Urinary excretion of epidermal growth factor and rapid loss of kidney function

• Published in: Nephrology Dialysis Transplantation
• Main Authors: Norvik, Jon Viljar, Harskamp, Laura R., Nair, Viji, Shedden, Kerby, Solbu, Marit Dahl, Eriksen, Bjørn Odvar, Kretzler, Matthias, Gansevoort, Ron T., Ju, Wenjun, Melsom, Toralf
• Format: Article in Journal/Newspaper
• Language: English
• Published: Oxford University Press 2020
• Subjects: VDP::Medical disciplines: 700::Basic medical; dental and veterinary science disciplines: 710; VDP::Medisinske Fag: 700::Basale medisinske; odontologiske og veterinærmedisinske fag: 710; Melsom; Norvik; Norway; Solbu; Tromso
• Online Access: https://hdl.handle.net/10037/20852; https://doi.org/10.1093/ndt/gfaa208

This is a pre-copyedited, author-produced version of an article accepted for publication in Nephrology Dialysis Transplantation following peer review. The version of record Norvik JV, Harskamp, Nair V, Shedden, Solbu MD, Eriksen BO, Kretzler M, Gansevoort RT, Ju W, Melsom T. Urinary excretion of epidermal growth factor and rapid loss of kidney function. Nephrology, Dialysis and Transplantation. 2020, is available online at: https://doi.org/10.1093/ndt/gfaa208 Background - Lower urinary excretion of the kidney tubule–specific biomarker epidermal growth factor (uEGF) is associated with increased risk of renal function [glomerular filtration rate (GFR)] loss in diabetes and in patients with established chronic kidney disease (CKD). We investigated whether uEGF is associated with rapid GFR decline or incident CKD in the general population. Methods - Subjects without CKD or diabetes were recruited from the general population in Tromso, Norway [Renal Iohexol Clearance Survey (RENIS); N = 1249] and Groningen, the Netherlands [Prevention of REnal and Vascular END-stage disease (PREVEND); N = 4534], with a median follow-up of 5.6 and 7.4 years, respectively. GFR was measured by iohexol clearance in the RENIS and estimated using the CKD Epidemiology Collaboration creatinine–cystatin C equation in the PREVEND study. Rapid GFR decline was defined as an annual GFR loss >3.0 mL/min/1.73 m 2 and in sensitivity analyses as subjects with the 10% steepest GFR slope within each cohort. Results - Lower baseline uEGF excretion was associated with rapid GFR loss in both cohorts {RENIS, odds ratio [OR] per 1 μg/mmol lower uEGF 1.42 [95% confidence interval (CI) 1.06–1.91], P = 0.02; PREVEND, OR 1.29 [95% CI 1.10–1.53], P < 0.01}, adjusted for baseline GFR, albumin:creatinine ratio and conventional CKD risk factors. Similar results were obtained using the outcome of the 10% steepest GFR slope in each cohort. Lower uEGF levels were associated with incident CKD in the combined analysis of both cohorts. Conclusions - Lower uEGF levels are associated with increased risk of rapid GFR loss and incident CKD in the general population. This finding, together with previous findings in CKD and high-risk populations, supports that uEGF may serve as a broadly applicable biomarker representing the tubular component of the current glomerulus-centric clinical risk assessment system.