Analysis of the impact of female sex and muscle mass on serum creatinine and waitlist priority for liver transplantation

Model for End-Stage Liver Disease (MELD) incorporates serum creatinine (sCr), a poor measure of renal function in cirrhotic patients. Females have higher waitlist mortality, which is proposed to be due to lower muscle mass and consequent lower sCr values. This study evaluated the difference (ΔCr) between sCr and calculated creatinine (cCr) derived from measured glomerular filtration rate (mGFR) in cirrhosis. The effect of sex and muscle mass on ΔCr and MELD was studied for bias. One hundred thirty-nine cirrhotic patients assessed for liver transplantation (LT) from 2019 to 2024 were included. Forty-eight living kidney donors were the controls (n=48). The CKD-EPI equation was rearranged to determine cCr as a function of mGFR. MELD, MELD-Na, and MELD 3.0 scores were calculated using cCr and sCr; and the difference was ΔMELD, ΔMELD-Na, and ΔMELD 3.0. Skeletal muscle index (SMI, cm 2 /m 2 ) was calculated from CT images at the L3 level. Mean cCr was significantly higher than mean sCr ( p <0.001) in the study group but not the controls. In the study group, there was no difference in mean ΔCr between males (27.5±41.7 μmol/L) and females (33.9±53.1 μmol/L), p =0.45. SMI and bilirubin were independently associated with ΔCr after adjusting for sex, SMI, INR, albumin, and sodium ( p =0.01 and p =0.02, respectively). There was no difference between male and female values of ΔMELD ( p =0.76), ΔMELD-Na ( p =0.79), or ΔMELD 3.0 ( p =0.57). Low muscle mass was independently associated with ΔCr, ΔMELD, ΔMELD-Na, and ΔMELD 3.0 regardless of sex. There was also no difference in ΔCr, ΔMELD, ΔMELD-Na, and ΔMELD 3.0 between males and females in patients with measured GFR≤60 mL/min/1.73 m 2 . Serum creatinine and MELD scores are likely to be underestimated due to reduced muscle mass rather than female sex in cirrhotic patients on the LT waitlist.