Impact of Muscle Mass on the Performance of Creatinine-Based eGFR Equations and Mortality Risk Assessment After Kidney Transplantation

Background

Estimating glomerular filtration rate (eGFR) in kidney transplant recipients (KTR) typically relies on plasma creatinine, which is influenced by muscle mass. Reduced muscle mass is suspected to reduce eGFR performance in this population but this effect has not been rigorously evaluated. This study quantified the impact of muscle mass on eGFR accuracy and its confounding effect on the association between kidney function and mortality in KTR.

Methods

We studied a prospective and consecutive cohort of 1829 KTR (mean age 52 ± 14 years; 38.9% female) who underwent GFR measurement using iohexol clearance (ioGFR). Muscle mass was assessed by creatinine excretion rate (CER) from timed urine collections. We evaluated the impact of muscle mass on the performance of five eGFR equations (MDRD, CKDEPI₂₀₀₉, CKDEPI₂₀₂₁, EKFC and RFKTS) using multiple regression and subgroup analysis. The association between eGFRs, ioGFR and mortality was examined using Cox proportional hazards models.

Results

All eGFR equations showed a significant negative correlation with CER. EKFC was the least sensitive to CER (β coefficient 95% confidence interval [CI]: −0.17 to −0.12). All eGFR equations demonstrated reduced accuracy in the lowest muscle mass tertile. In multivariable analyses, ioGFR was significantly associated with mortality (hazard ratio 95% CI: 0.972–0.995) but eGFRs were not. Including CER in the Cox models resulted in convergence of the mortality hazard ratios for ioGFR and eGFRs (hazard ratio 95% CI: ioGFR: 0.98–0.999; MDRD: 0.98–0.999; CKDEPI₂₀₂₁: 0.99–1; EKFC (0.98–1) RFKS: 0.98–0999).

Conclusion

The performance of all tested creatinine-based eGFR equations is strongly impacted by muscle mass. Muscle mass is also a key confounder in the mortality risk assessment using eGFR. Incorporating muscle mass into KTR's evaluations may improve kidney function assessments in KTR.