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

Abstract

BackgroundUrine protein loss is common in dogs with chronic kidney disease (CKD).Hypothesis/ObjectivesTo evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD.AnimalsOne hunderd and eighty dogs with naturally occurring kidney disease.MethodsRetrospective 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.ResultsFractional 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 ImportanceNovel 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.

Correlation of electrophoretic urine protein banding patterns with severity of renal damage in dogs with proteinuric chronic kidney disease

“…Samples were shipped chilled and typically received and processed within 24 hours post collection. Urine specific gravity (USG, Rhino VET360 Veterinary Clinical Refractometer; Reichert Technologies, Depew, NY), UPC (Creatinine LiquiColor Test [Endpoint], Protein, Micro LiquiColor Test [CSF and Urine], and Sirrus Clinical Chemistry Analyzer; Stanbio Laboratory, Boerne, TX), and serum creatinine (sCr, Creatinine LiquiColor Test [Endpoint] and Sirrus Clinical Chemistry Analyzer; Stanbio Laboratory) were determined in our laboratory as previously described . Urine supernatant from each dog was aliquoted and stored at −80°C.…”

“…Bacteriuria was present if bacteria were seen on sediment examination or if culture results were positive. Kidney biopsies were processed for light microscopy (LM) and transmission electron microscopy (TEM) as previously described . Renal disease was diagnosed if dogs had persistent proteinuria, azotemia, or both.…”

“…Urinalysis was performed within 2 hours of collection for all samples. UPC and sCr were determined for each sample as previously described . Urine supernatant and serum were stored at −80°C before analysis.…”

“…Kidney biopsies were evaluated for glomerular damage (by LM and/or TEM) and TI damage (by LM) and scored as previously described (biopsy scoring algorithm in Tables , , ). The LM glomerular damage score used a 0‐3 ordinal scale: 0 = normal glomeruli; 1 = mild or focal lesions; 2 = moderate lesions; and 3 = severe lesions.…”

“…Renal proteinuria, or the abnormal presence of proteins in urine due to renal disease, is common in canine CKD . Major mechanisms of renal proteinuria include abnormal transglomerular passage of proteins due to increased permeability of the glomerular filtration barrier, impaired reabsorption of proteins by proximal tubular epithelial cells, and release of proteins/enzymes from damaged tubular epithelial cells . In addition to being a hallmark of glomerular disease in dogs, renal proteinuria is also associated with kidney disease progression .…”