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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 F; Ghose, Aniruddha; Maude, Richard J; Herdman, M Trent; Leopold, Stije J; Ishioka, Haruhiko; Hasan, Md Mahtab Uddin; Haider, Md Shafiul; Alam, Shamsul; Piera, Kim A; Charunwatthana, Prakaykaew; Silamut, Kamolrat; Yeo, Tsin W; Faiz, Md Abul; Lee, Sue J; Mukaka, Mavuto; Turner, Gareth D H; Anstey, Nicholas M; Jackson Roberts, L; White, Nicholas J; Day, Nicholas P J; Hossain, Md Amir; Dondorp, Arjen M.
Afiliação
  • Plewes K; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Kingston HWF; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Ghose A; Department of Medicine and Vancouver Coastal Health, University of British Columbia Clinical Investigator program, Vancouver, Canada.
  • Maude RJ; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Herdman MT; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Leopold SJ; Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
  • Ishioka H; Department of Medicine, Chittagong Medical College and Hospital, Chittagong, Bangladesh.
  • Hasan MMU; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Haider MS; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Alam S; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Piera KA; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Charunwatthana P; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Silamut K; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Yeo TW; Department of Medicine, Chittagong Medical College and Hospital, Chittagong, Bangladesh.
  • Faiz MA; Department of Nephrology, Chittagong Medical College and Hospital, Chittagong, Bangladesh.
  • Lee SJ; Department of Anesthesiology, Chittagong Medical College and Hospital, Chittagong, Bangladesh.
  • Mukaka M; Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
  • Turner GDH; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Anstey NM; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Jackson Roberts L; Global Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia.
  • White NJ; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
  • Day NPJ; Dev Care Foundation, Dhaka, Bangladesh.
  • Hossain MA; Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
  • Dondorp AM; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
BMC Infect Dis ; 17(1): 313, 2017 04 27.
Article em En | MEDLINE | ID: mdl-28449641
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 < 0.001; IsoFs: 41.7 pg/ml; 95% CI, 30.2-57.6 pg/ml; P < 0.001). Cell-free hemoglobin correlated with markers of hemolysis, parasite burden (P. falciparum histidine rich protein 2 (PfHRP2)), and F2-IsoPs. Plasma F2-IsoPs and IsoFs inversely correlated with pH, positively correlated with creatinine, PfHRP2 and fractional excretion of sodium, and were higher in patients later requiring hemodialysis. Plasma F2-IsoP concentrations also inversely correlated with red cell deformability and were higher in fatal cases. Mixed effects modeling including an interaction term for CFH and time showed that F2-IsoPs, IsoFs, PfHRP2, CFH, and red cell rigidity were independently associated with increasing creatinine over 72 h. Multivariable logistic regression showed that admission F2-IsoPs, IsoFs and red cell deformability were associated with the need for subsequent hemodialysis. CONCLUSIONS: Cell-free hemoglobin and lipid peroxidation are associated with acute kidney injury and disease severity in falciparum malaria, suggesting a pathophysiological role in renal tubular injury. Evaluation of adjunctive therapies targeting cell-free hemoglobin-mediated oxidative stress is warranted.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hemoglobinas / Malária Falciparum / Estresse Oxidativo / Injúria Renal Aguda Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Hemoglobinas / Malária Falciparum / Estresse Oxidativo / Injúria Renal Aguda Tipo de estudo: Etiology_studies / Observational_studies / Risk_factors_studies Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2017 Tipo de documento: Article