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. 2016 Mar-Apr;30(2):591-601.
doi: 10.1111/jvim.13832. Epub 2016 Feb 1.

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

J A Hokamp  1 , R E Cianciolo  2 , M Boggess  3 , G E Lees  4 , S L Benali  5 , M Kovarsky  1 , M B Nabity  1
Affiliations

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

J A Hokamp et al. J Vet Intern Med. 2016 Mar-Apr.

Abstract

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.

Keywords: Immunoglobulin G; Immunoglobulin M; N-acetyl-β-D-glucosaminidase; Neutrophil gelatinase-associated lipocalin; Retinol binding protein.

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Figures

Figure 1
Figure 1
Correlations of biomarkers with glomerular damage based on light microscopy, with 95% confidence intervals. Circles represent a statistically significant correlation and triangles represent no significant correlation. **P < .01; n = 176. SCr, serum creatinine; USG, urine specific gravity; UPC, urine protein:creatinine ratio; uIgG/c, urine immunoglobulin G/urine creatinine; IgG_FE, fractional excretion of immunoglobulin G; uIgM/c, urine immunoglobulin M/urine creatinine; IgM_FE, fractional excretion of immunoglobulin M; uRBP/c, urine retinol binding protein/urine creatinine; sRBP, serum retinol binding protein; RBP_FE, fractional excretion of retinol binding protein; uNGAL/c, urine neutrophil gelatinase‐associated lipocalin/urine creatinine; sNGAL, serum neutrophil gelatinase‐associated lipocalin; NGAL_FE, fractional excretion of neutrophil gelatinase‐associated lipocalin; uNAG/c, urine N‐acetyl‐β‐D‐glucosaminidase/urine creatinine.
Figure 2
Figure 2
Correlations of biomarkers with glomerular damage based on transmission electron microscopy with 95% confidence intervals. Circles represent a statistically significant correlation and triangles represent no significant correlation. **P < .01; n = 151. SCr, serum creatinine; USG, urine specific gravity; UPC, urine protein:creatinine ratio; uIgG/c, urine immunoglobulin G/urine creatinine; IgG_FE, fractional excretion of immunoglobulin G; uIgM/c, urine immunoglobulin M/urine creatinine; IgM_FE, fractional excretion of immunoglobulin M; uRBP/c, urine retinol binding protein/urine creatinine; sRBP, serum retinol binding protein; RBP_FE, fractional excretion of retinol binding protein; uNGAL/c, urine neutrophil gelatinase‐associated lipocalin/urine creatinine; sNGAL, serum neutrophil gelatinase‐associated lipocalin; NGAL_FE, fractional excretion of neutrophil gelatinase‐associated lipocalin; uNAG/c, urine N‐acetyl‐β‐D‐glucosaminidase/urine creatinine.
Figure 3
Figure 3
Correlations of biomarkers with tubulointerstitial damage based on light microscopy with 95% confidence intervals. Circles represent a statistically significant correlation and triangles represent no significant correlation. *P < .05; **P < .01; n = 176. SCr, serum creatinine; USG, urine specific gravity; UPC, urine protein:creatinine ratio; uIgG/c, urine immunoglobulin G/urine creatinine; IgG_FE, fractional excretion of immunoglobulin G; uIgM/c, urine immunoglobulin M/urine creatinine; IgM_FE, fractional excretion of immunoglobulin M; uRBP/c, urine retinol binding protein/urine creatinine; sRBP, serum retinol binding protein; RBP_FE, fractional excretion of retinol binding protein; uNGAL/c, urine neutrophil gelatinase‐associated lipocalin/urine creatinine; sNGAL, serum neutrophil gelatinase‐associated lipocalin; NGAL_FE, fractional excretion of neutrophil gelatinase‐associated lipocalin; uNAG/c, urine N‐acetyl‐β‐D‐glucosaminidase/urine creatinine.
Figure 4
Figure 4
Probability of survival by biomarker/damage score for a dog at median age (7 years) at different starting values of biomarkers/damage scores for (A) SCr (n = 83); (B) IgM_FE (n = 67); (C) TEM Glomerular Damage Score (n = 73). 25p: 25th percentile; 50p: 50th percentile; 75p: 75th percentile; 90p: 90th percentile; 95p: 95th percentile. SCr, serum creatinine; IgM_FE, fractional excretion of immunoglobulin M; TEM, transmission electron microscopy.
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