With the exception of histological evaluation, all work was performed at Texas A&M University. Histological evaluation was performed at North Carolina State University.
Urinary Biomarkers of Renal Disease in Dogs with X-Linked Hereditary Nephropathy
Article first published online: 22 FEB 2012
Copyright © 2012 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 26, Issue 2, pages 282–293, March-April 2012
How to Cite
Nabity, M.B., Lees, G.E., Cianciolo, R., Boggess, M.M., Steiner, J.M. and Suchodolski, J.S. (2012), Urinary Biomarkers of Renal Disease in Dogs with X-Linked Hereditary Nephropathy. Journal of Veterinary Internal Medicine, 26: 282–293. doi: 10.1111/j.1939-1676.2012.00891.x
Presented in part at the 2009 ACVIM Forum, Montreal, Canada, June 2009, at the 45th Annual Meeting of the American Society for Veterinary Clinical Pathology, Baltimore, MD, on October 31, 2010, and at the International Society of Nephrology Forefronts Symposium, Aarhus, Denmark, on September 22–25, 2011.
- Issue published online: 20 MAR 2012
- Article first published online: 22 FEB 2012
- Manuscript Accepted: 9 JAN 2012
- Manuscript Revised: 1 NOV 2011
- Manuscript Received: 25 AUG 2011
- Morris Animal Foundation. Grant Number: C07-311
- National Institutes of Health. Grant Numbers: DK57676, DK64273
- Neutrophil gelatinase-associated lipocalin;
- Retinol binding protein;
Sensitive and specific biomarkers for early tubulointerstitial injury are lacking.
The excretion of certain urinary proteins will correlate with the state of renal injury in dogs with chronic kidney disease.
Twenty-five male colony dogs affected with X-linked hereditary nephropathy (XLHN) and 19 unaffected male littermates were evaluated.
Retrospective analysis of urine samples collected every 2–4 weeks was performed. Urine proteins evaluated were retinol binding protein (uRBP/c), β2-microglobulin (uB2M), N-acetyl-β-d-glucosaminidase (uNAG/c), neutrophil gelatinase-associated lipocalin (uNGAL/c), and immunoglobulin G (uIgG/c). Results were correlated with serum creatinine concentration (sCr), glomerular filtration rate (GFR), urine protein : creatinine ratio, and histopathologic analysis of serial renal biopsies. Analytical validation was performed for all assays; uNAG stability was evaluated.
All urinary biomarkers distinguished affected dogs from unaffected dogs early in their disease process, increasing during early and midstages of disease. uRBP/c correlated most strongly with conventional measures of disease severity, including increasing sCr (r = 0.89), decreasing GFR (r = −0.77), and interstitial fibrosis (r = 0.80), P < .001. However, multivariate analysis revealed age, sCr, uIgG/c, and uB2M, but not uRBP/c, as significant independent predictors of GFR (P < .05).
Conclusions and Clinical Importance
All urinary biomarkers were elevated before sCr increased, but typically after proteinuria developed in dogs with progressive glomerular disease because of XLHN. uRBP/c measurement might be promising as a noninvasive tool for diagnosis and monitoring of tubular injury and dysfunction in dogs.