Background Sickle cell trait and sickle cell disease are thought to be independent risk factors for CKD, but the trajectory and predictors of kidney function decline in patients with these phenotypes are not well understood. Methods Our multicenter, observational study used registry data (collected January 2005 through June 2018) and included adult black patients with sickle cell trait or disease (exposures) or normal hemoglobin phenotype (reference) status (ascertained by electrophoresis) and at least 1 year of follow-up and three eGFR values.We used linearmixedmodels to evaluate the difference in themean change in eGFR per year. Results We identified 1251 patients with sickle cell trait, 230 with sickle cell disease, and 8729 reference patients, with a median follow-up of 8 years. After adjustment, eGFR declined significantly faster in patients with sickle cell trait or sickle cell disease compared with reference patients; it also declined significantly faster in patients with sickle cell disease than in patients with sickle cell trait. Male sex, diabetes mellitus, and baseline eGFR $90 ml/min per 1.73 m2 were associated with faster eGFR decline for both phenotypes. In sickle cell trait, low hemoglobin S and elevated hemoglobin A were associated with faster eGFR decline, but elevated hemoglobins F and A2 were renoprotective. Conclusions Sickle cell trait and disease are associated with faster eGFR decline in black patients, with faster decline in sickle cell disease. Lowhemoglobin Swas associated with faster eGFR decline in sickle cell trait but may be confounded by concurrent hemoglobinopathies. Prospective andmechanistic studies are needed to develop best practices to attenuate eGFR decline in such patients.
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