Urinary Biomarkers of Renal Disease in Dogs with X‐Linked Hereditary Nephropathy

• Published in: Journal of veterinary internal medicine 2012-03, Vol.26 (2), p.282-293
• Main Authors: Nabity, M.B., Lees, G.E., Cianciolo, R., Boggess, M.M., Steiner, J.M., Suchodolski, J.S.
• Format: Article
• Language: English
• Subjects: Acetylglucosaminidase - urine; Animals; beta 2-Microglobulin - urine; Biomarkers - urine; Biopsy - veterinary; Creatinine - urine; Dog Diseases - genetics; Dog Diseases - pathology; Dog Diseases - urine; Dogs; Genetic Diseases, X-Linked - genetics; Genetic Diseases, X-Linked - pathology; Genetic Diseases, X-Linked - urine; Genetic Diseases, X-Linked - veterinary; Glomerular Filtration Rate - veterinary; Histocytochemistry - veterinary; Linear Models; Lipocalins - urine; Male; Nephritis, Hereditary - genetics; Nephritis, Hereditary - pathology; Nephritis, Hereditary - urine; Nephritis, Hereditary - veterinary; Neutrophil gelatinase‐associated lipocalin; N‐acetyl‐β‐d‐glucosaminidase; Retinol binding protein; Retinol-Binding Proteins - urine; Retrospective Studies; β2‐microglobulin
• ISSN: 0891-6640; 1939-1676
• DOI: 10.1111/j.1939-1676.2012.00891.x

Background Sensitive and specific biomarkers for early tubulointerstitial injury are lacking. Hypothesis The excretion of certain urinary proteins will correlate with the state of renal injury in dogs with chronic kidney disease. Animals Twenty‐five male colony dogs affected with X‐linked hereditary nephropathy (XLHN) and 19 unaffected male littermates were evaluated. Methods 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. Results 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