Urinary Markers in Healthy Young and Aged Dogs and Dogs with Chronic Kidney Disease

Abstract

Background: Blood urea nitrogen and serum creatinine concentrations only detect a decrease of 475% of renal functional mass. Therefore, there is a need for markers that allow early detection and localization of renal damage.Hypothesis: Urinary albumin (uALB), C-reactive protein (uCRP), retinol binding protein (uRBP), and N-acetyl-b-Dglucosaminidase (uNAG) concentrations are increased in dogs with chronic kidney disease (CKD) compared with healthy controls and in healthy older dogs compared with young dogs.Animals: Ten dogs with CKD, 10 healthy young dogs (age 1-3 years), and 10 healthy older dogs (age 4 7 years) without clinically relevant abnormalities on physical examination, hematology, biochemistry, and urinalysis.Methods: Urinary markers were determined using an ELISA (uALB, uCRP, and uRBP) or a colorimetric test (uNAG). Results were related to urinary creatinine (c). The fixed effects model or the Wilcoxon rank sum test were used to compare the different groups of dogs.Results: uALB/c, uRBP/c, and uNAG/c were significantly higher in CKD dogs than in healthy dogs. No significant difference was found for uCRP, which was not detectable in the healthy dogs and only in 3 of the CKD dogs. Between the healthy young and older dogs, no significant difference was detected for any of the markers.Conclusion: The urinary markers uALB/c, uRBP/c, and uNAG/c were significantly increased in dogs with CKD compared with healthy controls. Additional studies are needed to evaluate the ability of these markers to detect renal disease before the onset of azotemia.

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

“…N‐acetyl‐β‐D‐glucosaminidase, which is approximately the size of IgG, does not pass through a normal glomerular filtration barrier, and the upper reference limit for uNAG/c in healthy dogs (3.63 U/g)27 is well below the mean in this study. Previous studies have shown increased uNAG/c in dogs with CKD, presumed to be because of tubular damage or increased lysosomal turnover secondary to proteinuria 7, 15, 19. While it is still possible that NAG leakage is occurring without histologic evidence of tubular damage, the strong correlation with glomerular damage and lack of correlation with TI damage in this study supports the possibility that NAG can pass through an injured glomerular filtration barrier.…”

“…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.…”

Assessment of renal dysfunction using urinary markers in canine babesiosis caused by Babesia rossi

“…Retinol binding protein (RBP) is filtered through the renal glomeruli because of its low molecular weight and is reabsorbed in the proximal tubules under physiological circumstances (Christensen et al, 1999). Therefore, increased urinary RBP (uRBP) indicates tubular dysfunction, as previously reported in dogs with E. coli pyo met ra, C KD , and Cushing's syndrome Smets et al, 2010b;Smets et al, 2011).…”

“…The latter study failed to find an association between serum CRP concentration and outcome in canine babesiosis (Köster et al, 2009). Urinary CRP was previously measured in dogs with E. coli pyometra, Leptospirosis, and CKD Oliveira et al, 2010;Smets et al, 2010b). The glomerular barrier must be (Raila et al, 2003a;Raila et al, 2003b).…”

“…Glomerular damage consequently leads to the urinary presence of these HMW proteins. Urinary IgG (uIgG) and/or urinary CRP (uCRP) detected glomerular dysfunction in dogs with Escherichia coli pyometra, chronic kidney disease (CKD), and Cushing's syndrome Smets et al, 2010b;Smets et al, 2011). Retinol binding protein (RBP) is filtered through the renal glomeruli because of its low molecular weight and is reabsorbed in the proximal tubules under physiological circumstances (Christensen et al, 1999).…”