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https://hdl.handle.net/10356/85197
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DC Field | Value | Language |
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dc.contributor.author | Plewes, Katherine | en |
dc.contributor.author | Kingston, Hugh W.F. | en |
dc.contributor.author | Ghose, Aniruddha | en |
dc.contributor.author | Maude, Richard J. | en |
dc.contributor.author | Herdman, M. Trent | en |
dc.contributor.author | Leopold, Stije J. | en |
dc.contributor.author | Ishioka, Haruhiko | en |
dc.contributor.author | Hasan, Md. Mahtab Uddin | en |
dc.contributor.author | Haider, Md. Shafiul | en |
dc.contributor.author | Alam, Shamsul | en |
dc.contributor.author | Piera, Kim A. | en |
dc.contributor.author | Charunwatthana, Prakaykaew | en |
dc.contributor.author | Silamut, Kamolrat | en |
dc.contributor.author | Yeo, Tsin Wen | en |
dc.contributor.author | Faiz, Md. Abul | en |
dc.contributor.author | Lee, Sue J. | en |
dc.contributor.author | Mukaka, Mavuto | en |
dc.contributor.author | Turner, Gareth D. H. | en |
dc.contributor.author | Anstey, Nicholas M. | en |
dc.contributor.author | Jackson Roberts II, L. | en |
dc.contributor.author | White, Nicholas J. | en |
dc.contributor.author | Day, Nicholas P. J. | en |
dc.contributor.author | Hossain, Md. Amir | en |
dc.contributor.author | Dondorp, Arjen M. | en |
dc.date.accessioned | 2017-09-04T08:11:06Z | en |
dc.date.accessioned | 2019-12-06T15:59:16Z | - |
dc.date.available | 2017-09-04T08:11:06Z | en |
dc.date.available | 2019-12-06T15:59:16Z | - |
dc.date.issued | 2017 | en |
dc.identifier.citation | 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-. | en |
dc.identifier.uri | https://hdl.handle.net/10356/85197 | - |
dc.description.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. | en |
dc.format.extent | 12 p. | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | BMC Infectious Diseases | en |
dc.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. | en |
dc.subject | Acute kidney injury | en |
dc.subject | Pathophysiology | en |
dc.title | Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study | en |
dc.type | Journal Article | en |
dc.contributor.school | Lee Kong Chian School of Medicine (LKCMedicine) | en |
dc.identifier.doi | 10.1186/s12879-017-2373-1 | en |
dc.description.version | Published version | en |
item.fulltext | With Fulltext | - |
item.grantfulltext | open | - |
Appears in Collections: | LKCMedicine Journal Articles |
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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.pdf | 702.9 kB | Adobe PDF | View/Open |
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