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

Eranga Sanjeewa Wijewickrama,Fahim Mohamed,Zoltan H Endre,Nicholas A Buckley,Geoffrey K Isbister,Indika B Gawarammana,Ana M Moura-Da-Silva

doi:10.1371/journal.pntd.0010011

Abstract

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. 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. 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. sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming.

Highlights

Snakebite is a major public health problem and snake envenoming is associated with considerable morbidity and mortality worldwide, in Asia and Africa.[1,2] There are five medically important venomous snakes in Sri Lanka, Russell’s viper (Daboia russelii), common krait (Bungarus caeruleus), Indian cobra (Naja naja), saw-scaled viper (Echis carinatus) and the hump-nosed pit viper (HNV; Hypnale spp.)
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. serum cystatin C (sCysC) performed the best at 0–4 h post-bite in predicting moderate to severe Acute kidney injury (AKI) (AUC-ROC 0.95;95%CI:0.85–1.0) and no biomarker performed better than serum creatinine (sCr) at later time points
Conclusions sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following Hump-nosed pit viper (HNV) envenoming

Summary

Introduction

Snakebite is a major public health problem and snake envenoming is associated with considerable morbidity and mortality worldwide, in Asia and Africa.[1,2] There are five medically important venomous snakes in Sri Lanka, Russell’s viper (Daboia russelii), common krait (Bungarus caeruleus), Indian cobra (Naja naja), saw-scaled viper (Echis carinatus) and the hump-nosed pit viper (HNV; Hypnale spp.). HNV bites account for the majority of venomous snakebites in Sri Lanka, similar to much of India, but severe systemic envenoming occurs in only a small proportion. 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

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Conclusion