IMPORTANCE: Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C-derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults. OBJECTIVE: To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD. DESIGN, SETTING, AND PARTICIPANTS: Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016. EXPOSURES: Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy. MAIN OUTCOMES AND MEASURES: The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2. RESULTS: Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34 (16) mL/min/1.73 m2. The 5-year end point-free renal survival was 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9% (95% CI, 28.7-43.0) in those in the highest quartile (P < .001). By multivariable analysis, the risk of attaining the end point was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria, and lower eGFR at baseline. In patients with baseline eGFR greater than 40 mL/min/1.73 m2, higher log-transformed suPAR levels were associated with a higher risk of CKD progression after adjustment for traditional risk factors (hazard ratio, 5.12; 95% CI, 1.56-16.7; P = .007). CONCLUSIONS AND RELEVANCE: Patients with high suPAR levels were more likely to have progression of their kidney disease. Further studies should determine whether suPAR levels can identify children at risk for future CKD.

Center for Pediatrics and Adolescent Medicine University Hospital Heidelberg Heidelberg Germany

Children's Dialysis Center Hospital St Georg Leipzig Germany

Department of Medicine Rush University Medical Center Chicago Illinois

Department of Pediatric and Adolescent Nephrology Medical University Gdańsk Gdańsk Poland

Department of Pediatric Nephrology Faculty of Medicine Cukurova University Adana Turkey

Department of Pediatric Nephrology Istanbul Medical Faculty Istanbul Turkey

Department of Pediatrics Division of Nephrology New York University Langone Medical Center New York

Division of Pediatric Nephrology Bambino Gesù Children's Hospital and Research Institute Rome Italy

Emory Clinical Cardiovascular Research Institute Division of Cardiology Emory University School of Medicine Atlanta Georgia

Harvard Medical School and Division of Nephrology Massachusetts General Hospital Charlestown

Institute of Medical Biometry and Informatics University of Heidelberg Heidelberg Germany

KfH Kidney Center for Children Marburg Germany

Nephrology Kidney Transplantation and Hypertension Children's Memorial Health Institute Warzaw Poland

Pediatric Nephrology and Dialysis Fondazione OSP Maggiore Policlinico Milano Italy

Pediatric Nephrology Charité Children's Hospital Berlin Germany

Pediatric Nephrology Children's Hospital University Medical Center Hamburg Eppendorf Hamburg Germany

Pediatric Nephrology Ege University Faculty of Medicine Izmir Turkey

Pediatric Nephrology Giannina Gasline Institute Genova Italy

Pediatric Nephrology Hacettepe University Faculty of Medicine Ankara Turkey

Pediatric Nephrology Vienna University Children's Hospital Vienna Austria

Pediatrics Hospital São João Porto Portugal

Pediatrics University Hospital Motol Prague Czech Republic

The Research Institute at Nationwide Children's Hospital The Ohio State University Columbus

University Children's Hospital Belgrade Belgrade Serbia

Vilnius University Pediatric Center Vilnius Lithuania

JAMA Pediatr. 2017 Nov 1;171(11):1127. doi: 10.1001/jamapediatrics.2017.3864. PubMed

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