A Prospective Study of the Association Between Plasma Calprotectin Levels and New-Onset CKD in the General Population

Arno R Bourgonje; Martin F Bourgonje; Sacha la Bastide-van Gemert; Tom Nilsen; Clara Hidden; Ron T Gansevoort; Douwe J Mulder; Jan-Luuk Hillebrands; Stephan J L Bakker; Robin P F Dullaart; Harry van Goor; Amaal E Abdulle

doi:10.1016/j.ekir.2024.02.1392

A Prospective Study of the Association Between Plasma Calprotectin Levels and New-Onset CKD in the General Population

Kidney Int Rep. 2024 Feb 16;9(5):1265-1275. doi: 10.1016/j.ekir.2024.02.1392. eCollection 2024 May.

Authors

Affiliations

¹ Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
² The Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
³ Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁴ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁵ Gentian AS, Moss, Norway.
⁶ Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁷ Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁸ Department of Internal Medicine, Division of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Abstract

Introduction: Systemic inflammation has been associated with chronic kidney disease (CKD). In this study, we aimed to investigate a potential association between the plasma biomarker of inflammation calprotectin and new-onset CKD in a population-based cohort study.

Methods: Individuals without CKD at baseline (n = 4662) who participated in the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) prospective population-based cohort study in the Netherlands were included. Baseline plasma calprotectin levels were assessed in samples that had been stored at -80 °C. Occurrence of new-onset CKD was defined as a composite outcome of an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m², urinary albumin excretion (UAE) >30 mg/24h, or both.

Results: Baseline median (interquartile range) plasma calprotectin levels were 0.49 (0.35-0.68) mg/l and baseline median eGFR was 95.9 (interquartile range: 85.0-105.7) ml/min per 1.73 m². After median follow-up of 8.3 (7.8-8.9) years, 467 participants developed new-onset CKD. Baseline plasma calprotectin levels were significantly associated with an increased risk of new-onset CKD (hazard ratio [HR] per doubling 1.28 [95% confidence interval, CI: 1.14-1.44], P < 0.001), independent of potentially confounding factors (HR 1.14 [95% CI: 1.01-1.29], P = 0.034), except for baseline high-sensitive C-reactive protein (hs-CRP) (HR 1.05 [0.91-1.21], P = 0.494). In secondary analyses, the association between plasma calprotectin and occurrence of UAE >30 mg/24h remained significant (HR 1.17 [1.02-1.34], P = 0.027), but not significantly so for the incidence of eGFR <60 ml/min per 1.73 m² as individual outcome (HR 1.15 [0.92-1.43], P = 0.218).

Conclusion: Higher plasma calprotectin levels are associated with an increased risk of developing CKD in the general population. This association is mitigated after adjustment for hs-CRP, and more pronounced with new-onset CKD defined by UAE.

Keywords: biomarker; calprotectin; chronic kidney disease; epidemiology; inflammation; population science.