Steroid-sensitive nephrotic syndrome (SSNS) accounts for .80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68310 26 (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and #589 controls; P=1.42310 217). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825310 25). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS.

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To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P[4.94E-20, odds ratio (OR) [1.90)

Multiple studies have documented racial differences in graft survival in kidney transplant recipients. Although several studies in adult kidney transplant recipients have evaluated risk factors that might predispose to these differences, studies in pediatric patients are lacking. This study retrospectively analyzed data from the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) to identify racial differences in kidney transplant outcomes and evaluate factors that might contribute to those differences. The study was restricted to the first NAPRTCS registry-reported kidney transplant for pediatric patients (age <21 yr) whose race was reported as either black or white. Univariate graft survival analyses were performed using the log rank statistic. Relative hazard rates for the effect of race on graft failure were determined using proportional hazards models. Multivariate analyses were restricted to patients with >30 d of graft survival and were adjusted for initial diagnosis, donor source, presence of delayed graft function, era of transplantation, estimated GFR at 30 d after transplantation, and number of days hospitalized in the first month after transplantation. Graft survival was significantly lower in black transplant recipients at 3 yr (70.9 versus 83.3%) and 5 yr (59.9 versus 77.7%). After controlling for confounding factors, black recipients continued to have a higher risk for graft failure than white recipients (adjusted hazard rate 1.65; 95% confidence interval 1.46 to 1.86). Significant racial differences in kidney transplant outcomes exist among pediatric patients even after controlling for confounding factors.

Hypertension is prevalent after renal transplantation (Tx) and associated with graft failure in children and adults. However, the effect of blood pressure (BP) on short-term renal allograft function is uncertain. We assessed the associations among BP pretransplant, and 3 months and 1 yr post-transplant, and 1-yr post-transplant measured glomerular filtration rate (mGFR) in 61 children with a functioning graft. The GFR was determined using a single intravenous (i.v.) injection of Optiray 350(R). Data were collected between January 1994 and January 2000. The mean mGFR 1 yr after renal transplant was 63.6 +/- 19.9 mL/min/1.73 m2 in 26 live donor recipients and 50.8 +/- 23.3 mL/min/1.73 m2 in 35 cadaveric donors (p = 0.029). Correlation analysis showed significant negative associations of 1-yr mGFR with systolic blood pressure (SBP) and diastolic blood pressure (DBP) 3 months after renal Tx (r = - 0.58, p < 0.0001 and r = - 0.50, p < 0.0001, respectively), and with SBP (r = - 0.37, p = 0.003) and DBP (r = - 0.32, p = 0.01) 1 yr after renal Tx. Multi-variate regression analysis showed that the SBP 3 months after Tx (p < 0.001), number of acute rejections (p = 0.002), donor age (p = 0.02), and cold ischemia time (p = 0.03) were independent predictors for the 1-yr mGFR. These results indicate that a higher SBP in the first few months post-renal Tx is associated with decreased renal allograft function in children 1 yr post-Tx.

Obesity is a major issue affecting health care delivery. While studies have been done in adults with end-stage renal disease, similar studies are lacking in pediatric patients with this disease. We retrospectively analyzed our renal transplant database from 1978 to 2002, to identify prevalence and predisposing factors to obesity in a pediatric end-stage renal disease population. Obesity, particularly in younger individuals, was found to be prevalent at transplantation.

A 6-yr-old boy developed progressively severe hypertension, which was unresponsive to medications, 1 week after percutaneous biopsy of his renal transplant. Renal angiogram revealed an arteriovenous fistula (AVF) in the lower pole at the site of the biopsy. Case findings and resolution after embolization are described, and the current literature is briefly reviewed.

Background In adults with chronic kidney disease (CKD), cigarette smoking is associated with an increased risk for CKD progression and transplant failure. In children, secondhand smoke (SHS) exposure has been associated with elevated blood pressure. There are no studies on the prevalence and effect of SHS exposure in CKD. Methods Subjects were enrolled in the Chronic Kidney Disease in Children (CKiD) Study, an observational cohort of 366 children aged 1 to 16 years with CKD. Secondhand smoke exposure was obtained via questionnaire. SHS exposure was also determined based on urine cotinine (Ucot) measurements (1 ng/mL≤Ucot<75 ng/mL). The cross-sectional association of SHS exposure with proteinuria was assessed. Results Using Ucot, 22 % of subjects were exposed to SHS. SHS exposure was significantly associated with lower maternal education and African American race, and a greater prevalence of nephrotic range proteinuria and left ventricular hypertrophy. In a multivariate model (including sex, age, race, maternal education, income level, private insurance status, abnormal birth history and CKD diagnosis), the prevalence odds of nephrotic range proteinuria was 2.64, (95 % confidence interval 1.08, 6.42) higher in children exposed to SHS compared to those unexposed. Conclusions In our cohort of children with CKD, SHS exposure was common (22 %) and independently associated with nephrotic range proteinuria. Exposure to SHS may be an important factor to consider in CKD progression.