Comparative validation of serum creatinine- and cystatin C-based surrogate markers for skeletal muscle mass in patients with non-dialysis chronic kidney disease

Abstract Background Sarcopenia, characterized by reduced skeletal muscle mass (SMM) and diminished muscle strength and/or decreased physical activity, poses a significant morbidity and mortality risk in patients with non-dialysis chronic kidney disease (CKD). Indices based on serum creatinine (SCr) and cystatin C (SCystC) have been proposed to estimate SMM in this population; however, few studies have compared these indices with SMM measured using bioelectrical impedance analysis in terms of accuracy and agreement. Methods In this cross-sectional study, we evaluated 90 patients with non-dialysis CKD with appendicular SMM data quantified via bioelectrical impedance analysis. We examined several SCr- and SCystC-based indices, including the SCr/SCystC ratio, SCystC-based estimated glomerular filtration rate/SCr-based estimated glomerular filtration rate ratio, the difference between these estimated glomerular filtration rates, the product of the SCr- and SCystC-based estimated glomerular filtration rates, estimated 24-h urinary creatinine excretion, and SMM estimates calculated using the formulas of Kim, Sunayama, and Hsu. Results All indices exhibited significant correlations with appendicular SMM measured using bioelectrical impedance analysis, with correlation coefficients of 0.41–0.87. Bland–Altman analysis demonstrated good agreement. Notably, indices incorporating body weight showed stronger correlations than those based solely on SCr and SCystC; however, these formulas are more complex, reflecting a trade-off between accuracy and simplicity. Conclusions Our data showed that although these biochemical indices cannot fully replace SMM measured using bioelectrical impedance analysis or other reliable methods, they offer simple, practical tools for identifying patients with non-dialysis CKD at an increased risk of low muscle mass and sarcopenia.