The Precision and Accuracy of Chronic Kidney Disease Epidemiology Collaboration 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) because of its 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- and cystatin C-based equations compared with measured GFR in KTRs.

STUDY

DESIGN

Systematic review and meta-analysis.

SETTING & STUDY POPULATIONS: Published studies evaluating the performance of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations among adult KTRs.

SELECTION CRITERIA FOR STUDIES: The 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 I2 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 m2; 95% CI, -3.65 to 4.92). Creatinine-based equations underestimated measured GFR (-4.95 mL/min/1.73 m2; 95% CI, -9.10 to -0.81), whereas cystatin C-based equations overestimated it (5.01 mL/min/1.73 m2; 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.

REGISTRATION: PROSPERO (CRD42024506221).