Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease

Background: Urine protein loss is common in dogs with chronic kidney disease (CKD). Hypothesis/Objectives: To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD. Animals: One hunderd and eighty dogs with naturally occurring kidney disease. Methods: Retrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined. Results: Fractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P < .01). Serum creatinine (SCr) correlated most strongly with TI damage (r = 0.70, P < .01). Urine IgM/creatinine and urine NAG/creatinine had the highest sensitivity (75%) and specificity (78%) for detection of immune complex-mediated glomerulonephritis. Although individually most biomarkers were significantly associated with decreased survival time (P < .05), in a multivariate analysis, SCr, IgM_FE, and glomerular damage based on transmission electron microscopy (TEM) were the only biomarkers significantly associated with survival time (SCr: P = .001; IgM_FE: P = .008; TEM: P = .017). Conclusions and Clinical Importance: Novel urine biomarkers and FEs are useful for detection of glomerular and TI damage in dogs with proteinuric CKD and might predict specific disease types and survival.