Biomarkers of Kidney Health and Dual Trajectories of Cognitive and Physical Function in Older Adults: Health Aging and Body Composition Study Findings.

KEY POINTS: Urine albumin-to-creatinine ratio was associated with multiple dual trajectory groups, while eGFR was only associated with dual decline. Lower α -klotho was associated with dual cognitive-physical decline versus no decline in either process. In healthy older adults, kidney biomarkers may potentially predict long-term cognitive and physical performance.

BACKGROUND

Kidney disease contributes to both cognitive and physical decline; whether kidney health biomarkers relate to declining cognitive and physical performance separately and/or together is unknown.

METHODS

Among 1902 participants (26% Black; 53% female) in the Health, Aging, and Body Composition Study with intact baseline gait speed (≥0.8 m/s) and cognition (modified mini-mental state score ≥90), we assessed baseline kidney-related biomarkers (eGFR, urine albumin-to-creatinine ratio, serum 25-hydroxyvitamin D, plasma intact parathyroid hormone, plasma α -klotho, serum intact fibroblast growth factor 23, and vitamin D metabolites) with joint trajectories of cognitive and physical performance. Grouped-based trajectory analysis of modified mini-mental state and 20-m usual gait speed up to 10 years yielded three groups: group 1 ( n =660), superior longitudinal cognitive-physical performance; group 2 ( n =744), high sustained cognition and initially lower, declining gait; and group 3 ( n =498), lower initial cognitive-physical performance, both steeply declining. Three sequential multinomial regression models were built with covariate adjustment.

RESULTS

In model 1 (kidney function), higher eGFR (per 10 ml/min per 1.73 m 2 ) was associated with lower odds of being in group 3 versus group 1 (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75 to 0.94; P = 0.003) after covariate adjustment. In addition, each doubling of urine albumin-to-creatinine ratio related to higher odds of being in group 2 (OR, 1.13; 95% CI, 1.04 to 1.23; P = 0.006) and group 3 (OR, 1.23; 95% CI, 1.12 to 1.36; P < 0.001) versus group 1. Log2 25-hydroxyvitamin D and log2 intact parathyroid hormone, added in model 2 (clinical biomarkers), were not significantly associated with cognitive-physical trajectory ( P = 0.63, model 2 versus model 1). However, model 3 (research biomarkers adding α -klotho and fibroblast growth factor 23) showed higher log-2 α -klotho associated with lower odds of being in group 3 versus 1 (OR, 0.70; 95% CI, 0.52 to 0.94; P = 0.019).

CONCLUSIONS

Kidney health biomarkers are potential factors in dual maintenance/decline in cognitive-physical function. Improving kidney health may contribute to preserved function in older adults.