Cystatin C and Creatinine Concentrations Are Uninformative Biomarkers of Sarcopenia: A Cross-Sectional NHANES Study

Differences in creatinine and cystatin C-based estimates of glomerular filtration rate (eGFR_Diff = eGFR_Cr - eGFR_CysC) may reflect differences in muscle mass. We sought to determine if eGFR_Diff (1) reflects lean mass, (2) identifies sarcopenic individuals beyond estimates based on age, body mass index (BMI), and sex; and (3) demonstrates associations differently in those with and without chronic kidney disease (CKD).

This cross-sectional study included 3,754 participants, ages 20-85 years, with creatinine and cystatin C concentration levels, and dual-energy X-ray absorptiometry scans from National Health and Nutrition Examination Survey data (1999-2006). Dual-energy X-ray absorptiometry-derived appendicular lean mass index (ALMI) estimated muscle mass. Non-race-based CKD Epidemiology Collaboration equations estimated glomerular filtration rate using eGFR_Cr, eGFR_CysC, and both biomarkers (eGFR_CysC&Cr). CKD was defined as eGFR_CysC&Cr <60 mL/minute/1.73 m². ALMI sex-specific T-scores (compared with young adult) < -2.0 defined sarcopenia. In estimating ALMI, we compared the coefficient of determination (R²) values from: 1) eGFR_Diff, 2) clinical characteristics (age, BMI, and sex), and 3) clinical characteristics plus eGFR_Diff. Using logistic regression, we evaluated each model's C-statistic to diagnose sarcopenia.

eGFR_Diff was negatively and weakly associated with ALMI (No CKD: R² = 0.006, p-value 0.002; CKD: R² = 0.001, P value .9). Clinical characteristics explained most of the variation in ALMI (No CKD: R² = 0.851, CKD: R² = 0.828), and provided strong discrimination of sarcopenia (No CKD C-statistic: 0.950; CKD C-statistic: 0.943). Adding eGFR_Diff improved the R² by 0.025, and the C-statistic by 0.003. Tests for interaction between eGFR_Diff and CKD were not significant (all P values > .05).

Although eGFR_Diff has statistically significant associations with ALMI and sarcopenia in univariate analyses, multivariate analyses demonstrate that eGFR_Diff does not capture more information beyond routine clinical characteristics (age, BMI, and sex).