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Cincinnati, OH, United States

Srivaths P.R.,Baylor College of Medicine | Goldstein S.L.,Section of Pediatric Nephrology | Krishnamurthy R.,Baylor College of Medicine | Silverstein D.M.,U.S. Food and Drug Administration
Pediatric Nephrology | Year: 2014

Background: Coronary calcifications (CC) portend increased mortality in adults receiving hemodialysis (HD), however the risk factors associated with CC progression are not well known in pediatric patients. Our previous cross-sectional studies demonstrated high CC prevalence (31 %) in pediatric patients, which were significantly associated with high serum phosphorus (P), fibroblast growth factor 23 (FGF) levels, dialysis vintage, and low cholesterol. The current study was undertaken to determine and elucidate CC progression in pediatric HD patients. Methods: A 1-year prospective longitudinal study of 16 pediatric patients (ten male; mean age, 16.9 ± 3 years; range, 10.1-20.4 years) receiving chronic HD was conducted. Results: CC were observed in five of 16 (31.3 %) patients on baseline computed tomogram (CT) scan; 14/16 patients underwent 1-year CT. All patients with initial CC who completed CT at 1 year (3/5) progressed; one patient had new CC and none of the patients had resolved CC. Mean Agatston score increased from 23.4 ± 18.06 HU (baseline) to 169 ± 298.9 HU. Patients with CC progression had higher mean serum P (8.6 ± 1.8 mg/dl vs. 6.3 ± 1.1 mg/dl, p = 0.015) and FGF 23 levels (3,994 ± 860.5 pg/ml vs. 2,327 ± 1,206.4 pg/ml, p = 0.028). Serum P and FGF 23 levels were positively correlated with final Agatston scores (R = 0.65, p = 0.01 for serum P and R = 0.54, p = 0.045 for FGF 23) and change in Agatston scores (R = 0.65, p = 0.01 for serum P and R = 0.52, p = 0.048 for FGF 23). Conclusions: Our study shows that CC is progressive in pediatric patients receiving HD and that increased serum P and FGF 23 levels are associated with this progression. © 2013 IPNA.


Atkinson M.A.,Johns Hopkins University | Martz K.,EMMES Corporation | Warady B.A.,Section of Pediatric Nephrology | Neu A.M.,Johns Hopkins University
Pediatric Nephrology | Year: 2010

Previous studies in children with chronic kidney disease (CKD) have identified low hemoglobin as a risk factor for poor outcomes. A retrospective review of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) CKD registry was performed to identify the prevalence of and risk factors for anemia among children with stage 3 CKD, including both patients with low hemoglobin and those whose hemoglobin normalized with an erythropoiesis-stimulating agent (ESA). At enrollment, 2,792 patients had stage 3 CKD. Mean age was 9.5 (±0.11) years, 62.1% were male, 61.3% were white, and 43.7% had structural/urologic disease. Among 1,640 of those patients with 12 month follow-up data available for multivariate analysis, 73% met the criteria for anemia. Multivariate logistic regression analysis identifying risk factors for anemia at the 12-month follow-up revealed that, after controlling for estimated glomerular filtration rate, age >2 years, male sex, earlier era of study entry, and prescription of anti-hypertensive medications are associated with an increased risk for anemia at 12 months. In addition, multivariate Cox proportional hazards regression analysis revealed that when patients with ESA-corrected hemoglobin are included in the definition, anemia is not associated with increased risk of progression to end stage renal disease (dialysis initiation or transplantation). © 2010 IPNA.


Seo-Mayer P.W.,Section of Pediatric Nephrology | Seo-Mayer P.W.,Yale University | Thulin G.,Yale University | Zhang L.,Yale University | And 5 more authors.
American Journal of Physiology - Renal Physiology | Year: 2011

Alterations in epithelial cell polarity and in the subcellular distributions of epithelial ion transport proteins are key molecular consequences of acute kidney injury and intracellular energy depletion. AMP-activated protein kinase (AMPK), a cellular energy sensor, is rapidly activated in response to renal ischemia, and we demonstrate that its activity is upregulated by energy depletion in Madin-Darby canine kidney (MDCK) cells. We hypothesized that AMPK activity may influence the maintenance or recovery of epithelial cell organization in mammalian renal epithelial cells subjected to energy depletion. MDCK cells were ATP depleted through a 1-h incubation with antimycin A and 2-deoxyglucose. Immunofluoresence localization demonstrated that this regimen induces mislocalization of the Na-K-ATPase from its normal residence at the basolateral plasma membrane to intracellular vesicular compartments. When cells were pretreated with the AMPK activator metformin before energy depletion, basolateral localization of Na-K-ATPase was preserved. In MDCK cells in which AMPK expression was stably knocked down with short hairpin RNA, preactivation of AMPK with metformin did not prevent Na-K-ATPase redistribution in response to energy depletion. In vivo studies demonstrate that metformin activated renal AMPK and that treatment with metformin before renal ischemia preserved cellular integrity, preserved Na-K-ATPase localization, and led to reduced levels of neutrophil gelatinase-associated lipocalin, a biomarker of tubular injury. Thus AMPK may play a role in preserving the functional integrity of epithelial plasma membrane domains in the face of energy depletion. Furthermore, pretreatment with an AMPK activator before ischemia may attenuate the severity of renal tubular injury in the context of acute kidney injury. © 2011 the American Physiological Society.


Mitsnefes M.M.,Cincinnati Childrens Hospital Medical Center | Pierce C.,Johns Hopkins University | Flynn J.,Seattle Childrens Hospital | Samuels J.,University of Houston | And 3 more authors.
Pediatric Nephrology | Year: 2016

Background: Studies in children with chronic kidney disease indicate a high prevalence of masked hypertension detected by ambulatory blood pressure monitoring (ABPM). However, it is not well known if the frequency of masked hypertension is related to the level of normal casual blood pressure (BP). Methods/Results: We hypothesized that lower levels of normal casual BP are associated with a lower prevalence of masked hypertension. Data from the chronic kidney disease (CKiD) cohort were analyzed cross-sectionally across multiple visits. The majority of children with normal casual BP also had normal wake and sleep ABP (60 %), even at the highest percentiles of casual BP. The frequency of masked hypertension was lower in children with casual BP ≤25th percentile versus those with casual BP in 26–50th percentile and casual BP in 51–90th percentile during both wake and sleep periods. In children with the lowest normal casual BP levels (≤25th percentile), the frequency of abnormal mean wake or sleep ABP was 2–7 %, and of abnormal BP load was 6–16 %. Conclusions: These data suggest that masked hypertension is unlikely if the casual BP is found to be in the low normal range. © 2015, IPNA.


Chen A.,Section of Pediatric Nephrology | Martz K.,EMMES Corporation | Rao P.S.,University of Michigan
Clinical Journal of the American Society of Nephrology | Year: 2012

Background and objectives Several adult studies report that patients returning to peritoneal dialysis after allograft failure have increased infection-related morbidity. The impact of allograft failure on infection risk in children is uncertain. We compared peritonitis-free survival between pediatric peritoneal dialysis patients with prior allograft failure and those who were transplant naive. Design, setting, participants, & measurements We studied patients, 2-21 years of age, who initiated peritoneal dialysis from January 1,1992, to December 31, 2007, in the North American Pediatric Renal Trials and Collaborative Studies registry. Demographic characteristics were compared between transplant naive and allograft failure patients using a chi-squared statistic. Peritonitis-free survival was compared between the two groups using Kaplan-Meier estimates. A Cox regression analysis was performed to adjust for covariates, which impact risk of peritonitis. Results Of 2829 patients on peritoneal dialysis, 445 had a prior history of allograft failure and 2384 did not (transplant naive). Demographic characteristics including age at dialysis initiation, race, primary renal disease, and era of dialysis initiation were significantly different between the two groups. Peritonitis-free survival was poorer for the allograft failure group. After covariate adjustment, allograft failure showed borderline significance as a factor predictive of peritonitis. Conclusions Children initiating peritoneal dialysis after allograft failure may experience a slightly higher infection risk. © 2012 by the American Society of Nephrology.

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