Improving Scientific Rigor of Renal Clinical Endpoints for Sickle Cell Anemia

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Project Summary/Abstract The parent R01 will develop and validate a novel eGFR equation and measure changes in GFR over one year. Individuals with sickle cell anemia (SCA) are at an increased risk for the development of venous thromboembolism (VTE). This risk likely increases further in the setting of progressive kidney disease. In addition, thrombotic events may hasten the progression to end- stage renal disease in individuals SCA. Prospective studies are need to examine the tri-directional associations between SCA, chronic kidney disease, and thrombotic events. This proposal will prospectively examine the prevalence of VTE in 200 pediatric and 200 adult participants with SCA at baseline and the incidence of new and recurrent VTE at one year. This data will provide prospective evidence to support prior cohort data suggesting a 10-20% one-year recurrence rate for VTE in those with SCA who have had a first thrombotic event. Next, this proposal will characterize the current treatment approaches to secondary thrombosis at baseline and adherence to secondary thromboprophylaxis treatment at one year. The current ASH Sickle Cell Guidelines were unable to provide strong recommendations due to the lack of solid evidence in the field. Finally, the proposal will measure the trajectory of GFR changes in participants with and without a history of thrombosis. Exploratory analysis will also compare the trajectory for participants with a new thrombotic event during the study period. This data is vital to determine whether a history of thrombotic events should be included in the stratification of renal outcomes for future studies of renoprotective agents in SCA. Each of these aims will provide vital preliminary data to support a feasibility trial of anticoagulation in individuals with SCA who have a history of thrombotic events as well as broader trials in children with VTE and persistent thrombotic risk factors.