Acute Kidney Injury During Sickle Cell Crisis

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Project Summary/Abstract: Sickle cell disease (SCD) patients suffer from repeated episodes of vaso-occlusive pain crisis and acute chest syndrome, yet data is lacking on the impact of these clinical events on progressive end-organ damage, including kidney injury. Cell free heme and hemoglobin can be elevated during these hemolytic events. Murine models suggest that an acute increase in cell free heme and hemoglobin from a hemolytic event will mediate kidney injury. As it is well recognized the patients with sickle cell suffer from a higher prevalence of developing kidney injury, it is vital to conduct research to determine the impact of hemolysis during acute SCD crisis (pain crisis or acute chest syndrome) on the development of kidney injury. We hypothesize that during SCD crisis, kidney injury occurs and is associated with elevations in cell free heme/hemoglobin and endothelin- 1 levels. Methodology and Aims: Patients with HbSS and SB0 thalassemia (ages 6-20) admitted for SCD crisis (pain crisis or acute chest syndrome) will consent to daily first morning urine and blood collection. Urine samples will be measured for acute kidney injury biomarkers and blood will be measured for cell free heme, hemoglobin, and endothelin-1. To understand the epidemiology of SCD crisis associated AKI, we will determine the frequency of AKI as defined by the KDIGO definition (rise in serum creatinine of 0.3mg/dL or 50% from baseline, or decrease in urine output). We will perform analysis of potential risk factors for kidney injury including changes in blood counts from baseline and administration of NSAIDs or other nephrotoxic medications. Second, we still study the pathophysiology of kidney injury during SCD crisis. We will determine the associations between elevations in cell free heme/hemoglobin and endothelin-1 with the development of clinical AKI (defined by KDIGO) or subclinical AKI (elevation in urinary biomarkers without a rise in serum creatinine). Expected results: At the completion of this R03 proposal, we will establish an association linking hemolysis during SCD with the development of kidney injury. As sickle cell patients are at increased risk for mortality from chronic kidney disease, it is imperative to better understand the impact of repeated sickle cell crisis on kidney injury so that diagnostic, therapeutic, and supportive care protocols for monitoring and preventing AKI during SCD crisis can be developed.