TY - JOUR
T1 - Urinary Biomarkers of Renal Disease in Dogs with X-Linked Hereditary Nephropathy
AU - Nabity, M. B.
AU - Lees, G. E.
AU - Cianciolo, R.
AU - Boggess, M. M.
AU - Steiner, J. M.
AU - Suchodolski, J. S.
PY - 2012/3
Y1 - 2012/3
N2 - 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 < .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.
AB - 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 < .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.
KW - N-acetyl-β-d-glucosaminidase
KW - Neutrophil gelatinase-associated lipocalin
KW - Retinol binding protein
KW - β2-microglobulin
UR - http://www.scopus.com/inward/record.url?scp=84858748755&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858748755&partnerID=8YFLogxK
U2 - 10.1111/j.1939-1676.2012.00891.x
DO - 10.1111/j.1939-1676.2012.00891.x
M3 - Article
C2 - 22356524
AN - SCOPUS:84858748755
SN - 0891-6640
VL - 26
SP - 282
EP - 293
JO - Journal of Veterinary Internal Medicine
JF - Journal of Veterinary Internal Medicine
IS - 2
ER -