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

Abstract

BackgroundNeutrophil gelatinase–associated lipocalin (NGAL) is released from renal tubular cells after injury and serves in humans as a real‐time indicator of active kidney damage, including acute kidney injury (AKI) and chronic kidney disease (CKD). However, NGAL concentrations in dogs with naturally occurring AKI or CKD rarely have been explored in detail.Hypothesis/ObjectivesThe goal of this study was to evaluate whether NGAL can serve as a useful biomarker in dogs with naturally occurring renal disease.AnimalsClient‐owned dogs with renal disease (57) and control dogs without any disease (12) were examined.MethodsSerum NGAL (sNGAL) and urine NGAL (uNGAL) concentrations were measured in each animal by a newly developed ELISA system. Demographic, hematologic, and serum biochemical data were recorded. Survival attributable to AKI and CKD was evaluated at 30 days and 90 days, respectively.ResultsSerum and urine NGAL concentrations in azotemic dogs were significantly higher than in nonazotemic dogs and were highly correlated with serum creatinine concentration (P < .05). Among CKD dogs, death was associated with significantly higher sNGAL and uNGAL concentrations compared with survivors. Receiver‐operating characteristic curve (ROC) analysis showed that sNGAL was better than serum creatinine concentration when predicting clinical outcomes for CKD dogs (P < .05). The best cutoff point for sNGAL was 50.6 ng/mL, which gave a sensitivity and a specificity of 76.9 and 100%, respectively. Furthermore, dogs that had higher concentrations of sNGAL survived for a significantly shorter time.Conclusion sNGAL is a useful prognostic marker when evaluating dogs with CKD.

Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

“…4,24,25,26 Similar efforts are underway in veterinary medicine and show great promise. [28][29][30][31][32][33][34][35][36] (See also, Yerramilli in this issue) An AKI biomarker should be detectable in urine and/or plasma such that it can be assessed routinely and serve as an indicator of kidney function or dysfunction or response to injury. The ideal marker should reflect kidney specific events, be unique and specific to the kidney, and reflect very early and potentially sustained phases of the pathogenesis and repair processes.…”

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…”

“…The significant increase of NGAL in urine was detected as early as 12 h after surgery, much earlier than the increase in serum creatinine. Urinary NGAL was recommended as a sensitive and specific biomarker for the detection of AKI, for prediction of nephrotoxicity, and to screen patients at risk for AKI (Table 1) (Lee et al 2012;Kai et al 2013;Hsu et al 2014a;Zhou et al 2014). NGAL was found to be a more sensitive biomarker for the detection of gentamicin-induced renal proximal tubular toxicity than NAG (Zhou et al 2014).…”

“…Urine NGAL concentrations were highly correlated with serum creatinine concentrations. Among CKD dogs, death was associated with significantly higher uNGAL concentrations compared with survivors (Hsu et al 2014a). Recent studies in rats and children found that urinary NGAL increases significantly in the presence of urinary tract infection (Ichino et al doi: 10.17221/8527-VETMED 2009; Decavele et al 2011).…”