Chronic kidney disease in adults with sickle cell trait: A systematic review and meta-analysis

Sickle cell trait (SCT) may increase the risk of chronic kidney disease (CKD). We aim to determine the pooled statistics of the association between SCT and CKD. Studies published up to May 2024 on PubMed, Embase, Global Health Library, and Web of Science were screened. We included studies reporting odds ratios (OR) or hazard ratios (HR) of CKD and/or end-stage renal disease (ESRD) comparing adults with and without SCT. The risk of bias was evaluated using the ROBINS-E tool. The pooled SCT prevalence was calculated among patients with CKD/ESRD. Random-effects analysis was performed. Only studies with low or some concerns of bias were included, corresponding to 18,847 SCT participants and 1,060,818 without SCT. SCT participants had higher odds of having an eGFR ≤ 60 ml/min/1.73 m² (OR: 1.62, 95% CI: 1.39-1.89), proteinuria (OR: 2.02, 95% CI: 1.61-2.54), and eGFR ≤ 60 ml/min/1.73 m² and/or proteinuria (OR: 1.79, 95% CI: 1.44-2.22). The pooled prevalence of SCT among African Americans with ESRD was 10% (95% CI: 8-12%); however, heterogeneity was very high (I²: 85.6%). There was a higher HR for ESRD (p = 0.04) in the studies that included both males and females (HR: 1.72, 95% CI: 1.13-2.61) compared to the study that included only females (HR: 0.75, 95% CI: 0.39 - 1.44), suggesting that males have a higher risk of ESRD. Controversial results were observed for the association of CKD with hypertension and diabetes. SCT increases the risk of developing CKD and ESRD. PROSPERO registration: CRD42021275274.