Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/85197
Title: Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study
Authors: 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 Wen
Faiz, Md. Abul
Lee, Sue J.
Mukaka, Mavuto
Turner, Gareth D. H.
Anstey, Nicholas M.
Jackson Roberts II, L.
White, Nicholas J.
Day, Nicholas P. J.
Hossain, Md. Amir
Dondorp, Arjen M.
Keywords: Acute kidney injury
Pathophysiology
Issue Date: 2017
Source: Plewes, K., Kingston, H. W. F., Ghose, A., Maude, R. J., Herdman, M. T., Leopold, S. J., et al. (2017). Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study. BMC Infectious Diseases, 17, 313-.
Series/Report no.: BMC Infectious Diseases
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 < 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.
URI: https://hdl.handle.net/10356/85197
http://hdl.handle.net/10220/43680
DOI: 10.1186/s12879-017-2373-1
Rights: © 2017 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

SCOPUSTM   
Citations 20

24
checked on Sep 3, 2020

WEB OF SCIENCETM
Citations 50

26
checked on Oct 14, 2020

Page view(s) 50

225
checked on Oct 19, 2020

Download(s) 50

43
checked on Oct 19, 2020

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.