title: Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease.
abstract: BACKGROUND
  Urine protein loss is common in dogs with chronic kidney disease (CKD).
  
  
  OBJECTIVE
  To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, College Station, TX.
authors.forename: J A
authors.initials: JA
authors.lastname: Hokamp
authors.affiliation: Department of Veterinary Biosciences, The Ohio State University, Columbus, OH.
authors.forename: R E
authors.initials: RE
authors.lastname: Cianciolo
authors.affiliation: School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ.
authors.forename: M
authors.initials: M
authors.lastname: Boggess
authors.affiliation: Department of Small Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, College Station, TX.
authors.forename: G E
authors.initials: GE
authors.lastname: Lees
authors.affiliation: Dipartimento di Sanità Pubblica, Patologia Comparata e Igiene Veterinaria, Facoltà di Medicina Veterinaria, Viale dell'Università, Padua, Italy.
authors.forename: S L
authors.initials: SL
authors.lastname: Benali
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, College Station, TX.
authors.forename: M
authors.initials: M
authors.lastname: Kovarsky
authors.affiliation: Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine and Biomedical Sciences, College Station, TX.
authors.forename: M B
authors.initials: MB
authors.lastname: Nabity
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000652:urine; D004283:Dog Diseases / Q000097:blood / Q000473:pathology* / Q000652:urine; D004285:Dogs; D005260:Female; D008297:Male; D011507:Proteinuria / Q000097:blood / Q000652:urine / Q000662:veterinary*; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000652:urine / Q000662:veterinary*; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers
keywords: Immunoglobulin G; Immunoglobulin M; N-acetyl-β-D-glucosaminidase; Neutrophil gelatinase-associated lipocalin; Retinol binding protein
references.citation: Vet Clin Pathol. 2011 Jun;40(2):222-36
references.pmid: 21446987
references.citation: J Vet Intern Med. 2013 Nov-Dec;27 Suppl 1:S67-75
references.pmid: 24635383
references.citation: J Vet Intern Med. 2013 Sep-Oct;27(5):998-1010
references.pmid: 23952327
references.citation: J Vet Intern Med. 2010 Nov-Dec;24(6):1263-70
references.pmid: 21039862
references.citation: Histochem J. 1999 Jul;31(7):433-41
references.pmid: 10475571
references.citation: Am J Vet Res. 2010 Nov;71(11):1387-94
references.pmid: 21034333
references.citation: Adv Chronic Kidney Dis. 2005 Oct;12(4):353-65
references.pmid: 16198274
references.citation: Kidney Int. 2003 Mar;63(3):809-25
references.pmid: 12631062
references.citation: BMC Med. 2009 Aug 04;7:39
references.pmid: 19653885
references.citation: Am J Vet Res. 2009 Feb;70(2):297-301
references.pmid: 19231965
references.citation: Diabetes Res Clin Pract. 2012 Jan;95(1):139-44
references.pmid: 22078636
references.citation: J Vet Intern Med. 2014 Mar-Apr;28(2):437-42
references.pmid: 24417186
references.citation: Vet Clin Pathol. 2008 Mar;37(1):4-20
references.pmid: 18366540
references.citation: J Toxicol Sci. 2013;38(2):269-77
references.pmid: 23535405
references.citation: J Am Vet Med Assoc. 2005 Feb 1;226(3):393-400
references.pmid: 15702689
references.citation: J Vet Diagn Invest. 2004 Jul;16(4):271-7
references.pmid: 15305736
references.citation: J Vet Med Sci. 2002 Apr;64(4):361-5
references.pmid: 12014583
references.citation: J Vet Intern Med. 2010 Jan-Feb;24(1):65-72
references.pmid: 20041990
references.citation: Vet Clin North Am Small Anim Pract. 2004 Jul;34(4):867-85, v
references.pmid: 15223206
references.citation: J Vet Intern Med. 2012 Mar-Apr;26(2):282-93
references.pmid: 22356524
references.citation: Vet Pathol. 2016 Jan;53(1):113-35
references.pmid: 25957358
references.citation: J Vet Intern Med. 2005 May-Jun;19(3):377-85
references.pmid: 15954557
references.citation: J Vet Intern Med. 2014 Mar-Apr;28(2):264-9
references.pmid: 24417647
references.citation: J Vet Intern Med. 2011 Sep-Oct;25(5):1075-83
references.pmid: 21848947
references.citation: J Vet Intern Med. 2013 Nov-Dec;27(6):1362-7
references.pmid: 24020513
references.citation: Vet J. 2013 Oct;198(1):239-44
references.pmid: 23916665
references.citation: Toxicol Appl Pharmacol. 2014 Oct 1;280(1):30-5
references.pmid: 25034533
references.citation: Vet Rec. 2013 Nov 9;173(18):452
references.pmid: 24106249
references.citation: Vet J. 2014 Dec;202(3):588-96
references.pmid: 25458884
references.citation: Toxicol Pathol. 1986;14(1):101-8
references.pmid: 3715325
references.citation: Vet Parasitol. 2012 Dec 21;190(3-4):326-32
references.pmid: 22884913
references.citation: Res Vet Sci. 2013 Dec;95(3):1181-5
references.pmid: 24074691