Urinary Neutrophil Gelatinase-associated Lipocalin as a Marker for Identification of Acute Kidney Injury and Recovery in Dogs with Gentamicin-induced Nephrotoxicity

Carrie Palm, G. Segev, Larry D Cowgill, B. E. Leroy, K. L. Kowalkowski, K. Kanakubo, Joellen L Westropp

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: Acute kidney injury (AKI) is associated with high mortality rates in dogs, which may be a consequence of late recognition using traditional diagnostic tests. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein-induced during kidney injury that may identify AKI earlier than traditional tests. Objectives/Hypothesis: To evaluate urinary NGAL (uNGAL) and uNGAL-to-urinary creatinine ratio (UNCR) as early markers of kidney injury and recovery in an AKI model in dogs. It was hypothesized that these markers would document AKI earlier than serum creatinine concentration. Animals: Five purpose-bred dogs. Methods: Prospective study. Acute kidney injury, defined as a > 50% increase in serum creatinine concentration above baseline, was induced in dogs by gentamicin administration (8-10 mg/kg SC q8h). Blood and urine collected for biochemical analyses and uNGAL and urinary creatinine concentrations, respectively, during AKI induction and recovery. Results: Acute kidney injury was diagnosed significantly earlier based on a 7-fold increase in UNCR compared to a > 50% increase in serum creatinine concentration (day 8; range, 2-10 mg/dl vs day 16; range, 14-19 mg/dl; P =.009). During recovery, the initial decrease in UNCR preceded the decrease in serum creatinine concentration by a median of 2 days. The uNGAL changes paralleled UNCR changes, but the increase in uNGAL was triphasic; the initial peak occurred earlier than UNCR (median, day 11 versus median, day 19). Conclusions and Clinical Importance: The UNCR was early marker of gentamicin-induced AKI and its decrease documented onset of renal recovery. Additional studies are needed to validate this marker in dogs with naturally occurring renal injury.

Original languageEnglish (US)
Pages (from-to)200-205
Number of pages6
JournalJournal of Veterinary Internal Medicine
Volume30
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

nephrotoxicity
gentamicin
Gentamicins
Acute Kidney Injury
neutrophils
creatinine
Creatinine
kidneys
Dogs
dogs
blood serum
Kidney
Serum
Wounds and Injuries
Lipocalin-2
Routine Diagnostic Tests
dog breeds
prospective studies
diagnostic techniques
urine

Keywords

  • Acute kidney injury
  • Biomarker
  • Neutrophil gelatinase-associated lipocalin
  • UNGAL to urinary creatinine ratio

ASJC Scopus subject areas

  • veterinary(all)

Cite this

@article{9f6a1a7f0aaf4aa288d8f327d2101408,
title = "Urinary Neutrophil Gelatinase-associated Lipocalin as a Marker for Identification of Acute Kidney Injury and Recovery in Dogs with Gentamicin-induced Nephrotoxicity",
abstract = "Background: Acute kidney injury (AKI) is associated with high mortality rates in dogs, which may be a consequence of late recognition using traditional diagnostic tests. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein-induced during kidney injury that may identify AKI earlier than traditional tests. Objectives/Hypothesis: To evaluate urinary NGAL (uNGAL) and uNGAL-to-urinary creatinine ratio (UNCR) as early markers of kidney injury and recovery in an AKI model in dogs. It was hypothesized that these markers would document AKI earlier than serum creatinine concentration. Animals: Five purpose-bred dogs. Methods: Prospective study. Acute kidney injury, defined as a > 50{\%} increase in serum creatinine concentration above baseline, was induced in dogs by gentamicin administration (8-10 mg/kg SC q8h). Blood and urine collected for biochemical analyses and uNGAL and urinary creatinine concentrations, respectively, during AKI induction and recovery. Results: Acute kidney injury was diagnosed significantly earlier based on a 7-fold increase in UNCR compared to a > 50{\%} increase in serum creatinine concentration (day 8; range, 2-10 mg/dl vs day 16; range, 14-19 mg/dl; P =.009). During recovery, the initial decrease in UNCR preceded the decrease in serum creatinine concentration by a median of 2 days. The uNGAL changes paralleled UNCR changes, but the increase in uNGAL was triphasic; the initial peak occurred earlier than UNCR (median, day 11 versus median, day 19). Conclusions and Clinical Importance: The UNCR was early marker of gentamicin-induced AKI and its decrease documented onset of renal recovery. Additional studies are needed to validate this marker in dogs with naturally occurring renal injury.",
keywords = "Acute kidney injury, Biomarker, Neutrophil gelatinase-associated lipocalin, UNGAL to urinary creatinine ratio",
author = "Carrie Palm and G. Segev and Cowgill, {Larry D} and Leroy, {B. E.} and Kowalkowski, {K. L.} and K. Kanakubo and Westropp, {Joellen L}",
year = "2016",
month = "1",
day = "1",
doi = "10.1111/jvim.13819",
language = "English (US)",
volume = "30",
pages = "200--205",
journal = "Journal of Veterinary Internal Medicine",
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T1 - Urinary Neutrophil Gelatinase-associated Lipocalin as a Marker for Identification of Acute Kidney Injury and Recovery in Dogs with Gentamicin-induced Nephrotoxicity

AU - Palm, Carrie

AU - Segev, G.

AU - Cowgill, Larry D

AU - Leroy, B. E.

AU - Kowalkowski, K. L.

AU - Kanakubo, K.

AU - Westropp, Joellen L

PY - 2016/1/1

Y1 - 2016/1/1

N2 - Background: Acute kidney injury (AKI) is associated with high mortality rates in dogs, which may be a consequence of late recognition using traditional diagnostic tests. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein-induced during kidney injury that may identify AKI earlier than traditional tests. Objectives/Hypothesis: To evaluate urinary NGAL (uNGAL) and uNGAL-to-urinary creatinine ratio (UNCR) as early markers of kidney injury and recovery in an AKI model in dogs. It was hypothesized that these markers would document AKI earlier than serum creatinine concentration. Animals: Five purpose-bred dogs. Methods: Prospective study. Acute kidney injury, defined as a > 50% increase in serum creatinine concentration above baseline, was induced in dogs by gentamicin administration (8-10 mg/kg SC q8h). Blood and urine collected for biochemical analyses and uNGAL and urinary creatinine concentrations, respectively, during AKI induction and recovery. Results: Acute kidney injury was diagnosed significantly earlier based on a 7-fold increase in UNCR compared to a > 50% increase in serum creatinine concentration (day 8; range, 2-10 mg/dl vs day 16; range, 14-19 mg/dl; P =.009). During recovery, the initial decrease in UNCR preceded the decrease in serum creatinine concentration by a median of 2 days. The uNGAL changes paralleled UNCR changes, but the increase in uNGAL was triphasic; the initial peak occurred earlier than UNCR (median, day 11 versus median, day 19). Conclusions and Clinical Importance: The UNCR was early marker of gentamicin-induced AKI and its decrease documented onset of renal recovery. Additional studies are needed to validate this marker in dogs with naturally occurring renal injury.

AB - Background: Acute kidney injury (AKI) is associated with high mortality rates in dogs, which may be a consequence of late recognition using traditional diagnostic tests. Neutrophil gelatinase-associated lipocalin (NGAL) is a protein-induced during kidney injury that may identify AKI earlier than traditional tests. Objectives/Hypothesis: To evaluate urinary NGAL (uNGAL) and uNGAL-to-urinary creatinine ratio (UNCR) as early markers of kidney injury and recovery in an AKI model in dogs. It was hypothesized that these markers would document AKI earlier than serum creatinine concentration. Animals: Five purpose-bred dogs. Methods: Prospective study. Acute kidney injury, defined as a > 50% increase in serum creatinine concentration above baseline, was induced in dogs by gentamicin administration (8-10 mg/kg SC q8h). Blood and urine collected for biochemical analyses and uNGAL and urinary creatinine concentrations, respectively, during AKI induction and recovery. Results: Acute kidney injury was diagnosed significantly earlier based on a 7-fold increase in UNCR compared to a > 50% increase in serum creatinine concentration (day 8; range, 2-10 mg/dl vs day 16; range, 14-19 mg/dl; P =.009). During recovery, the initial decrease in UNCR preceded the decrease in serum creatinine concentration by a median of 2 days. The uNGAL changes paralleled UNCR changes, but the increase in uNGAL was triphasic; the initial peak occurred earlier than UNCR (median, day 11 versus median, day 19). Conclusions and Clinical Importance: The UNCR was early marker of gentamicin-induced AKI and its decrease documented onset of renal recovery. Additional studies are needed to validate this marker in dogs with naturally occurring renal injury.

KW - Acute kidney injury

KW - Biomarker

KW - Neutrophil gelatinase-associated lipocalin

KW - UNGAL to urinary creatinine ratio

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