Glomerular Filtration of Creatinine: Validation of a Novel Index of Muscle Mass Among Older Adults

Rationale & objective: Low muscle mass is common among older adults and associated with poor prognosis. Quantifying muscle mass is challenging in routine clinical practice. We hypothesized that glomerular filtration of creatinine (GF_cr) reflects muscle mass, and previously proposed estimated GF_cr (eGF_cr), as a practical index of muscle mass in older adults. This study investigated whether measured GF_cr (mGF_cr) and eGF_cr are similarly associated with the direct measure of muscle mass, the thigh total muscle lean area (TTMLA).

Study design: Cross-sectional analysis of a community-based prospective cohort.

Setting & participants: A total of 794 older adults with measured glomerular filtration rate (mGFR) and TTMLA in the AGES-Reykjavik Study.

Exposure: Measured GF_cr, the product of serum creatinine (Scr) and mGFR obtained using plasma iohexol clearance and eGF_cr, the product of Scr and estimated glomerular filtration rate using serum cystatin C (Scys).

Outcome: TTMLA measured using computed tomography.

Analytical approach: Sex-specific Pearson's correlation and linear regression analyses using continuous and categorical mGF_cr and eGF_cr. Covariates included demographic, behavioral, and clinical variables, and comorbid conditions.

Results: The mean age and mGFR were 80.3±4.0 (SD) years and 62.3±16.5 (SD) mL/min/1.73m², respectively. The lowest sex-specific tertile of mGF_cr, compared with the highest tertile, was associated with a 14.6 (95% CI, 11.5-17.6) cm²/1.73m² lower TTMLA in men, and a 7.9 (95% CI, 5.5-10.2) cm²/1.73m² lower TTMLA in women. Significant associations were observed between eGF_cr and TTMLA. Correlations of eGF_cr with TTMLA were generally as strong or stronger than correlations of alternative indices derived from Scr and Scys.

Limitations: Residual confounding by measured and unmeasured variables.

Conclusions: These findings support the validity of GF_cr as an index of muscle mass among older adults and the use of eGF_cr as a practical alternative to mGF_cr in the clinical setting.

Plain-language summary: Low muscle mass is common among older adults and is associated with poor clinical outcomes. Quantifying muscle mass is challenging in routine clinical practice. We evaluated whether glomerular filtration of creatinine (GF_cr) could serve as an index of muscle mass. We performed a cross-sectional study including 794 older adults who underwent computed tomography for thigh muscle lean area as a directly measured indicator of total body muscle mass. Significant positive associations between thigh muscle lean area and both measured GF_cr (serum creatinine [Scr] ×measured glomerular filtration rate [GFR]) and estimated GF_cr (Scr ×estimated GFR based on serum cystatin C [Scys]), a more practical index, were shown. These findings suggest the value of using eGF_cr, a simply obtained novel index in the clinical setting, to assess muscle mass among older adults.