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Keywords:

  • N-acetyl-β-d-glucosaminidase;
  • Neutrophil gelatinase-associated lipocalin;
  • Retinol binding protein;
  • β2-microglobulin

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.