Kidney Tubule Aging Across Adulthood

Background: Aging is associated with declining kidney health as defined by lower eGFR and higher albuminuria. Age-related changes in kidney tubule health have not been well studied. Methods: We analyzed a subset of participants from 2 cohorts, the Coronary Artery Risk Development in Young Adults (CARDIA) Year 20 (n=939) and the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 1 (n=1,014); 780 and 668, respectively, who completed 10-year follow-up. Seven urine biomarkers were measured reflecting tubular synthetic function (EGF and UMOD), tubule reabsorption function (α1m), proximal tubular injury (IL-18 and KIM-1), and interstitial fibrosis/repair (MCP-1 and YKL-40), and were compared with albuminuria and eGFR. In pooled data, cross-sectional analyses evaluated age associations across the range of 37-84 years, and longitudinal analyses were performed to quantify changes over 10-years of follow-up. Results: Age ranges were 37-55 and 45-84 years for CARDIA and MESA at baseline, respectively; mean eGFR was 96±15 and 78±16 ml/min/1.73m 2 , and median urine albumin-to-creatinine ratios (UACR) were 4.5 [IQR: 3.3, 1.2] and 5.2 [3.3, 11] mg/g. In multivariable cross-sectional analyses, older age (per decade) was associated with higher urine α1m/UCr (23%, 95% CI: 17, 28%), IL-18/UCr (5%: 0.4, 9%), KIM-1/UCr (16%:12, 20%), MCP-1/UCr (20%: 16, 23%), YKL-40/UCr (12%: 5, 20%), UACR (30%: 23, 38%), and lower urine EGF/UCr (-13%: -15, -11%) and eGFR (-9%; -10, -8%). Age at baseline was not significantly associated with urine UMOD/UCr. In longitudinal analyses over 10-years of follow up, EGF/UCr (-20%: 95% CI: -22, -19%) and UMOD/UCr (-22%: -25, -18%) decreased and α1m/UCr (30%: 24, 35%), MCP-1/UCr (9%: 6, 13%), and YKL-40/UCr (29%: 20, 39%) increased; additionally, albuminuria increased by 29% (23, 36%) and eGFR decreased by 10% (9, 10.4%). Conclusions: In community-based adults aged 37–84 years, aging was associated with worsening tubular function and injury.