Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children

PubMedID: 31005273Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6–17 years with baseline estimated glomerular filtration rate (eGFR) of 10–60 ml/min/1.73 m2. uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m2, and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m2, or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69–0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD. © 2019 International Society of Nephrology2012-305608 Seventh Framework Programme 01EO0802Support for the 4C Study was received from the ERA-EDTA Research Programme, the KfH Foundation for Preventive Medicine, and the German Federal Ministry of Education and Research (reference number: 01EO0802). FS and MK received support for this study from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 2012-305608 (EURenOmics). FS, EW, FL, EV, and AM are members of the European Reference Network for Rare Kidney Diseases (ERKNet)

Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease

PubMedID: 31428929Background: Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients. Methods: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6–17 years with initial eGFR of 10–60 ml/min per 1.73 m2. Results: The median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 µmol/l (8.7) and 17.0 µmol/l (21.6), respectively. In a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors. Conclusions: Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort. © 2019, IPNA.01EO0802This study was made possible by grants from the European Renal Association-European Dialysis and Transplant Association ( www.era-edta.org ), the Kuratorium für Dialyse und Nierentransplantation (KfH) Foundation for Preventive Medicine, the German Federal Ministry of Education and Research (reference no. 01EO0802), and Pfizer Deutschland GmbH. The entire study was solely initiated and performed by the investigators of the 4C study group. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

Discontinuation of RAAS inhibition in children with advanced

PubMed: 322532752-s2.0-85084379982Background and objectives Although renin-angiotensin-aldosterone system inhibition (RAASi) is a cornerstone in the treatment of children with CKD, it is sometimes discontinued when kidney function declines. We studied the reasons of RAASi discontinuation and associations between RAASi discontinuation and important risk markers of CKD progression and on eGFR decline in the Cardiovascular Comorbidity in Children with CKD study. Design, setting, participants, & measurements In this study, 69 children with CKD(67% male, mean age 13.7 years, mean eGFR 27 ml/min per 1.73 m2) who discontinued RAASi during prospective follow-upwere included. Initial change in BP, albuminuria, and potassium after discontinuation were assessed (median time 6 months). Rate of eGFR decline (eGFR slope) during amedian of 1.9 years before and 1.2 years after discontinuation were estimated using linear mixed effects modeling. Results Physician-reported reasons for RAASi discontinuation were increase in serum creatinine, hyperkalemia, and symptomatic hypotension. After discontinuation of RAASi, BP and albuminuria increased, whereas potassium decreased. eGFR declinedmore rapidly after discontinuation of RAASi (-3.9ml/min per 1.73m2 per year; 95%confidence interval, -5.1 to -2.6) compared with the slope during RAASi treatment (-1.5 ml/min per 1.73 m2 per year; 95% confidence interval, -2.4 to -0.6; P=0.005). In contrast, no change in eGFR slope was observed in a matched control cohort of patients in whom RAASi was continued. Conclusions Discontinuation of RAASi in children with CKD is associated with an acceleration of kidney function decline, even in advanced CKD. © 2020 by the American Society of Nephrology.EO0802 National Institute for Health Research, NIHR Bundesministerium für Bildung und Forschung, BMBF: 01EO0802Support for the 4C Study was received from the European Renal Association-European Dialysis and Transplant Association Research Programme, the Kuratorium für Heimdialyse Foundation for Preventive Medicine and the German Federal Ministry of Education andResearch(referencenumber:01EO0802).Dr.Schaefer,Dr.Wühl, Dr. Bacchetta, Mr. Azukaitis, Dr. Melk, and Dr. Shroff are members of the European Reference Network for Rare Kidney Diseases (ERKNet). Dr. Shroff is supported by a National Institute for Health Research Career Development Fellowship.Support for the 4C Study was received from the European Renal Association-European Dialysis and Transplant Association Research Programme, the Kuratorium f?r Heimdialyse Foundation for Preventive Medicine and the German Federal Ministry of Education and Research (referencenumber: 01EO0802). Dr. Schaefer, Dr. W?hl, Dr. Bacchetta, Mr. Azukaitis, Dr. Melk, and Dr. Shroff are members of the European Reference Network for Rare Kidney Diseases (ERKNet). Dr. Shroff is supported by a National Institute for Health Research Career Development Fellowship

LONGITUDINAL EVALUATION OF CARDIOVASCULAR RISK AFTER PEDIATRIC KIDNEY TRANSPLANTATION

WOS: 000440358700043PubMed ID: 2610274

LONGITUDINAL FOLLOW-UP OF CARDIOVASCULAR COMORBIDITY IN PEDIATRIC RENAL TRANSPLANT RECIPIENTS - RESULTS FROM THE 4C-T STUDY

WOS: 00035163320024