Kidney Tubular Biomarkers Worsen With Aging Across Two Community Cohorts

Age-related kidney decline is commonly assessed using eGFR and albuminuria, but changes in tubular health are less well characterized. Researchers analyzed 939 CARDIA and 1,014 MESA participants aged 37–84 years, measuring seven urinary biomarkers of tubular synthesis, reabsorption, injury, and fibrosis or repair. The observational study combined cross-sectional age comparisons with 10-year longitudinal analyses in 780 CARDIA and 668 MESA participants.

In adjusted cross-sectional analyses, each additional decade of age was associated with 23% higher urine α1-microglobulin, 16% higher KIM-1, and 20% higher MCP-1, all indexed to urine creatinine. EGF was 13% lower, eGFR was 9% lower, and urine albumin-to-creatinine ratio was 30% higher. Baseline age was not significantly associated with urinary uromodulin.

Over 10 years, creatinine-indexed EGF fell 20% (95% CI, 19%–22%) and uromodulin fell 22% (18%–25%). α1-microglobulin increased 30%, MCP-1 increased 9%, and YKL-40 increased 29%. Albuminuria rose 29%, while eGFR declined 10%.

These findings suggest that kidney aging involves changes in tubular function and injury markers alongside conventional measures of kidney health. However, the observational design cannot establish causality, and the reported outcomes are biomarkers rather than clinical events. The study does not establish whether routine tubular biomarker testing improves patient care.