Anthony Batte, MMed, MBChB
Nominated From: Indiana University
Research Site: Mulago Hospital
Research Area: Kidney disease in sickle cell anemia
Primary Mentor: Chandy John
Biomarkers of acute kidney injury in children with sickle cell anemia and vaso-occlusive crisis
Globally about 300,000 children are born with sickle cell anemia (SCA) annually with 80% of the affected children born in Africa. In Uganda, an estimated 15,000 children are born with SCA each year and approximately 70-80% of these children with SCA will die before reaching five years of age. Vaso-occlusive pain crises (VOC) are a common complication in children with SCA and a risk factor for acute kidney injury (AKI); with the incidence of AKI ranging from 2.3% in uncomplicated painful crisis to 13.0% in children with severe acute chest syndrome. AKI is defined by reduced urine output or increases in serum creatinine. However, creatinine is affected by factors such as age and nutritional status. Further, glomerular hyperfiltration in SCA reduces creatinine levels and limits detection of AKI. These limitations highlight the need for biomarkers to improve early detection of AKI in SCA.
Biomarkers can provide insight into etiology, and pathophysiology of AKI. For example, biomarkers can differentiate between reduced glomerular filtration (Creatinine, Cystatin C) and tubulointerstitial injury (neutrophil gelatinase-associated lipocalin(NGAL), and kidney injury molecule 1 (KIM-1). There is urgent need to explore how AKI biomarkers perform in children with SCA, and to evaluate pathophysiology of AKI associated with VOC. During vaso-occlusive SCA episodes, nitric oxide bioavailability can be quenched by increases in cell-free hemoglobin contributing to microvascular dysfunction. Impaired nitric oxide bioavailability is a risk factor for AKI following cardiopulmonary bypass, and increased cell-free hemoglobin during cardiac surgery is a risk factor for development of AKI. There is evidence that iron scavengers, e.g. haptoglobin, may have a renal protective role during acute hemolytic episodes. We hypothesize that increased plasma levels of cell-free hemoglobin and reduced haptoglobin may contribute to AKI in children with SCA during VOCs. Further, we hypothesize novel AKI biomarkers may improve our ability to detect AKI in a population of children where creatinine-based diagnosis of AKI is problematic.
Renal disease contributes to significant morbidity and mortality in children with SCA, and new tools to identify AKI are urgently needed. There are limited data on alternative biomarkers of AKI in children with SCA, and the results from this study will determine whether these biomarkers are promising candidates to improve AKI diagnosis. Further, data on cell-free hemoglobin and haptoglobin will be useful in understanding the pathophysiology of AKI in children with SCA and may lead to potential therapeutics
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