Cystatin C- and Creatinine-Based Glomerular Filtration Rate Estimation Differences and Muscle Quantity and Functional Status in Older Adults: The Health, Aging, and Body Composition Study

RATIONALE & OBJECTIVE: The difference in the estimated glomerular filtration rate based on cystatin C and that based on creatinine (eGFRDiff) is known to be associated with frailty and mortality. Creatinine is influenced by muscle mass, more so than cystatin C; we aimed to determine whether eGFRDiff is associated with muscle quantity and to what extent muscle quantity explains the relationship between eGFRDiff and poor functional status. STUDY DESIGN: A cohort analysis of the health, aging, and body composition study (HABC). SETTING & PARTICIPANTS: Overall, 2,970 HABC participants had their baseline serum creatinine level, cystatin C level, and body composition measured using imaging. EXPOSURE: Estimated glomerular filtration rates (eGFRs) were calculated using Chronic Kidney Disease Epidemiology Collaboration equations (estimated glomerular filtration rate based on cystatin C [eGFR(Cys)] and estimated glomerular filtration rate based on creatinine [eGFR(Cr)]), and eGFRDiff was calculated as eGFR(Cys) − eGFR(Cr). OUTCOMES: The total thigh muscle area was evaluated using computed tomography. The health, aging, and body composition study physical performance battery was scored on a continuous scale (standing and walking tasks); poor functional status was characterized by the lowest quartile. ANALYTICAL APPROACH: We used linear regression to model the cross-sectional association of eGFRDiff and muscle measures. We used logistic regression to evaluate the association of eGFRDiff with poor functional status. RESULTS: The mean age was 74 ± 3 years; the eGFR(Cys), eGFR(Cr), and eGFRDiff was 72 ± 18, 68 ± 15, and 4 ± 14 mL/min/1.73 m(2), respectively. Compared with participants in the reference group (−10 < eGFRDiff ≤ 10 mL/min/1.73 m(2)), those in the negative eGFRDiff group (≤−10 mL/min/1.73 m(2)) were more likely to have comorbidities, a slower gait, and worse functional status. They had an approximately 14-cm(2) smaller thigh muscle area in a fully adjusted model. Compared with the reference group, those in the negative group had 1.89-fold higher odds of poor functional status (unadjusted). This relationship was minimally attenuated after adjustment for thigh muscle, thigh fat area, appendicular lean mass, and limb fat mass, both individually and in combination. LIMITATIONS: The functional status outcome was specific to HABC. The muscle measures did not capture dynamic turnover. CONCLUSIONS: The difference of eGFR(Cys) − eGFR(Cr) provides information on older adults’ functional status, which is only partially explained by muscle quantity and quality.