Multi-Marker Evaluation for GFR Estimation in CKD Using the 2021 CKD-EPI Equations

Background/Objectives: Chronic kidney disease (CKD) is a progressive, often irreversible condition where accurate estimation of glomerular filtration rate (GFR) is essential for staging and guiding therapy. Serum creatinine is widely used but influenced by non-renal factors, while alternative markers such as cystatin C and beta-2 microglobulin (β2M) may improve accuracy. This study evaluated the diagnostic performance of creatinine, cystatin C, and β2M for GFR estimation using the 2021 CKD-EPI equations in patients with moderate to severe CKD. Methods: This exploratory study analyzed data from 45 patients with CKD stages 3–4. Serum creatinine, cystatin C, and β2M were measured, and GFR was estimated using the 2021 CKD-EPI creatinine (eGFRcr) and creatinine–cystatin C (eGFRcr-cys) equations. Receiver operating characteristic (ROC) curve analysis was performed at a predefined threshold of 30 mL/min/1.73 m² to evaluate diagnostic accuracy in distinguishing between moderate and severe CKD. Results: Serum creatinine demonstrated high diagnostic accuracy (AUC = 0.977 for eGFRcr; 0.957 for eGFRcr-cys). Cystatin C showed perfect specificity (100%) and excellent predictive accuracy (AUC = 0.908 for eGFRcr; 0.978 for eGFRcr-cys), significantly outperforming creatinine at the severe CKD threshold (p = 0.019). β2M demonstrated balanced diagnostic performance (AUC = 0.901 for eGFRcr; 0.974 for eGFRcr-cys), with sensitivity and specificity above 90% under the eGFRcr-cys equation. Conclusions: A multi-marker evaluation using creatinine, cystatin C, and β2M within the 2021 CKD-EPI equations enhances diagnostic precision for GFR estimation in CKD. These findings provide preliminary evidence and support the clinical utility of multi-marker approaches in refining CKD staging and guiding earlier therapeutic interventions.