Plasma Asymmetric Dimethylarginine, Symmetric Dimethylarginine, <scp>l</scp>‐Arginine, and Nitrite/Nitrate Concentrations in Cats with Chronic Kidney Disease and Hypertension

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254

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.

Section: Discussionsupporting

confidence: 90%

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confidence: 74%

Section: Discussionmentioning

confidence: 99%

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Comparison of Serum Concentrations of Symmetric Dimethylarginine and Creatinine as Kidney Function Biomarkers in Cats with Chronic Kidney Disease

Hall

Yerramilli

Obare

et al. 2014

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254

“…Previous studies have demonstrated a strong relationship between serum SDMA and creatinine concentrations . Serum SDMA concentrations increase above normal when GFR decreases by approximately 40% below the normal rate, much earlier than the 75% decrease in GFR typically required for creatinine concentrations to increase above reference limits .…”

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confidence: 94%

Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism

Peterson

Fv²,

Rishniw

et al. 2018

BackgroundHyperthyroidism can complicate (mask) the diagnosis of chronic kidney disease (CKD) because it increases glomerular filtration rate and decreases body muscle mass, both of which can lower serum creatinine concentrations. Currently, there is no clinical test that can reliably predict which hyperthyroid cats have concurrent azotemic CKD that will become apparent after treatment of the hyperthyroidism.ObjectivesTo investigate serum symmetric dimethylarginine (SDMA) concentration as a potential marker of masked azotemia in untreated hyperthyroid cats.AnimalsTwo hundred and sixty‐two hyperthyroid cats and 206 aged‐matched, clinically normal cats.MethodsProspective study. We measured creatinine, urea nitrogen, SDMA, T4, and TSH concentrations before and 1, 3, and 6 months after treatment with radioiodine (131I) and classified 131I‐treated cats as azotemic or nonazotemic based on persistent, post‐treatment creatinine concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and diagnostic accuracy was determined by receiver operating characteristic analysis and logistic regression.ResultsNo hyperthyroid cats were azotemic before treatment, but 42 (16%) became azotemic when rechecked at 4–8 months (median, 6 months) after 131I treatment; of these, 14 had high SDMA concentrations before treatment. As a diagnostic test for pre‐azotemic (masked) CKD in untreated hyperthyroid cats, SDMA showed a sensitivity of 33.3% and specificity of 97.7%.Conclusions and Clinical ImportanceFinding a high serum SDMA concentration in a hyperthyroid cat can help predict development of azotemia after treatment. The test has high diagnostic test specificity (few false‐positive results) but relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats).

“…The cause has not been determined with certainty, but the effect may be endothelial dysfunction of which SDMA is believed to be a mediator . The vascular endothelium releases vasoactive substances such as nitric oxide (NO) which help maintain vascular integrity and regulate its homeostasis . Nitric oxide influences vascular tone, blood pressure, and regional blood flow while also having anti‐inflammatory, antithrombotic, and antiatherosclerotic effects .…”

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confidence: 99%

Symmetric Dimethylarginine in Cats with Hypertrophic Cardiomyopathy and Diabetes Mellitus

Langhorn

Kieler

Koch

et al. 2017

BackgroundSymmetric dimethylarginine (SDMA) has been increasingly used as a marker of early chronic kidney disease (CKD) in cats, but little is known about the influence of comorbidities on SDMA in this species.HypothesisHypertrophic cardiomyopathy (HCM) and diabetes mellitus (DM), independently of CKD, are associated with changes in serum SDMA.AnimalsNinety‐four cats (17 with CKD, 40 with HCM, 17 with DM, and 20 healthy controls).MethodsCase‐control study. Clinical examination, echocardiography, ECG, blood pressure, CBC, biochemistry, thyroxine, and SDMA measurement were performed. Urinalysis was performed in controls and cats with CKD and DM. Analysis of variance was used to compare overall differences in the log‐transformed SDMA data among groups. A random forest algorithm was applied to explore which clinical and other factors influenced serum SDMA.ResultsMedian (range) serum SDMA for the renal group (positive control) was 19 (10–93) μg/dL, whereas for the control group (negative control), it was 10 (5–15) μg/dL. For the cardiac and diabetic groups, serum SDMA was 9 (4–24) μg/dL and 7 (3–11) μg/dL, respectively. The renal group had significantly higher SDMA concentrations and the diabetic group significantly lower SDMA concentrations compared to all other groups.Conclusions and Clinical ImportanceSerum SDMA concentrations in cats with HCM were not significantly different from those of healthy control cats. Cats with DM, however, had significantly lower SDMA concentrations than controls, a finding that needs further investigation and should be kept in mind when evaluating renal function of cats with this endocrinopathy.