Gina Marie Barletta

High Prevalence of the Metabolic Syndrome and Associated Left Ventricular Hypertrophy in Pediatric Renal Transplant Recipients

Wilson AC, Greenbaum LA, Barletta GM, Chand D, Lin J‐J, Patel HP, Mitsnefes M. High prevalence of the metabolic syndrome and associated left ventricular hypertrophy in pediatric renal transplant recipients.
Pediatr Transplantation 2010: 14: 52–60© 2009 John Wiley & Sons A/S.

HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome

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=1.68×10(-6) (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=1.42×10(-17)). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825×10(-5)). 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.

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.

Hemoglobin Differences by Race in Children With CKD

BACKGROUND There are known racial disparities in the prevalence of anemia in adults with chronic kidney disease (CKD), but these differences have not been well described in children. STUDY DESIGN Cohort study, cross-sectional analysis. SETTING & PARTICIPANTS The Chronic Kidney Disease in Children (CKiD) Study is a multicenter prospective cohort study of children with mild to moderate CKD. This analysis included 429 children of African American or white race. PREDICTOR Race. OUTCOMES & MEASUREMENTS This study examined the association of race with hemoglobin level. Both multiple linear regression and generalized gamma modeling techniques were used to characterize the association between race and hemoglobin level. RESULTS 79% of the cohort was white, 21% was African American. Neither median hemoglobin level nor frequency of erythropoiesis-stimulating agent use differed by race. In multivariate analysis, lower levels of iohexol-measured glomerular filtration rate, African American race, and glomerular disease (vs nonglomerular disease) as the underlying cause of CKD were independently associated with decreased hemoglobin levels; independent of glomerular filtration rate and CKD diagnosis, African American children had average hemoglobin levels that were 0.6 g/dL (95% CI, -0.9 to -0.2 g/dL) lower than those of white children. Generalized gamma modeling showed that differences in hemoglobin levels observed by race become more pronounced when moving from high to low in the overall hemoglobin level distribution. LIMITATIONS Cross-sectional analysis cannot establish causality, and data for iron stores were not available for all patients. CONCLUSIONS African American compared with white children have lower hemoglobin values in CKD independent of the underlying cause of CKD. These racial differences in hemoglobin levels appear to increase at the lower end of the hemoglobin level distribution in this population.

Is Blood Pressure Improving in Children With Chronic Kidney Disease?: A Period Analysis

Uncontrolled hypertension in children with chronic kidney disease (CKD) has been identified as one of the main factors contributing to progression of CKD and increased risk for cardiovascular disease. Recent efforts to achieve better blood pressure (BP) control have been recommended. The primary objective of this analysis was to compare BP control over 2 time periods among participants enrolled in the CKiD study (Chronic Kidney Disease in Children). Casual BP and 24-hour ambulatory BP monitor data were compared among 851 participants during 2 time periods: January 1, 2005, through July 1, 2008 (period 1, n=345), and July 1, 2010, through December 31, 2013 (period 2, n=506). Multivariable logistic regression to model the propensity of a visit record being in period 2 as a function of specific predictors was performed. After controlling for confounding variables (age, sex, race, socioeconomics, CKD duration, glomerular filtration rate, proteinuria, body mass index, growth failure, and antihypertensives), no significant differences were detected between time periods with respect to casual BP status (prehypertension: 15% versus 15%; uncontrolled hypertension: 18% versus 17%; P=0.87). Analysis of ambulatory BP monitor data demonstrated higher ambulatory BP indices, most notably masked hypertension in period 2 (36% versus 49%; P<0.001). Average sleep BP index (P<0.05) and sleep BP loads (P<0.05) were higher in period 2. Despite publication of hypertension recommendations and guidelines for BP control in patients with CKD, this study suggests that hypertension remains undertreated and under-recognized in children with CKD. This analysis also underscores the importance of routine ambulatory BP monitor assessment in children with CKD.

Mycophenolate mofetil-related leukopenia in children and young adults following kidney transplantation: Influence of genes and drugs.

MMF is commonly prescribed following kidney transplantation, yet its use is complicated by leukopenia. Understanding the genetics mediating this risk will help clinicians administer MMF safely. We evaluated 284 patients under 21 years of age for incidence and time course of MMF‐related leukopenia and performed a candidate gene association study comparing the frequency of 26 SNPs between cases with MMF‐related leukopenia and controls. We matched cases by induction, steroid duration, race, center, and age. We also evaluated the impact of induction and SNPs on time to leukopenia in all cases. Sixty‐eight (24%) patients had MMF‐related leukopenia, of which 59 consented for genotyping and 38 were matched with controls. Among matched pairs, no SNPs were associated with leukopenia. With non‐depleting induction, UGT2B7‐900A>G (rs7438135) was associated with increased risk of MMF‐related leukopenia (P = .038). Time to leukopenia did not differ between patients by induction agent, but 2 SNPs (rs2228075, rs2278294) in IMPDH1 were associated with increased time to leukopenia. MMF‐related leukopenia is common after transplantation. UGT2B7 may influence leukopenia risk especially in patients without lymphocyte‐depleting induction. IMPDH1 may influence time course of leukopenia after transplant.