Albuminuria Predicts a Rapid Decline in Kidney Function in 2 International, Longitudinal Cohorts of Adults With Sickle Cell Anemia

Chronic kidney disease (CKD) is common and a major contributor to increased morbidity and early mortality in people with sickle cell anemia (SCA). Urine albumin-to-creatinine ratio (uACR) is recommended to identify patients with SCA-related CKD but its utility in predicting long-term kidney dysfunction remains unclear in this patient population. In two independent, longitudinal cohorts of patients with hemoglobin SS or Sβ⁰-thalassemia (USA: n = 268, median follow-up 6 years; France: n = 310, median follow-up 8.2 years) we investigated the utility of uACR, as well as other clinical and modifiable risk factors, for predicting a decline in kidney function as determined by the rate of estimated glomerular filtration rate (eGFR) decline. Using linear mixed-effects models, a higher baseline uACR independently predicted a faster rate of eGFR decline as well as a more rapid annual eGFR decline, defined as ≥ 3 mL/min/1.73m² (p ≤ 0.009). Furthermore, baseline uACR of ≥ 100 mg/g creatinine was independently associated with the rate of eGFR decline and rapid annual eGFR decline in both cohorts. Tobacco smoking was also associated with a faster rate of eGFR decline and was congruous between the two cohorts. In conclusion, we demonstrate that uACR is an important clinical tool that predicts a more rapid decline in kidney function and should be routinely monitored in people with SCA. Our data also support preventative care to reduce tobacco smoking for mitigating the risk of CKD progression in this high-risk population.