BackgroundSymmetric dimethylarginine (SDMA) has been shown to be an accurate and precise biomarker for calculating estimated glomerular filtration rate (GFR) in humans, as well as a more sensitive biomarker than serum creatinine concentration (sCr) for assessing renal dysfunction.ObjectivesThe purpose of this retrospective study was to report on the utility of measuring serum SDMA concentrations in cats for detection of chronic kidney disease (CKD) before diagnosis by conventional measurement of sCr.AnimalsChronic kidney disease cats (n = 21) included those persistently azotemic for ≥3 months (n = 15), nonazotemic cats with GFR >30% decreased from median GFR of normal cats (n = 4), and nonazotemic cats with calcium oxalate kidney stones (n = 2). Healthy geriatric cats (n = 21) were selected from the same colony.MethodsSymmetric dimethylarginine concentrations (liquid chromatography‐mass spectroscopy) and sCr (enzymatic colorimetry) were determined retrospectively from historical data or banked serum samples in azotemic cats or at the time GFR (iohexol clearance) was measured in nonazotemic cats.ResultsSerum SDMA (r = −0.79) and sCr (r = −0.77) concentrations were significantly correlated to GFR (both P < .0001). Symmetric dimethylarginine became increased before sCr in 17/21 cats (mean, 17.0 months; range, 1.5–48 months). Serum SDMA had higher sensitivity (100%) compared with sCr (17%), but lower specificity (91% versus 100%) and positive predictive value (86% versus 100%).Conclusion and Clinical ImportanceUsing serum SDMA as a biomarker for CKD allows earlier detection of CKD in cats compared with sCr, which may be desirable for initiating renoprotective interventions that slow progression of CKD.
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.
BackgroundSymmetric dimethylarginine (SDMA) is an accurate and precise biomarker for estimating glomerular filtration rate (GFR) in humans and cats. Serum creatinine (sCr) also correlates with GFR, but has limitations as a biomarker of renal function because nonrenal factors can influence its concentration.HypothesisDifferences in lean body mass (LBM) influence sCr, but not serum SDMA concentrations.AnimalsForty‐one healthy Beagles, mean age 9.9 years (range: 3.1–14.8 years), were studied over a 6 month period.MethodsSerum biomarkers of renal function were measured prospectively at baseline, and 1, 3, and 6 months. SDMA concentrations were measured by liquid chromatography‐mass spectroscopy and sCr concentrations by enzymatic colorimetry. Body composition was determined by dual energy x‐ray absorptiometry.Results LBM (P < .001) and age (P = .006) were significant explanatory variables for sCr concentration (R 2 = 0.38), but not SDMA concentration. Time on food was the only significant explanatory variable for SDMA concentration (R 2 = 0.49). SDMA concentrations decreased across time (P < .001). LBM was affected by sex (males > females; P = .02). Mature adult dogs (<8 years) had greater LBM compared with geriatric dogs (≥8 years; P < .001).Conclusion and Clinical Importance sCr concentrations, but not SDMA concentrations, are influenced by LBM, which limits sCr utility as a biomarker for monitoring renal function in dogs with decreased LBM. Reductions in LBM can lower sCr concentration and overestimate GFR. SDMA concentrations, but not sCr concentrations were influenced by time on food. SDMA could have clinical advantages over sCr in monitoring response to nutritional interventions.
BackgroundSerum concentrations of symmetric dimethylarginine (SDMA) detected chronic kidney disease (CKD) in cats an average of 17.0 months before serum creatinine (Cr) concentrations increased above the reference interval.ObjectivesTo report on the utility of measuring serum SDMA concentrations in dogs for detection of CKD before diagnosis by measurement of serum Cr.Animals CKD dogs (n = 19) included those persistently azotemic for ≥3 months (n = 5), dogs that were azotemic at the time of death (n = 4), and nonazotemic dogs (n = 10). CKD dogs were compared with healthy control dogs (n = 20).MethodsRetrospective study, whereby serum Cr concentrations were determined by enzymatic colorimetry and serum SDMA concentrations were determined by liquid chromatography‐mass spectrometry in dogs with necropsy confirmed CKD.ResultsSerum SDMA increased before serum Cr in 17 of 19 dogs (mean, 9.8 months; range, 2.2–27.0 months). Duration of elevations in serum SDMA concentrations before the dog developed azotemia (N = 1) or before the dog died (N = 1) was not determined. Serum SDMA and Cr concentrations were linearly related (r = 0.84; P < .001). Serum SDMA (r = −0.80) and serum Cr (r = −0.89) concentrations were significantly related to glomerular filtration rate (both P < .001).Conclusion and Clinical ImportanceUsing serum SDMA as a biomarker for CKD allows earlier detection of kidney dysfunction in dogs than does measurement of serum Cr. Earlier detection might be desirable for initiating renoprotective interventions that slow progression of kidney disease.
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