Comparative Assessment of Creatinine-Based eGFR and Cystatin C-Based eGFR in Sickle Cell Disease

Background: Accurate estimated glomerular filtration rate (eGFR) is essential in sickle cell disease (SCD), a condition in which patients are at risk for both hyperfiltration and progressive kidney injury. Creatinine-based eGFR (eGFR-Cr) may be unreliable in SCD due to reduced muscle mass, while cystatin C-based eGFR (eGFR-Cys) offers a muscle-mass–independent alternative. This study compares eGFR-Cr and c eGFR-Cys in patients with SCD to assess their agreement and clinical relevance. Methods: We conducted a cross-sectional study of patients with SCD followed at a quaternary hospital between Sept/2024 and April/2025. eGFR was calculated using the CKD-EPI 2021 creatinine and CKD-EPI 2012 cystatin C equations on the same blood sample. Hyperfiltration was defined as GFR >140 for men and >130 for women. Comparisons between methods were assessed using the Mann-Whitney test and Bland-Altman analysis. Results: We analyzed 45 patients with a median age of 35 (18-74) years, 69% female, 93% black. At study entry, 68.9% were using hydroxyurea, 15.5% Renin-Angiotensin system inhibitors, and no one was diagnosed with diabetes. 18.6% of patients were underweight, 55.8% had a normal BMI, and 25.6% were overweight. Median eGFR-Cr eGFR-Cys were 124 (IQR 105-133) mL/min/1.73m2 and 101 (IQR 69-118) mL/min/1.73m2, respectively (p <0.001). The Bland-Altman analysis is shown in Figure 1. The eGFR-Cr equation identified significantly more hyperfiltration cases than eGFR-Cyst equation (26.7% vs 8.9%, p <0.001). Microalbuminuria was found in 22% of cases, and macroalbuminuria in 13%. eGFR calculated by either Cr (R = -283, P=0.062) or Cyst (R = -107, P=0.490) was not significantly correlated with albuminuria. Conclusion: Among patients with SCD, eGFR-Cr was significantly higher than eGFR-Cys, possibly overestimating the diagnosis of hyperfiltration. Cystatin C may be more accurate for eGFR assessment in SCD.