title: Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs.
abstract: BACKGROUND
  Symmetric dimethylarginine (SDMA) is a small molecule formed by methylation of arginine, and released into blood during protein degradation. SDMA is primarily eliminated by renal excretion and is a promising endogenous marker of glomerular filtration rate (GFR).
  
  
  OBJECTIVE
  To validate an assay for SDMA measurement, determine stability of SDMA in blood, and compare SDMA with serum creatinine concentration (sCr) and GFR for early detection of decreasing kidney function in dogs with chronic kidney disease (CKD).
  
  
  METHODS
  Eight male dogs affected with X-linked hereditary nephropathy and 4 unaffected male littermates.
  
  
  METHODS
  Prospective study validating SDMA measurement using liquid chromatography-mass spectrometry, assessing stability of SDMA in serum and plasma, and serially determining sCr, SDMA, and GFR (using iohexol clearance) in dogs during progression from preclinical disease to end-stage renal failure. Correlations were determined using linear regression. Timepoints at which sCr, SDMA, and GFR identified decreased renal function were compared using defined cutoffs, trending in an individual dog, and comparison with unaffected littermates.
  
  
  RESULTS
  Symmetric dimethylarginine was highly stable in serum and plasma, and the assay demonstrated excellent analytical performance. In unaffected dogs, SDMA remained unchanged whereas in affected dogs, SDMA increased during disease progression, correlating strongly with an increase in sCr (r = 0.95) and decrease in GFR (r = -0.95). Although trending improved sCr's sensitivity, SDMA identified, on average, <20% decrease in GFR, which was earlier than sCr using any comparison method.
  
  
  CONCLUSIONS
  Symmetric dimethylarginine is useful for both early identification and monitoring of decreased renal function in dogs with CKD.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
authors.forename: M B
authors.initials: MB
authors.lastname: Nabity
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX.
authors.forename: G E
authors.initials: GE
authors.lastname: Lees
authors.affiliation: School of Mathematical and Statistical Sciences, Arizona State University, Tempe, AZ.
authors.forename: M M
authors.initials: MM
authors.lastname: Boggess
authors.affiliation: IDEXX Laboratories Inc., Westbrook, ME.
authors.forename: M
authors.initials: M
authors.lastname: Yerramilli
authors.affiliation: IDEXX Laboratories Inc., Westbrook, ME.
authors.forename: E
authors.initials: E
authors.lastname: Obare
authors.affiliation: IDEXX Laboratories Inc., Westbrook, ME.
authors.forename: M
authors.initials: M
authors.lastname: Yerramilli
authors.affiliation: IDEXX Laboratories Inc., Westbrook, ME.
authors.forename: A
authors.initials: A
authors.lastname: Rakitin
authors.affiliation: IDEXX Laboratories Inc., Westbrook, ME.
authors.forename: J
authors.initials: J
authors.lastname: Aguiar
authors.affiliation: IDEXX Laboratories Inc., Westbrook, ME.
authors.forename: R
authors.initials: R
authors.lastname: Relford
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004283:Dog Diseases; D004285:Dogs / Q000097:blood; D042241:Early Diagnosis; D005919:Glomerular Filtration Rate / Q000662:veterinary; D008297:Male; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000175:diagnosis / Q000662:veterinary*; D015203:Reproducibility of Results
chemical_list: D015415:Biomarkers; C024917:symmetric dimethylarginine; D001120:Arginine
keywords: X-linked hereditary nephropathy; canine; glomerular filtration rate; serum creatinine