Performance of Estimated Glomerular Filtration Rate Equations in Sickle Cell Anemia

Background: Estimated Glomerular filtration rate (GFR) is used to diagnose and stratify kidney disease, with the Chronic Kidney Disease-Epidemiology Collaboration 2021 (CKD-EPI 2021) and European Kidney Function Consortium equations (EKFC) validated across worldwide populations. Although CKD frequently occurs in sickle cell anemia (SCA), the performance of these equations is unknown. We aimed to determine the accuracy and precision of these equations compared to measured GFR (mGFR) in a SCA cohort. Methods: Participants with SCA, aged 29 to 39 years, with no red cell transfusion or acute illness within one month, were included. All had serum cystatin-C, creatinine, albuminuria testing, and mGFR performed using a 99m-Tc DTPA renal scan. eGFR was calculated using the EKFC, CKD-EPI 2021, CKD-EPI 2012 cystatin, and creatinine equations. CKD was defined using the KDIGO definition. The Bland-Altman limit of agreement method was used to assess the agreement between mGFR and eGFR. Accuracy of all estimating equations was evaluated by determining the percentage of eGFR lying within 30% (P30) of the mGFR. Results: Of 99 persons, 56.7%(56) were women, mean mGFR ± SD was 94.5 ± 21.2 mL/min/1.73 m2; 65% (64) had CKD. The EKFC-creat equation had the highest accuracy, P30: 66.7%, while CKD-EPI 2021 creat-cyst had the lowest, P30: 49.5%. CKD-EPI-creat-cyst-2021 had the highest precision (SD of difference: 26.2), while the EKFC-creat-cyst equation had the lowest (SD of the difference: 19.8).(see Figure 1) These equations performed better than the CKD-EPI 2012 cystatin and creatinine equations (p30: 46.4 and 27.7% respectively) Conclusion: Newer GFR estimating equations perform poorly in SCA, with the EFKC-creatinine equation having the best accuracy and precision. Future studies should derive and validate estimating GFR equations in SCA populations. Funding: Government Support – Non-U.S.Figure 1: Limits of Agreement Plots. Measured Glomerular Filtration rate versus (a) CKD-EPI 2021-creatinine equation (b) CKD-EPI-2021 creatinine cystatin-C (c) EKFC creatinine-equation (d) EKFC cystatin-C equation (e) EKFC creatinine-cystatin-C equation