@article{b31a2749ddff4c28b336c6964146c74a,
title = "Plasma Soluble Urokinase Plasminogen Activator Receptor (suPAR) and CKD Progression in Children",
abstract = "Rationale & Objective: Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker associated with incident chronic kidney disease (CKD) and has been identified as an independent risk factor for CKD progression in children, although these findings remain preliminary, limited to a single point in time, and unreplicated in pediatric cohorts. Study Design: Prospective longitudinal cohort study. Setting & Participants: 565 participants aged 1 to 16 years enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Exposure: Plasma suPAR levels, categorized by quartiles, measured at study entry and a 6-month follow-up interval. Outcome: CKD progression, defined as the initiation of kidney replacement therapy (dialysis or transplantation) or >50% decline in estimated glomerular filtrate rate (eGFR). Analytic Approach: Associations between plasma suPAR quartiles and risk for CKD progression were estimated using lognormal survival models, adjusting for potential confounders. Results: Participants in the highest suPAR quartile experienced 54% faster progression compared with the lowest quartile after adjustment for demographic and traditional CKD risk factors (P < 0.001). Addition of eGFR to the model attenuated the risk, although those in the highest quartile experienced 33% faster progression compared with the lowest quartile (P = 0.008). Plasma suPAR levels showed little change over 6 months. Limitations: Potential for residual confounding, reliance on observational data, relatively fewer patients with higher eGFRs for subgroup analysis. Conclusions: Higher suPAR levels are associated with shorter time to kidney replacement therapy or halving of eGFR in children with CKD. This association is attenuated slightly with inclusion of eGFR in regression modeling but remains a significant association for participants with the highest suPAR levels.",
keywords = "Soluble urokinase plasminogen activator receptor (suPAR), biomarker, children, chronic kidney disease (CKD), eGFR decline, end-stage renal disease (ESRD), estimated glomerular filtration rate (eGFR), pediatric, progression, renal failure",
author = "Weidemann, {Darcy K.} and Abraham, {Alison G.} and Roem, {Jennifer L.} and Furth, {Susan L.} and Warady, {Bradley A.}",
note = "Funding Information: Direct funding for the study was provided by the Marion Merrell Dow Scholarship Award of the Children{\textquoteright}s Mercy Hospital to Dr Weidemann. The funding source had no role in the study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. The CKiD Study was conducted by the CKiD Investigators and supported by the NIDDK , with additional funding from the National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute ( U01-DK-66143 , U01-DK-66174 , U01DK-082194 , U01-DK-66116 ). The data and samples from the CKiD Study reported here were supplied by the NIDDK Central Repositories. Funding Information: Darcy K. Weidemann, MD, MHS, Alison G. Abraham, PhD, Jennifer L. Roem, MS, Susan L. Furth, MD, PhD, and Bradley A. Warady, MD. Research idea and study design: DKW, BAW, SLF, AGA; data acquisition: AGA, JLR; data analysis/interpretation: DKW, AGA, JLR, SLF, BAW; statistical analysis: AGA, JLR; supervision or mentorship: BAW, SLF. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. Direct funding for the study was provided by the Marion Merrell Dow Scholarship Award of the Children's Mercy Hospital to Dr Weidemann. The funding source had no role in the study design; collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication. The CKiD Study was conducted by the CKiD Investigators and supported by the NIDDK, with additional funding from the National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U01DK-082194, U01-DK-66116). The data and samples from the CKiD Study reported here were supplied by the NIDDK Central Repositories. The authors declare that they have no relevant financial disclosures. We are grateful to Tarak Srivastava of the Children's Mercy Research Laboratory for performing plasma suPAR assays and we acknowledge the substantial contribution of all the investigators and coordinators in CKiD, in addition to all participating patients and their families. This article does not necessarily reflect the opinions or views of the CKiD Study, the NIDDK Central Repositories, or the NIDDK. Received May 20, 2019. Evaluated by 3 external peer reviewers, with direct editorial input from a Statistics/Methods Editor and an Associate Editor, who served as Acting Editor-in-Chief. Accepted in revised form November 4, 2019. The involvement of an Acting Editor-in-Chief was to comply with AJKD's procedures for potential conflicts of interest for editors, described in the Information for Authors & Journal Policies. Publisher Copyright: {\textcopyright} 2019 National Kidney Foundation, Inc.",
year = "2020",
month = aug,
doi = "10.1053/j.ajkd.2019.11.004",
language = "English (US)",
volume = "76",
pages = "194--202",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",
number = "2",
}