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

J. A. Hokamp, R. E. Cianciolo, May Boggess, G. E. Lees, S. L. Benali, M. Kovarsky, M. B. Nabity

Research output: Contribution to journalArticle

10 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)591-601
Number of pages11
JournalJournal of Veterinary Internal Medicine
Volume30
Issue number2
DOIs
StatePublished - Mar 1 2016

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kidney diseases
Chronic Renal Insufficiency
biomarkers
urine
Biomarkers
kidneys
Urine
Dogs
Creatinine
creatinine
Kidney
Immunoglobulin M
dogs
Serum
Kidney Diseases
Transmission Electron Microscopy
Immunoglobulin G
transmission electron microscopy
Sensitivity and Specificity
glomerulonephritis

Keywords

  • Immunoglobulin G
  • Immunoglobulin M
  • N-acetyl-β-D-glucosaminidase
  • Neutrophil gelatinase-associated lipocalin
  • Retinol binding protein

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease. / Hokamp, J. A.; Cianciolo, R. E.; Boggess, May; Lees, G. E.; Benali, S. L.; Kovarsky, M.; Nabity, M. B.

In: Journal of Veterinary Internal Medicine, Vol. 30, No. 2, 01.03.2016, p. 591-601.

Research output: Contribution to journalArticle

Hokamp, J. A. ; Cianciolo, R. E. ; Boggess, May ; Lees, G. E. ; Benali, S. L. ; Kovarsky, M. ; Nabity, M. B. / Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease. In: Journal of Veterinary Internal Medicine. 2016 ; Vol. 30, No. 2. pp. 591-601.
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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.",
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AU - Hokamp, J. A.

AU - Cianciolo, R. E.

AU - Boggess, May

AU - Lees, G. E.

AU - Benali, S. L.

AU - Kovarsky, M.

AU - Nabity, M. B.

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N2 - 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.

AB - 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.

KW - Immunoglobulin G

KW - Immunoglobulin M

KW - N-acetyl-β-D-glucosaminidase

KW - Neutrophil gelatinase-associated lipocalin

KW - Retinol binding protein

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