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Multi-Marker Evaluation of Creatinine, Cystatin C and β2-Microglobulin for GFR Estimation in Stage 3-4 CKD Using the
Nurulamin Abu Bakar1, Nurul Izzati Hamzan2, Siti Nurwani Ahmad Ridzuan2
1Centre of Diagnostics, Therapeutics and Investigative Studies (CODTIS), Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.
Insights
Accurate chronic kidney disease (CKD) staging is crucial. This study found that serum creatinine, cystatin C, and β2-microglobulin (β2M) effectively differentiate CKD stages 3 and 4, supporting multi-marker evaluation.
Area of Science:
- Nephrology
- Biomarker Discovery
- Clinical Diagnostics
Background:
- Accurate glomerular filtration rate (GFR) estimation is vital for chronic kidney disease (CKD) management.
- Serum creatinine is a common GFR marker but is affected by non-renal factors.
- Cystatin C and β2-microglobulin (β2M) offer potential complementary information regarding filtration, tubular function, and inflammation.
Purpose of the Study:
- To compare the discriminatory performance of creatinine, cystatin C, and β2M in staging CKD stages 3-4.
- To evaluate these markers within the 2021 CKD-EPI eGFR framework.
- To assess the utility of a multi-marker approach for CKD staging.
Main Methods:
- Study included 45 adults with CKD stages 3-4.
- CKD staging used 2021 CKD-EPI creatinine (eGFRcr) and creatinine-cystatin C (eGFRcr-cys) equations with a 30 mL/min/1.73 m² threshold.
- Receiver operating characteristic (ROC) analysis assessed marker performance for distinguishing moderate from severe CKD.
Main Results:
- Creatinine demonstrated high diagnostic accuracy (AUC up to 0.98).
- Cystatin C achieved 100% specificity for severe CKD and showed diagnostic accuracy comparable to creatinine (AUC 0.978 vs. 0.957) in the eGFRcr-cys framework.
- β2M showed AUCs up to 0.97 with >90% sensitivity and specificity.
Conclusions:
- The findings support using a multi-marker evaluation for CKD staging within the 2021 CKD-EPI framework.
- This approach may be more informative than relying on a single marker or validation against measured GFR alone.
- Larger studies are needed to incorporate measured GFR and clinical confounders.
Abstract:
Chronic kidney disease (CKD) is a progressive disease in which 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 cystatin C and β2-microglobulin (β2M) may provide complementary information related to filtration and tubular or inflammatory factors. This study compared the discriminatory performance of creatinine, cystatin C and β2M for separating CKD stage 3 from stage 4 within the 2021 CKD-EPI eGFR framework in 45 adults with CKD stages 3-4. CKD stage classification was defined using the 2021 CKD-EPI creatinine and creatinine-cystatin C equations (eGFRcr, eGFRcr-cys) with a threshold of 30 mL/min/1.73 m2. Receiver operating characteristic (ROC) analysis evaluated each marker's ability to distinguish moderate from severe CKD. Creatinine showed high diagnostic accuracy (AUC up to 0.98). Cystatin C achieved 100% specificity at the optimal cut-off for severe CKD and showed comparable diagnostic accuracy to creatinine under the eGFRcr-cys framework (AUC 0.978 vs. 0.957). β2M demonstrated AUCs up to 0.97, with sensitivity and specificity above 90%. These findings support a multi-marker evaluation within the 2021 CKD-EPI-based staging, rather than validation against measured GFR. Larger studies incorporating measured GFR and relevant clinical confounders are warranted.
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