Structured moderate exercise and biomarkers of kidney health in sedentary older adults: the lifestyle interventions and independence for elders randomized clinical trial

Authors: SHESHANDRI, ANOOP - University Of California San Francisco (UCSF); LAI, MASON - University Of California San Francisco (UCSF); HSU, FANG-CHI - Wake Forest Baptist Medical Center; BAUER, SCOTT - University Of California San Francisco (UCSF); CHEN, SHYH-HUEI - Wake Forest Baptist Medical Center; TSE, WARREN - University Of California San Francisco (UCSF); JOTWANI, VASANTHA - University Of California San Francisco (UCSF); TRANAH, GREGORY - California Pacific Medical Center Research Institute; LAI, JENNIFER - University Of California San Francisco (UCSF); HALLAN, STEIN - Norwegian University Of Science And Technology; FIELDING, ROGER - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LIU, CHRISTINE - Stanford University; LI, JOACHIM - University Of California, San Diego; COCA, STEVEN - The Icahn School Of Medicine At Mount Sinai; SHLIPAK, MICHAEL - University Of California San Francisco (UCSF)

Submitted to: Kidney Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/5/2023
Publication Date: 9/12/2023
Citation: Sheshandri, A., Lai, M., Hsu, F., Bauer, S., Chen, S., Tse, W., Jotwani, V., Tranah, G.J., Lai, J.C., Hallan, S., Fielding, R., Liu, C.K., Li, J.H., Coca, S.G., Shlipak, M.G. 2023. Structured moderate exercise and biomarkers of kidney health in sedentary older adults: the lifestyle interventions and independence for elders randomized clinical trial. Kidney Medicine. https://doi.org/10.1016/j.xkme.2023.100721.
DOI: https://doi.org/10.1016/j.xkme.2023.100721

Interpretive Summary: We previously showed that regular exercise slowed the decline in kidney function observed with aging. In this study we evaluated mechanisms by which exercise might slow kidney function decline. We measured a panel of kidney function markers in the blood and urine of older men and women who were assigned by the flip of a coin to a physical activity or health education program for two years. Overall, there were no differences in kidney function markers between the physical activity and health education groups. However, participants with the highest levels of physical activity had improvements in urine markers of kidney function and lower levels of some markers of inflammation in the blood. These results suggest that higher amounts of physical activity may improve markers of kidney function and reduce inflammation.

Technical Abstract: 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: 1381 sedentary adults aged 70-89 years in LIFE Intervention: Structured, two-year, moderate-intensity exercise intervention vs health education (HE) 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 then evaluated observational associations of achieved activity on each measure. Results: Participants assigned to exercise walked on average 291 more steps/day than participants assigned to HE. 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 (=3470 vs. <1568 steps/day) had significant improvement in urine albumin (- 0.22 mg ACR, [-0.37, -0.06]), alpha-1-microglobulin (-0.18 mg/L, [-0.28, -0.08]), trefoil factor-3 (-0.24 pg/mL, [-0.35, -0.13]), epidermal growth factor (0.19 pg/mL, [0.06, 0.32]), uromodulin(0.06 pg/mL, [0.00, 0.12]), interleukin-18 (-0.09 pg/mL, [-0.15, -0.03]), neutrophil gelatinase associated lipocalin (-0.16 pg/mL, [-0.24, -0.07]), monocyte chemoattractant protein-1 (-0.25 pg/mL, [-0.36, -0.14]), clusterin (-0.16 pg/mL, [-0.30, -0.02]), serum tumor necrosis factor receptor-1 (-0.25 mg/dL, [-0.39, -0.11]) and tumor necrosis factor receptor-2 (-0.30 mg/dL, [-0.44, -0.16]). In sensitivity analyses, incremental changes in activity were most impactful on urine interleukin-18 and serum tumor necrosis factor-1. Limitations: Original study not designed for impact on kidney health. Underrepresented in nonwhite individuals and advanced CKD. 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.