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Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming

BACKGROUND: Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1–10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the de...

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Autores principales: Wijewickrama, Eranga Sanjeewa, Mohamed, Fahim, Gawarammana, Indika B., Endre, Zoltan H., Buckley, Nicholas A., Isbister, Geoffrey K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675918/
https://www.ncbi.nlm.nih.gov/pubmed/34871314
http://dx.doi.org/10.1371/journal.pntd.0010011
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author Wijewickrama, Eranga Sanjeewa
Mohamed, Fahim
Gawarammana, Indika B.
Endre, Zoltan H.
Buckley, Nicholas A.
Isbister, Geoffrey K.
author_facet Wijewickrama, Eranga Sanjeewa
Mohamed, Fahim
Gawarammana, Indika B.
Endre, Zoltan H.
Buckley, Nicholas A.
Isbister, Geoffrey K.
author_sort Wijewickrama, Eranga Sanjeewa
collection PubMed
description BACKGROUND: Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1–10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites. METHODS: We conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), β2-microglobulin (uβ2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming. RESULTS: There were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1–2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0–4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85–1.0) and no biomarker performed better than sCr at later time points. CONCLUSIONS: sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.
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spelling pubmed-86759182021-12-17 Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming Wijewickrama, Eranga Sanjeewa Mohamed, Fahim Gawarammana, Indika B. Endre, Zoltan H. Buckley, Nicholas A. Isbister, Geoffrey K. PLoS Negl Trop Dis Research Article BACKGROUND: Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1–10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites. METHODS: We conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), β2-microglobulin (uβ2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming. RESULTS: There were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1–2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0–4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85–1.0) and no biomarker performed better than sCr at later time points. CONCLUSIONS: sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming. Public Library of Science 2021-12-06 /pmc/articles/PMC8675918/ /pubmed/34871314 http://dx.doi.org/10.1371/journal.pntd.0010011 Text en © 2021 Wijewickrama et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wijewickrama, Eranga Sanjeewa
Mohamed, Fahim
Gawarammana, Indika B.
Endre, Zoltan H.
Buckley, Nicholas A.
Isbister, Geoffrey K.
Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming
title Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming
title_full Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming
title_fullStr Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming
title_full_unstemmed Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming
title_short Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming
title_sort serum and urinary biomarkers for early detection of acute kidney injury following hypnale spp. envenoming
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675918/
https://www.ncbi.nlm.nih.gov/pubmed/34871314
http://dx.doi.org/10.1371/journal.pntd.0010011
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