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Characterization and Comparison of Urine and Serum Proteins with Renal Biopsy Findings and Clinical Data in Dogs with Naturally Occurring Proteinuric Renal Diseases
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Chronic kidney disease (CKD) results in significant morbidity and mortality in dogs, and urine protein loss is common in dogs with CKD. Currently available noninvasive biomarkers for evaluating CKD in dogs cannot accurately predict the severity of glomerular and tubulointerstitial (TI) damage or the cause of CKD without renal biopsy. Non-invasive indicators of degree of renal damage, disease type, and prognosis would be ideal for clinicians and owners. Study goals were to evaluate novel protein biomarkers and electrophoretic banding patterns as indicators of glomerular and TI damage, specific disease type, and survival in dogs with naturally occurring proteinuric CKD. These retrospective studies used urine, serum, and renal biopsies from 200+ dogs with CKD. Selected urinary protein biomarkers (immunoglobulins G and M, retinol binding protein, neutrophil gelatinase associated lipocalin, and N-acetyl-β D-glucosaminidase (NAG)) and electrophoretic urinary protein banding patterns were evaluated and correlated with histologic damage on renal biopsies, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined. The odds of altered urinary biomarkers and banding patterns being associated with increased risk of death due to renal disease were also determined. Fractional excretions of immunoglobulin M (IgM) and immunoglobulin G correlated most strongly with glomerular damage based on light microscopy, while serum creatinine correlated most strongly with TI damage. Urinary IgM and NAG were significantly associated with immune complex-mediated glomerulonephritis (ICGN), and urinary IgM in particular had high specificity for ICGN above 13.6 ng/ml or 14.4 μg/mg. Electrophoretic protein banding patterns had excellent sensitivity and specificity for detection of glomerular damage and good sensitivity and excellent specificity for detection of TI damage, and banding patterns were moderately correlated with histologic severity of glomerular and TI damage. Increases in most protein biomarkers, degree of severity of electrophoretic protein banding patterns, and degree of histologic glomerular and TI damage were significantly associated with an increased risk of death due to renal disease. Novel urine biomarkers and electrophoretic protein banding patterns are useful for detection of glomerular and TI damage, prediction of specific disease types (in particular, ICGN), and prediction of risk of death in dogs with proteinuric CKD.
chronic kidney disease
immune complex-mediated glomerulonephritis
sodium dodecyl sulfate polyacrylamide gel electrophoresis
neutrophil gelatinase-associated lipocalin
retinol binding protein
Hokamp, Jessica Anne (2016). Characterization and Comparison of Urine and Serum Proteins with Renal Biopsy Findings and Clinical Data in Dogs with Naturally Occurring Proteinuric Renal Diseases. Doctoral dissertation, Texas A & M University. Available electronically from