Evaluation of Neutrophil Gelatinase‐Associated Lipocalin as a Marker of Kidney Injury in Dogs

Abstract

Background: Acute kidney injury (AKI) is a common and often fatal disorder in dogs. Hypothesis: Urine neutrophil gelatinase-associated lipocalin (NGAL)/creatinine ratio is a sensitive and specific biomarker of AKI in dogs.Animals: Ninety-four dogs. Methods: Prospective study. Dogs were classified as follows: (1) healthy dogs, (2) dogs with lower urinary tract disorders, (3) dogs with chronic kidney disease (CKD), (4) dogs with azotemic International Renal Interest Society (IRIS) AKI Grades II-V, and (5) dogs with IRIS AKI Grade I (nonazotemic). Urinary NGAL was quantitated in each dog using an ELISA assay and concentrations were expressed as a ratio to urinary creatinine concentration from the same specimen, and designated the urinary NGAL/creatinine ratio (UNCR).Results: There was a significant difference in UNCR among the study groups (P < .001). Both the azotemic and nonazotemic AKI groups had higher UNCR when compared with all other groups (P < .001 for all pairs). There was a statistically significant difference in UNCR between dogs diagnosed with CKD compared with dogs with lower urinary tract diseases (P = .005) as well as between dogs with CKD and healthy dogs (P = .001). Receiver operator characteristics (ROC) analysis of UNCR as an indicator of azotemic and nonazotemic AKI had an area under the ROC curve of 0.94 and 0.96, respectively.Conclusions and Clinical Relevance: NGAL/creatinine ratio is a sensitive and specific marker of AKI. It can be used to screen patients at risk for AKI and can be utilized to diagnose milder forms of AKI potentially earlier in the course of the disease.

Neutrophil Gelatinase–Associated Lipocalin in Dogs with Naturally Occurring Renal Diseases

“…Studies have demonstrated that NGAL is a useful biomarker in humans with renal disease,3 but the use of NGAL as a marker in dogs with naturally occurring kidney disease has only recently been explored in AKI 28. The results of this study indicated that NGAL is a promising renal biomarker when serum and urine NGAL concentrations in azotemic dogs, especially those with CKD, are evaluated.…”

“…In dogs with naturally occurring kidney disease, the uNGAL‐to‐creatinine ratio has been used to diagnose AKI 28. However, the prognostic role of NGAL in dogs has not been evaluated yet.…”

Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease

“…Urine immunoglobulin G (uIgG) and urine retinol binding protein (uRBP) were increased in dogs with primary CKD7 and those with renal dysfunction secondary to various systemic diseases including pyometra, babesiosis, and snake envenomation 7, 8, 9, 10, 11, 12, 13, 14, 15. Urine, plasma, and serum neutrophil gelatinase‐associated lipocalin (NGAL) and urine N‐acetyl‐β‐D‐glucosaminidase (uNAG), a renal tubular enzyme, are tubular markers increased in both acute and CKD in dogs 7, 11, 12, 15, 16, 17, 18, 19, 20, 21, 22. Neutrophil gelatinase‐associated lipocalin originates not only in the renal tubules but also from neutrophil granules and many other organs 23.…”

Urinary biomarkers of renal function in dogs and cats: a review

“…Leishmaniasis (Palacio et al 1997) X-linked hereditary nephropathy (Nabity et al 2012) Heartworm disease with cardiac impairment (Uechi et al 1994b) Pyometra Experimental immune complex glomerulonephritis (Bishop et al 1991) Acute renal failure experimentally induced in cats (NAG-B isoenzyme) (Sato et al 2002a) CKD in cats (Jepson et al 2010a) Hypercortisolism Gamma-glutamyl transpeptidase Aminoglycoside-induced nephrotoxicity (Greco et al 1985;Grauer et al 1995;Rivers et al 1996) Renal insufficiency associated with pyometra (De Schepper et al 1989) Heartworm disease with cardiac insufficiency (Uechi et al 1994b) Leishmaniasis (Palacio et al 1997) Envenomation by the common European adder (Palviainen et al 2013) Experimental immune complex glomerulonephritis in cats (Bishop et al 1991) Neutrophil gelatinaseassociated lipocalin Acute kidney injury (Hsu et al 2014a;Segev et al 2013;Zhou et al 2014) Chronic kidney disease (Hsu et al 2014a;Steinbach et al 2014) Retinol binding protein…”