Serial serum creatinine, SDMA and urinary acute kidney injury biomarker measurements in dogs envenomated by the European adder (Vipera berus)

Hannah J Harjen,Kristin P Anfinsen,Elena R Moldal,Bente K Sævik,Karin E Zimmer,Tove V Nicolaysen,Hege Lund,Runa Rørtveit,Tale Negard

doi:10.1186/s12917-021-02851-8

Abstract

BackgroundAcute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Snake envenomation is one of several causes of AKI in dogs and humans. Dogs are commonly envenomated by the European adder (Vipera berus) between April and October each year, but few studies exist examining serial serum creatinine (sCr) and symmetric dimethylarginine (SDMA) measurements and AKI biomarkers in these dogs. Novel urinary biomarkers could improve clinical outcome by allowing earlier diagnosis of and intervention in AKI. The aim of this study was to assess the presence of AKI in dogs envenomated by V. berus at 12, 24 and 36 h after bite, as well as 14 days later, using sCr, SDMA and a panel of urinary AKI biomarkers normalised to urine creatinine (uCr), compared to a group of healthy control dogs.ResultsThirty-five envenomated dogs and 35 control dogs were included. Serum creatinine did not exceed the upper reference limit at any time point in any dog after envenomation. Serum SDMA did not exceed 0.89 μmol/L in any dog. Compared to controls, urinary albumin/uCr, neutrophil gelatinase-associated lipocalin/uCr and monocyte chemotactic protein-1/uCr were significantly elevated 12 h (P < 0.0001, P < 0.0001, P = 0.01), 24 h (P < 0.001, P < 0.001, P = 0.002) and 36 h (P < 0.001, P < 0.001, P = 0.0008) after bite. Osteopontin/uCr was higher 24 and 36 h after bite (P < 0.0001), kidney injury molecule-1/uCr, interleukin-8/uCr and γ- glutamyl transferase/uCr were significantly higher 36 h after bite (P = 0.003, P = 0.0005, P = 0.001). Urinary cystatin C/uCr was not significantly different to controls at any timepoint. Biomarker/uCr ratios were not significantly different 14 days after envenomation compared to controls.ConclusionUrinary biomarker/Cr ratios are indicative of mild transient, non-azotaemic AKI in dogs envenomated by V. berus.

Highlights

Acute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury
Twenty-two cases presented to the small animal hospital at the Norwegian University of Life Sciences (NMBU), three cases to Anicura Dyresykehus Oslo (ADO), six cases to Evidensia Oslo Dyresykehus (EOD) and four cases to Anicura Jeløy Dyresykehus (AJD)
Increases in the urinary AKI biomarkers Kidney injury molecule-1 (KIM-1), GGT, neutrophil gelatinaseassociated lipocalin (NGAL), interleukin 8 (IL-8), OPN, MCP-1 and albumin were indicative of renal tubular injury in dogs 12–36 h after envenomation by V.berus in this study, further work is needed to ascertain the specificity of IL-8, NGAL, OPN and MCP-1

Summary

Introduction

Acute kidney injury (AKI) is associated with high morbidity and mortality in dogs, but diagnosis may be impaired due the insensitivity of routine renal function biomarkers to detect earlier or milder forms of injury. Studies to date have failed to show elevations in renal function markers such as serum creatinine (sCr) after V.berus envenomation, but measurements of urinary markers of AKI and histopathological findings are indicative of tubular injury in these dogs [5, 8, 9]. These studies are limited, and AKI in dogs envenomated by V. berus warrants further investigation. V.berus envenomated dogs could represent a model for studying kidney injury biomarkers in the early phase of AKI

Objectives

Methods

Results

Discussion

Conclusion