Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies

Overview

Journal Kidney Med

Specialty Nephrology

Date 2024 Jun 3

PMID 38826568

Authors

Jonathan G Amatruda

Ronit Katz

Casey M Rebholz

Mark J Sarnak

Orlando M Gutierrez

Sarah J Schrauben

Jason H Greenberg

Josef Coresh

Mary Cushman

Sushrut Waikar

Chirag R Parikh

Jeffrey R Schelling

Manasi P Jogalekar

Joseph V Bonventre

Ramachandran S Vasan

Paul L Kimmel

Joachim H Ix

Michael G Shlipak

Affiliations

Soon will be listed here.

Abstract

Rationale & Objective: Tubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.

Study Design: Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).

Setting & Participants: Adults with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m and without diabetes in the ARIC, REGARDS, and MESA studies.

Exposures: Baseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1, epidermal growth factor, and chitinase-3-like protein 1.

Outcome: Incident CKD or end-stage kidney disease.

Analytical Approach: Multivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all 3 cohorts.

Results: 872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60 ± 10 to 63 ± 8 years, and baseline eGFR ranged from 88 ± 13 to 91 ± 14 mL/min/1.73 m. In ARIC, higher concentrations of urine MCP-1, α1m, and kidney injury molecule-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of epidermal growth factor were each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all 3 cohorts, each 2-fold increase α1m concentration was associated with incident CKD (HR, 1.19; 95% CI, 1.08-1.31).

Limitations: Observational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to 3 cohorts.

Conclusions: In 3 combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m concentration was independently associated with incident CKD. 4 biomarkers were associated with incident CKD in at least 1 of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.

Citing Articles

GDF15, EGF, and Neopterin in Assessing Progression of Pediatric Chronic Kidney Disease Using Artificial Intelligence Tools-A Pilot Study.

Musial K, Stojanowski J, Bargenda-Lange A, Golebiowski T Int J Mol Sci. 2025; 26(5).

PMID: 40076962 PMC: 11899747. DOI: 10.3390/ijms26052344.

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