UBC Faculty Research and Publications

Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study Plewes, Katherine; Kingston, Hugh W; Ghose, Aniruddha; Maude, Richard J; Herdman, M. T; Leopold, Stije J; Ishioka, Haruhiko; Hasan, Md. M U; Haider, Md. S; Alam, Shamsul; Piera, Kim A; Charunwatthana, Prakaykaew; Silamut, Kamolrat; Yeo, Tsin W; Faiz, Md. A; Lee, Sue J; Mukaka, Mavuto; Turner, Gareth D; Anstey, Nicholas M; Jackson Roberts, L.; White, Nicholas J; Day, Nicholas P; Hossain, Md. A; Dondorp, Arjen M

Abstract

Background Intravascular hemolysis is an intrinsic feature of severe malaria pathophysiology but the pathogenic role of cell-free hemoglobin-mediated oxidative stress in severe malaria associated acute kidney injury (AKI) is unknown. Methods As part of a prospective observational study, enrolment plasma cell-free hemoglobin (CFH), lipid peroxidation markers (F₂-isoprostanes (F₂-IsoPs) and isofurans (IsoFs)), red cell deformability, and serum creatinine were quantified in Bangladeshi patients with severe falciparum malaria (n = 107), uncomplicated malaria (n = 80) and sepsis (n = 28). The relationships between these indices and kidney function and clinical outcomes were examined. Results AKI was diagnosed at enrolment in 58% (62/107) of consecutive patients with severe malaria, defined by an increase in creatinine ≥1.5 times expected baseline. Severe malaria patients with AKI had significantly higher plasma cell-free hemoglobin (geometric mean CFH: 8.8 μM; 95% CI, 6.2–12.3 μM), F₂-isoprostane (56.7 pg/ml; 95% CI, 45.3–71.0 pg/ml) and isofuran (109.2 pg/ml; 95% CI, 85.1–140.1 pg/ml) concentrations on enrolment compared to those without AKI (CFH: 5.1 μM; 95% CI, 4.0–6.6 μM; P = 0.018; F2-IsoPs: 27.8 pg/ml; 95% CI, 23.7–32.7 pg/ml; P 

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