is also discussed.

Malformations of the kidney and lower urinary tract are the most frequent cause of end-stage renal disease in children. Mutations in HNF1Β and PAX2 commonly cause syndromic urinary tract malformation. We searched for mutations in HNF1Β and PAX2 in North American children with renal aplasia and hypodysplasia (RHD) enrolled in the Chronic Kidney Disease in Children Cohort Study (CKiD). We identified seven mutations in this multiethnic cohort (10% of patients). In HNF1Β, we identified a nonsense (p.R181X), a missense (p.S148L), and a frameshift (Y352fsX352) mutation, and one whole gene deletion. In PAX2, we identified one splice site (IVS4-1G>T), one missense (p.G24E), and one frameshift (G24fsX28) mutation. All mutations occurred in Caucasians, accounting for 14% of disease in this subgroup. The absence of mutations in other ethnicities is likely due to the limited sample size. There were no differences in clinical parameters (age, baseline eGFR, blood pressure, body mass index, progression) between patients with or without HNF1B and PAX2 mutations. A significant proportion of North American Caucasian patients with RHD carry mutations in HNF1Β or PAX2 genes. These patients should be evaluated for complications (e.g., diabetes for HNF1Β mutations, colobomas for PAX2) and referred for genetic counseling. [ABSTRACT FROM AUTHOR]

Purpose: We examined health related quality of life in adolescents with congenital urological disease causing kidney disease using a generic health related quality of life instrument. We then compared the results to those in adolescents with medical kidney disease and to population based norms. Materials and Methods: The Child Health and Illness Profile-Adolescent Edition was administered to 113 patients 10 to 18 years old with chronic kidney disease. Mean domain and subdomain scores for adolescents with urological disease were compared to those of adolescents with medical kidney disease and to population based norms. Results: The cohort included adolescents with an underlying diagnosis of congenital urological anomaly (37 patients) or other causes of kidney disease (76). Compared to adolescents with kidney disease caused by other factors, those with congenital urological disease scored statistically significantly better in the Child Health and Illness Profile-Adolescent Edition subdomain of Limitations of Activity (mean 22.3 [SD 2.5] vs 20.4 [SD 5.0], p = 0.04). Compared to population norms, adolescents with congenital disorders scored lower in the Disorders domain (mean 16.5, 95% CI 14.2 to 18.9) but better in the Risks domain (mean 25.9, 95% CI 25.1 to 26.6) and in the Home Safety and Health subdomain (mean 25.2, 95% CI 23.7 to 26.6). Conclusions: As assessed by the Child Health and Illness Profile-Adolescent Edition generic health status questionnaire, adolescents with kidney disease due to underlying congenital urological disease had fewer limitations of activity compared to those with underlying medical kidney disease. Except for low scores in the Disorders domain, children with underlying urological disease did not have significant impairments in any other domain compared to population based norms. [Copyright &y& Elsevier]

Focal segmental glomerulosclerosis (FSGS) is a major cause of idiopathic steroid-resistant nephrotic syndrome (SRNS) and end-stage kidney disease (ESKD). In recent years, animal models and studies of familial forms of nephrotic syndrome helped elucidate some mechanisms of podocyte injury and disease progression in FSGS. This article reviews some of the experimental and clinical data on the pathophysiology of FSGS. [ABSTRACT FROM AUTHOR]

The response to steroid therapy is used to characterize the idiopathic nephrotic syndrome (INS) of childhood as either steroid-sensitive (SSNS) or steroid-resistant (SRNS), a classification with a better prognostic capability than renal biopsy. The majority (∼80%) of INS is due to minimal change disease but the percentage of focal and segmental glomerulosclerosis is increasing. We applied a new technological platform to examine the urine proteome to determine if different urinary protein excretion profiles could differentiate patients with SSNS from those with SRNS. Twenty-five patients with INS and 17 control patients were studied. Mid-stream urines were analyzed using surface enhanced laser desorption and ionization mass spectrometry(SELDI-MS). Data were analyzed using multiple bioinformatic techniques. Patient classification was performed using Biomarker Pattern SoftwareTM and a generalized form of Adaboost and predictive models were generated using a supervised algorithm with cross-validation. Urinary proteomic data distinguished INS patients from control patients, irrespective of steroid response, with a sensitivity of 92.3%, specificity of 93.7%, positive predictive value of 96% and a negative predictive value of 88.2%. Classification of patients as SSNS or SRNS was 100%. A protein of mass 4,144 daltons was identified as the single most important classifier in distinguishing SSNS from SRNS. SELDI-MS combined with bioinformatics can identify different proteomic patterns in INS. Characterization of the proteins of interest identified by this proteomic approach with prospective clinical validation may yield a valuable clinical tool for the non-invasive prediction of treatment response and prognosis. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The Brenner hypothesis postulated that low birth weight and decreased nephron number at birth are linked to chronic kidney disease and systemic hypertension in adulthood. To date, little is known about the effect of extrauterine growth retardation (EUGR) on adult kidney disease. Bacchetta et al. present novel data using inulin to show a decrease in renal function for premature children with EUGR. The role of protein nutrition and timing in nephrogenesis is discussed.Kidney International (2009) 76, 361–363. doi:10.1038/ki.2009.181 [ABSTRACT FROM AUTHOR]

The article presents the consensus reached at first NIH/Office of Rare Diseases Conference on cystinosis, which was held on May 12-13, 2004. The meeting addressed the past, present, and future of nephropathic cystinosis research. In this meeting there was agreement on the importance of several topics related to the disease like early diagnosis of cystinosis, efficiency of treatment, oral cysteamine therapy, role of pediatric nephrologists, etc. It was finally concluded that future studies should include investigations into the value of therapies to reduce proteinuria.

Information about the 8th Symposium on Growth and Nutrition in Children with Chronic Renal Disease held in May 2009 are presented. Topics discussed include growth hormone and insulin-like growth factor 1 (IGF-1) physiology; growth plate metabolism; and bone cell biology.

The article focuses on a study on the association between the early diagnosis of primary hyperoxaluria type 1 (PH1) in children and good renal outcome. PH1 is defined as an autosomal-recessive disorder that is characterized by oxaluria and leads to early nephrocalcinosis and subsequent nephrolithiasis. It stresses the need to make every effort to diagnose patients with PH1 before they become symptomatic, and to examine the siblings of affected patients. It notes that neonatal screening is the only way to guarantee the earliest diagnosis of PH1.

The article presents the proceedings of the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth. Children with chronic renal failure (CRF) fail to attain adult height consistent with their genetic potential. The profound growth failure is multifactorial; major contributing factors include accumulation of uremic toxins and inhibitors of hormone action, renal osteodystrophy, and metabolic acidosis, malnutrition and drug toxicity, particularly of glucocorticoids. The Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease, "The Molecular Basis of Skeletal Growth", by the International Pediatric Nephrology Association (IPNA) continued a tradition that was initiated in 1977 and led to regular scientific symposia every three to five years.

Optimal therapy of patients with steroid-resistant primary focal segmental glomerulosclerosis (FSGS) remains controversial. This report describes the initial study design, baseline characteristics, and quality of life of patients enrolled in the FSGS Clinical Trial, a large multicenter randomized study of this glomerulopathy comparing a 12-month regimen of cyclosporine to the combination of mycophenolate mofetil and oral dexamethasone. Patients with age ranging 2-40 years, with an estimated glomerular filtration rate >40 ml/min per 1.73 m2, a first morning urine protein-to-creatinine ratio over one, and resistant to corticosteroids were eligible. The primary outcome was complete or partial remission of proteinuria over 52 weeks after randomization. In all, 192 patients were screened, of whom 138 were randomized for treatment. Ethnic distributions were 53 black, 78 white, and 7 other. By self- or parent-proxy reporting, 26 of the 138 patients were identified as Hispanic. The baseline glomerular filtration rate was 112.4 (76.5, 180.0) ml/min per 1.73 m2, and urine protein was 4.0 (2.1, 5.3) g/g. Overall, the quality of life of the patients with FSGS was lower than healthy controls and similar to that of patients with end-stage renal disease. Thus, the impact of FSGS on quality of life is significant and this measurement should be included in all trials. [ABSTRACT FROM AUTHOR]

BACKGROUND. There is frequent uncertainty in the identification of specific etiologies of chronic kidney disease (CKD) in children. Recent studies indicate that chromosomal microarrays can identify rare genomic imbalances that can clarify the etiology of neurodevelopmental and cardiac disorders in children; however, the contribution of unsuspected genomic imbalance to the incidence of pediatric CKD is unknown. METHODS. We performed chromosomal microarrays to detect genomic imbalances in children enrolled in the Chronic Kidney Disease in Children (CKiD) prospective cohort study, a longitudinal prospective multiethnic observational study of North American children with mild to moderate CKD. Patients with clinically detectable syndromic disease were excluded from evaluation. We compared 419 unrelated children enrolled in CKiD to multiethnic cohorts of 21,575 children and adults that had undergone microarray genotyping for studies unrelated to CKD. RESULTS. We identified diagnostic copy number disorders in 31 children with CKD (7.4% of the cohort). We detected 10 known pathogenic genomic disorders, including the 17q12 deletion HNF1 homeoboxB (HNF1B) and triple X syndromes in 19 of 419 unrelated CKiD cases as compared with 98 of 21,575 control individuals (OR 10.8, P = 6.1 x 10-20). In an additional 12 CKiD cases, we identified 12 likely pathogenic genomic imbalances that would be considered reportable in a clinical setting. These genomic imbalances were evenly distributed among patients diagnosed with congenital and noncongenital forms of CKD. In the vast majority of these cases, the genomic lesion was unsuspected based on the clinical assessment and either reclassified the disease or provided information that might have triggered additional clinical care, such as evaluation for metabolic or neuropsychiatric disease. CONCLUSION. A substantial proportion of children with CKD have an unsuspected genomic imbalance, suggesting genomic disorders as a risk factor for common forms of pediatric nephropathy. Detection of pathogenic imbalances has practical implications for personalized diagnosis and health monitoring in this population. TRIAL REGISTRATION. ClinicalTrials.gov NCT00327860. FUNDING. This work was supported by the NIH, the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute. [ABSTRACT FROM AUTHOR]

The article presents the case study of a 4-year old boy found to be suffering from proteinuria during routine examination. Symmetric corneal crystals were revealed by slit-lamp examination and the child was treated for cystinosis. The case shows that multinucleated podocytes should suggest the possibility of nephropathic cystinosis, even if Fanconi syndrome or chronic tubulo-interstitial nephropathy is not history of the diseases.