Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study.
<h4>Background</h4> <p>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.</p> <h4>Methods</h4&...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
BioMed Central
2017
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| _version_ | 1826263710542331904 |
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| author | Plewes, K Kingston, H Ghose, A Maude, R Herdman, M Leopold, S Ishioka, H Hasan, M Haider, M Alam, S Piera, K Charunwatthana, P Silamut, K Yeo, T Faiz, M Lee, S Mukaka, M Turner, G Anstey, N Jackson Roberts, L White, N Day, N Hossain, M Dondorp, A |
| author_facet | Plewes, K Kingston, H Ghose, A Maude, R Herdman, M Leopold, S Ishioka, H Hasan, M Haider, M Alam, S Piera, K Charunwatthana, P Silamut, K Yeo, T Faiz, M Lee, S Mukaka, M Turner, G Anstey, N Jackson Roberts, L White, N Day, N Hossain, M Dondorp, A |
| author_sort | Plewes, K |
| collection | OXFORD |
| description | <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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.</p> <h4>Conclusions</h4> <p>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.</p> |
| first_indexed | 2024-03-06T19:56:09Z |
| format | Journal article |
| id | oxford-uuid:25a8349f-8f5a-4f65-a25d-2b6a60789f8b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:56:09Z |
| publishDate | 2017 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | oxford-uuid:25a8349f-8f5a-4f65-a25d-2b6a60789f8b2022-03-26T11:56:49ZCell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:25a8349f-8f5a-4f65-a25d-2b6a60789f8bEnglishSymplectic Elements at OxfordBioMed Central2017Plewes, KKingston, HGhose, AMaude, RHerdman, MLeopold, SIshioka, HHasan, MHaider, MAlam, SPiera, KCharunwatthana, PSilamut, KYeo, TFaiz, MLee, SMukaka, MTurner, GAnstey, NJackson Roberts, LWhite, NDay, NHossain, MDondorp, A <h4>Background</h4> <p>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.</p> <h4>Methods</h4> <p>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.</p> <h4>Results</h4> <p>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.</p> <h4>Conclusions</h4> <p>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.</p> |
| spellingShingle | Plewes, K Kingston, H Ghose, A Maude, R Herdman, M Leopold, S Ishioka, H Hasan, M Haider, M Alam, S Piera, K Charunwatthana, P Silamut, K Yeo, T Faiz, M Lee, S Mukaka, M Turner, G Anstey, N Jackson Roberts, L White, N Day, N Hossain, M Dondorp, A Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study. |
| title | Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study. |
| title_full | Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study. |
| title_fullStr | Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study. |
| title_full_unstemmed | Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study. |
| title_short | Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study. |
| title_sort | cell free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria an observational study |
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