Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs

Jennifer Davis; Gabriele Rossi; Rachel E Cianciolo; Kwok M Ho; Giselle L Hosgood; David W Miller; Anthea L Raisis

doi:10.1016/j.vaa.2022.02.006

Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs

Vet Anaesth Analg. 2022 Jul;49(4):344-353. doi: 10.1016/j.vaa.2022.02.006. Epub 2022 Mar 9.

Authors

Jennifer Davis¹, Gabriele Rossi², Rachel E Cianciolo³, Kwok M Ho⁴, Giselle L Hosgood², David W Miller², Anthea L Raisis²

Affiliations

¹ School of Veterinary Medicine, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, Western Australia, Australia. Electronic address: jen@vetanaesthesiatips.com.
² School of Veterinary Medicine, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, Western Australia, Australia.
³ Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA.
⁴ School of Veterinary Medicine, College of Science, Health, Engineering and Education, Murdoch University, Murdoch, Western Australia, Australia; Department of Intensive Care Medicine, Royal Perth Hospital, Perth, Western Australia, Australia; Medical School, University of Western Australia, Perth, Western Australia, Australia.

PMID: 35490089
DOI: 10.1016/j.vaa.2022.02.006

Abstract

Objectives: To document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs.

Study design: Experimental, repeated measures, prospective study.

Animals: A group of six male adult Greyhound dogs.

Methods: Following general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett's adjustment, p < 0.05.

Results: Structural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1-25.9) ng mL^-1 NGAL (p = 0.002), 2.54 (1.64-3.43) mg mL^-1 CysC (p = 0.009) and 2043 (790-5458) U L^-1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein-creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage.

Conclusions and clinical relevance: Urinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.

Keywords: biomarkers; canine; cystatin C; gamma-glutamyl transferase; ischaemia-reperfusion injury; neutrophil gelatinase-associated lipocalin.

MeSH terms

Acute Kidney Injury* / diagnosis
Acute Kidney Injury* / etiology
Acute Kidney Injury* / veterinary
Animals
Biomarkers
Creatinine / urine
Dog Diseases* / diagnosis
Dog Diseases* / etiology
Dogs
Early Diagnosis
Hemorrhage / veterinary
Hypotension* / diagnosis
Hypotension* / etiology
Hypotension* / veterinary
Lipocalin-2 / urine
Male
Prospective Studies

Substances

Biomarkers
Lipocalin-2
Creatinine