The Precision and Accuracy of CKD–EPI Creatinine, Cystatin-C, and Creatinine–Cystatin-C Equations in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis

Rationale & Objective Cystatin-C offers advantages over creatinine for estimating glomerular filtration rate (GFR) due to reduced dependence on muscle mass. Although the 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines support its use in chronic kidney disease, specific guidance for kidney transplant recipients (KTRs) remains limited. This systematic review and meta-analysis evaluated the precision and accuracy of cystatin-C–based, creatinine-based, and combined creatinine–cystatin-C equation compared with measured GFR in KTRs. Study Design Systematic review and meta-analysis. Setting & Study Populations Published studies evaluating the performance of CKD-EPI equations among adult KTRs. Selection Criteria for Studies Peer-reviewed studies reporting CKD-EPI–based estimated GFR (eGFR) compared with measured GFR, including data on mean bias and/or accuracy metrics (P30 or P10). Data Extraction Two reviewers independently extracted study characteristics, GFR measurement methods, equation type, mean bias, and accuracy outcomes. Discrepancies were resolved through consensus. Analytical Approach Random-effects meta-analyses were performed to estimate pooled mean bias and accuracy within 30% (P30) and 10% (P10) of measured GFR, with 95% confidence intervals (CIs). Heterogeneity was quantified using the I 2 statistic. Results Twenty-six studies met inclusion criteria; 14 provided extractable CKD-EPI bias data (4,041 adult KTRs; 11,997 repeated measures). The combined creatinine–cystatin-C equation had the lowest pooled mean bias (0.63 mL/min/1.73 m 2 ; 95% CI, −3.65 to 4.92). Creatinine-based equations underestimated measured GFR (−4.95 mL/min/1.73 m 2 ; 95% CI, −9.10 to −0.81), while cystatin-C–based equations overestimated it (5.01 mL/min/1.73 m 2 ; 95% CI, 0.54 to 9.48). P30 and P10 accuracies were broadly similar across biomarkers. Limitations Heterogeneity in GFR measurement methods, assay calibration, and timing post-transplant. Conclusions Across heterogeneous KTR studies, the CKD-EPI creatinine–cystatin C equation demonstrates lower mean bias and slightly higher pooled P30 than single-marker equations in population-level assessment. When cystatin C is available, the combined equation is a reasonable choice. Further multicenter validation studies with harmonized biomarker protocols are needed to confirm its clinical utility in KTRs. Plain-Language Summary Accurate estimation of kidney function is essential in kidney transplant recipients. Creatinine is widely used but can be influenced by muscle mass and other non–kidney-related factors. Cystatin C has been proposed as an alternative marker that may reduce some of these limitations; however, evidence in transplant recipients remains limited. This systematic review and meta-analysis compared creatinine-based, cystatin C–based, and combined equations with directly measured kidney function. Equations combining creatinine and cystatin C provided more balanced estimates overall. However, differences in study methods and transplant-related factors may affect individual results. These findings support use of the combined equation when cystatin C is available and emphasize the need for further validation in transplant populations.