Can muscle loss make kidney function estimates misleading?

Muscle loss is particularly relevant to kidney assessment in older adults because serum creatinine reflects both filtration and creatinine generation from skeletal muscle. In an 84-year-old man with substantial sarcopenia, frailty, wasting, or major lean-mass loss, a “normal” or low creatinine should not by itself be taken as reassuring evidence of normal kidney filtration.

Mechanistic and clinical evidence

• Creatinine arises from nonenzymatic turnover of creatine and phosphocreatine; approximately 90–95% of the body creatine pool is in skeletal muscle, with roughly 1.6–2% turning over daily. Loss of muscle therefore reduces endogenous creatinine production.
• Lower production can lower serum creatinine independently of true GFR. Creatinine-only eGFR may consequently overestimate filtration and make chronic kidney dysfunction appear less severe or remain unrecognized.
• Human observations support this direction: after marked bariatric-surgery weight loss, lean limb mass and serum creatinine declined while creatinine-based eGFR rose, despite no material change in measured GFR or cystatin-C-based estimates. The size of the bias varies with the magnitude and composition of weight loss, diet, creatine/meat intake, body size, and other factors.

Assessment when accuracy matters

• KDIGO 2024 identifies altered muscle mass as a setting in which creatinine-based eGFR can be inaccurate. When GFR informs medication dosing, diagnostic classification, or other consequential decisions, a same-sample combined creatinine–cystatin C eGFR is recommended.
• Cystatin C reduces muscle-related bias but is not infallible: in neuromuscular disease, even cystatin-C equations overestimated iohexol-measured GFR by about 22 mL/min/1.73 m² on average; thyroid disease and corticosteroids can also affect it.
• If combined estimation remains questionable or a more precise value would change management, measured GFR using an exogenous filtration marker is appropriate.

Bottom line

• The claim is well supported: substantial muscle loss can reduce creatinine production, causing creatinine-based eGFR to overstate true filtration and underrecognize kidney dysfunction.