RATIONALE AND OBJECTIVE: In the Lifestyle Interventions and Independence for Elders (LIFE) trial, a structured exercise intervention slowed kidney function decline in sedentary older adults. Biomarkers of kidney health could distinguish potential mechanisms for this beneficial effect. STUDY DESIGN: Randomized controlled trial. SETTING AND POPULATION: A total of 1,381 sedentary adults aged 70 to 89 years enrolled in the LIFE trial. INTERVENTION: Structured, 2-year, moderate-intensity exercise intervention versus health education. OUTCOMES: Physical activity was measured by step count. Primary outcomes were changes in 14 serum and urine biomarkers of kidney health collected at baseline, year 1, and year 2. We determined the effect of randomization on changes in kidney measures and then evaluated observational associations of achieved activity on each measure. RESULTS: Participants assigned to exercise walked on average 291 more steps per day than participants assigned to health education. The intervention was not significantly associated with changes in biomarkers of kidney health. In observational analyses, persons in the highest versus lowest quartile of activity (>= 3,470 versus < 1,568 steps/day) had significant improvement in urine albumin (mean -0.22 mg albumin/g urine creatinine (interquartile range (IQR) -0.37 to -0.06)), alpha-1-microglobulin (-0.18 mg/L (-0.28 to -0.08)), trefoil factor-3 (-0.24 pg/mL (-0.35 to -0.13)), epidermal growth factor (0.19 pg/mL (0.06 to 0.32)), uromodulin (0.06 pg/mL (0.00 to 0.12)), interleukin 18 (-0.09 pg/mL (-0.15 to -0.03)), neutrophil gelatinase-associated lipocalin (-0.16 pg/mL (-0.24 to -0.07)), monocyte chemoattractant protein-1 (-0.25 pg/mL (-0.36 to -0.14)), clusterin (-0.16 pg/mL (-0.30 to -0.02)), serum tumor necrosis factor receptor-1 (-0.25 mg/dL (-0.39 to -0.11)) and tumor necrosis factor receptor-2 (-0.30 mg/dL (-0.44 to -0.16)). In sensitivity analyses, incremental changes in activity were most impactful on urine interleukin 18 and serum tumor necrosis factor-1. LIMITATIONS: The original study was not designed to assess the impact on kidney health. Non-white individuals and patients with advanced chronic kidney disease are underrepresented. CONCLUSIONS: Randomization to structured exercise did not improve kidney health at a group level. However, higher exercise was associated with concurrent improvements in biomarkers of glomerular injury, tubular function/repair, tubular injury, generalized inflammation, and tubulointerstitial repair/fibrosis.

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