Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs

Abstract

BackgroundSymmetric 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).ObjectivesTo 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).AnimalsEight male dogs affected with X‐linked hereditary nephropathy and 4 unaffected male littermates.MethodsProspective 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.ResultsSymmetric 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 and Clinical ImportanceSymmetric dimethylarginine is useful for both early identification and monitoring of decreased renal function in dogs with CKD.

X-Linked Alport Dogs Demonstrate Mesangial Filopodial Invasion of the Capillary Tuft as an Early Event in Glomerular Damage

“…Physiologic data, including serum creatinine (sCr), urine protein: urine creatinine ratio (UPC), and symmetric dimethylarginine (SDMA) were used as previously described [32] to detect advancement of disease defined by set milestones (MS). SDMA is a methylated arginine that is released in the blood during protein degradation and excreted by the kidneys.…”

“…In dogs, it serves as a useful marker for evaluation of decreasing renal function. [32] Milestones were defined by the following criteria: MS 1-presence of microalbuminuria for two consecutive weeks (average age 14.1 weeks), MS 2-UPC ≥ 2 for two consecutive weeks (average age 20.1 weeks), MS 3-sCr ≥ 1.2 mg/dL (average age 28.8 weeks), MS 4-sCr ≥ 2.4 (average age 35.0 weeks), and MS 5-sCr ≥ 5 mg/dL (average age 39.5 weeks). Testing for microalbuminuria was performed only until MS 1 was reached using a semi-quantitative test (E.R.D.…”

Conceitos E Aplicabilidade Dos Principais Biomarcadores Na Nefrologia Veterinária – Revisão De Literatura

“…Já em soro de cães e gatos a melhor forma de se mensurar SDMA é através da cromatografia líquida acoplada à espectrometria de massa (LC-MS) (HALL et al 2014) Em humanos com aumento da concentração de triglicérides, ácido úrico e colesterol (LDL), o valor de SDMA sofre variação (TENDERENDA-BANASIUK et al (2013). No entanto, esse biomarcador parece não sofrer nenhuma interferência na sua mensuração em soro e plasma de cães e gatos (NABITY et al 2015).…”

“…A SDMA é eliminada principalmente por excreção renal, surgindo como um potencial marcador endógeno de TFG (NABITY et al 2015). Em cães com doença renal crônico (DRC), a SDMA constatou um aumento médio de 4-5 semanas antes da creatinina sérica, juntamente com a diminuição da taxa de filtração glomerular (HONKAMP E NABITY.…”

Diagnostic challenges and surgical treatment of hydroureteronephrosis in a rabbit (Oryctolagus cuniculus)

“…Urine protein to creatinine ratio (UPCR) and γ-glutamyltransferase (γ-GT)
 index are tests commonly used in small animal medicine but have yet to be used for establishment of contralateral kidney function in exotic companion mammals. Although other diagnostic markers such as asymmetric dimethylarginine and indoxyl sulphate are becoming available for cats and dogs, assay validation and reference intervals of these are not currently available for rabbits (Cheng and others 2015, Nabity and others 2015). Intravenous pyelography or contrast administration at CT may also be useful in assessing renal function in rabbits, but are contraindicated in cases of haemodynamic defects or heart failure and may cause contrast medium-induced renal failure or allergic reactions (Harcourt-Brown 2013).…”