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

Jon Viljar Norvik; Laura R Harskamp; Viji Nair; Kerby Shedden; Marit D Solbu; Bjørn O Eriksen; Matthias Kretzler; Ron T Gansevoort; Wenjun Ju; Toralf Melsom

doi:10.1093/ndt/gfaa208

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

Nephrol Dial Transplant. 2021 Sep 27;36(10):1882-1892. doi: 10.1093/ndt/gfaa208.

Authors

Jon Viljar Norvik^{1

2}, Laura R Harskamp³, Viji Nair⁴, Kerby Shedden⁵, Marit D Solbu^{1

2}, Bjørn O Eriksen^{1

2}, Matthias Kretzler^{4

6}, Ron T Gansevoort³, Wenjun Ju^{4

6}, Toralf Melsom^{1

2}

Affiliations

¹ Metabolic and Renal Research Group, UiT The Arctic University of Norway, Tromsø, Norway.
² Section of Nephrology, University Hospital of North Norway, Tromsø, Norway.
³ Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁴ Department of Internal Medicine/Nephrology, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Statistics, University of Michigan, Ann Arbor, MI, USA.
⁶ Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.

Abstract

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 m2 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.

Keywords: chronic kidney disease; clinical epidemiology; epidermal growth factor; renal function decline; uEGF.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Creatinine
Disease Progression
Epidermal Growth Factor* / urine
Glomerular Filtration Rate
Humans
Kidney / physiopathology*
Netherlands
Norway
Renal Insufficiency, Chronic* / diagnosis

Substances

Epidermal Growth Factor
Creatinine

Abstract

Publication types

MeSH terms

Substances

Grants and funding