Chronic kidney disease (CKD) has a significant impact on sickle cell disease (SCD) morbidity and mortality. Early identification of individuals at highest risk of developing CKD may allow therapeutic intervention to prevent worse outcomes. This study aimed to evaluate the prevalence and risk factor for CKD among adults with SCD in Brazil.

Participants in the REDS-III multicenter SCD cohort with more severe genotypes [sickle cell anemia (SCA) = hemoglobin (Hb) SS, Hb Sβ0-thalassemia, Hb Sβ+-thalassemia with mutations associated with severe phenotype] aged ≥18 years at time of enrollment with at least two serum creatinine values were analyzed. Participants were enrolled between 2013-2015 and were prospectively followed and monitored for the occurrence of clinical complication, including death, for up to three years. The estimated glomerular filtration rate (eGFR) was calculated using the JSCCS-GFR Equation. The CKD stage was defined according to the K/DOQI. For participants with multiple eGFR measures, we use the two most recent values to define CKD; for those who presented different CKD stages, we used the mean value to define the outcome. Because albuminuria status was not known in all participants, those with CKD stage 2 or higher were compared to those with eGFR≥90. The association among the characteristics and the presence of CKD stage 2 or higher were assessed using binary logistic regression model.

497 (65.7%) participants were receiving hydroxyurea (HU) therapy, 105 (13.9%) were treated with chronic blood transfusion (CBT), and 69 (9.1%) were under both therapies. Among the 756 participants, 569 (75.3%) had eGFR≥90, 175 (23.1%) had stage-2, six (0.79%) had stage-3, and six (0.79%) had ESRD. Participants with CKD stage 2 or higher were significantly older and predominantly male when compared with those with eGFR≥90. There was no association between CKD stage 2 or higher and HU or CBT. Participants with CKD stage 2 or higher had a 2.3 (95%CI: 1.4–3.7) times higher odds for death when compared to those with eGFR≥90. Male sex (OR: 34.7; 95%CI: 20.3–62.5), higher age (OR: 1.03; 95%CI: 1.01–1.05), higher diastolic blood pressure (OR: 1.03; 95%CI: 1.002–1.05), lower Hb (OR: 0.704; 95%CI: 0.59–0.83), and lower reticulocytes (OR: 0.91; 95%CI: 0.86–0.96) levels were significantly associated with stage 2 or higher in the final multivariate model.

We observed a higher odds for mortality in participants with CKD stage 2 or higher when compared to those with eGFR≥90. This highlights the importance of early detection and implementation of preventative therapies. We also observed a significant independent association between lower levels of Hb and reticulocytes with CKD stage 2 or higher. These data might reflect a state of hypoproliferative anemia in participants with CKD stage 2 or higher likely due to deficiency of erythropoietin. In this study, CKD stage 2 or higher was more prevalent in men than in women, and male sex was the strongest independent predictor of CKD stage 2 or higher in the final model. This finding might be used to target individuals at highest risk for CKD in prevention campaigns.

CKD stage 2 or higher was observed in one-quarter of adults with SCA. Older age, male sex, higher diastolic blood pressure, lower hemoglobin, and lower reticulocytes levels were significantly associated with occurrence of CKD stage 2 or higher, which, in turn, significantly increased the risk of mortality.