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.