Adult chicken hens (Gallus gallus) have measurable circulating plasma symmetric dimethylarginine via liquid chromatography-tandem mass spectrometry.

OBJECTIVE: To investigate whether chickens (Gallus gallus) have measurable plasma symmetric dimethylarginine (SDMA) and to establish the diagnostic utility of the commercially available immunoassay (IA) for measurement of SDMA. ANIMALS: 245 chicken hens. METHODS: Blood samples were assessed for renal-focused biochemistry analytes. Plasma SDMA was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS/MS) and a high-throughput IA. A Passing-Bablok regression was used to compare the results of IA to LC-MS/MS/MS and reference intervals SDMA values were calculated. RESULTS: The reference interval for plasma SDMA measured by LC-MS/MS/MS is 5.58 to 10.62 µg/dL (range of values, 5 to 15 µg/dL). The concentration of SDMA measured by IA ranged from 1 to 12 µg/dL with a median of 7 µg/dL. Concentrations measured by SDMA-IA demonstrated a low correlation to the SDMA LC-MS/MS reference method. A Passing-Bablok linear regression analysis had a slope of 1.67 (95% CI, 1.35 to 2.14), an intercept of -5.76 (95% CI, -9.90 to -3.35), and a Kendall τ correlation of 0.39. CLINICAL RELEVANCE: SDMA circulates in chicken plasma and should be investigated as a potential renal biomarker in future studies. Because SDMA-IA exhibits a low correlation to the reference method (LC-MS/MS) future assessments of SDMA in chickens should utilize LC-MS/MS assays and compare them to the reference interval created here.

METHOD COMPARISON FOR MEASUREMENT OF SYMMETRIC DIMETHYLARGININE IN TIGERS (PANTHERA TIGRIS).

Renal disease is well documented in nondomestic felids and is monitored and diagnosed by serum concentration of blood urea nitrogen, creatinine, and phosphorous. Symmetric dimethylarginine (SDMA) has proven to be an earlier and more sensitive biomarker for the assessment of glomerular filtration rate. Although SDMA is commonly measured in nondomestic felids, information concerning the validity of the assay is lacking. The purpose of the study was to perform a method comparison between high-throughput immunoassay and the reference method, liquid chromatography-tandem mass spectrometry (LC-MS/MS), to quantify SDMA concentrations in tiger blood samples. Concentrations of SDMA were measured for 81 individual tiger samples. The SDMA immunoassay demonstrated excellent correlation to the LC-MS/MS reference method. A Passing and Bablok linear regression analysis had a slope of 1.03 (95% CI, 0.99-1.11), an intercept of 1.64 (95% CI, 0.46-2.34), and a Pearson R= 0.99. The mean bias was 1.53 µg/dl (95% CI, 0.63-2.42 µg/dl), and the limit of agreement was ±7.96 µg/dl. The degree of bias is within established acceptance criteria of 1-3 µg/dl for the immunoassay. Although this study provides good evidence of the utility of the immunoassay to measure SDMA in tiger serum and plasma, further assay validation is recommended.

Serum concentrations of symmetric dimethylarginine and creatinine in cats with kidney stones.

Serum concentrations of symmetric dimethylarginine (SDMA) correlate with renal function in cats and SDMA has been shown to be a more reliable and earlier marker for chronic kidney disease (CKD) compared with serum creatinine (Cr). Calcium oxalate uroliths tend to develop in mid-to-older aged cats and kidney stones may cause a reduction in renal function with increased SDMA, but normal serum Cr. The purpose of this retrospective study was to determine if cats with kidney stones had increased serum SDMA concentrations, and whether SDMA increased earlier than serum creatinine concentrations. Cats in the colony with kidney stones diagnosed between August 2010 and December 2015 (n = 43) were compared with healthy geriatric cats (n = 21) without kidney stones. Serum SDMA concentrations were determined by liquid chromatography-mass spectrometry and serum Cr concentrations were determined by enzymatic colorimetry. Cats with kidney stones were diagnosed antemortem by radiographic imaging (n = 12) or by postmortem necropsy (n = 31). Retrospectively, serum SDMA was found to be increased above the upper reference limit in 39 of 43 cats with kidney stones. Serum Cr was increased above the upper reference limit in 18 of 43 cats; 6 of these 18 cats had terminal azotemia only. The mean time that serum SDMA was increased before serum Cr was increased was 26.9 months (range 0 to 60 months). Kidney stones were composed of calcium oxalate in 30 of 34 cats. The lifespan for cats with kidney stones (mean, 12.5 years; range, 6.1 to 18.1 years) was shorter (P < 0.001) than for control cats (mean, 15.2 years; range, 13.0 to 17.2 years), suggesting that non-obstructive kidney stones have an effect on mortality rate or rate of CKD progression. In conclusion, if SDMA concentrations are elevated in mid-to-older aged cats, further imaging studies are warranted to check for the presence of kidney stones.

Positive Impact of Nutritional Interventions on Serum Symmetric Dimethylarginine and Creatinine Concentrations in Client-Owned Geriatric Dogs.

A prospective study was conducted in client-owned geriatric dogs to evaluate the short-term effects of a test food on serum symmetric dimethylarginine (SDMA) and creatinine (Cr) concentrations. Test food contained functional lipids (fish oil), antioxidants (lipoic acid, vitamins C and E), L-carnitine, botanicals (fruits and vegetables), controlled sodium concentration, and high quality protein sources (high bioavailability and an ideal amino acid composition). Dogs (n = 210) were fed either test food or owner's-choice foods (non-nutritionally controlled cohort). Dogs were included based on age and body weight: small (6.8 to 11.4 kg) and medium dogs (11.5 to 22.7 kg) were ≥ 9 years, whereas dogs >22.7 kg were ≥ 7 years at baseline. At baseline, all dogs had to have serum Cr concentrations within the reference interval and be free of chronic disease. Renal function biomarkers and urinalysis results at baseline, and after consuming test food or owner's-choice foods for 3 and 6 months, were evaluated. Only dogs consuming test food showed significant decreases in serum SDMA and Cr concentrations (both P ≤ 0.05) across time. At baseline or during the 6-month feeding trial, 18 dogs (8.6%) had increased serum SDMA, but normal serum Cr, consistent with IRIS Stage 1 chronic kidney disease. This included 9 dogs fed test food and 9 dogs fed owner's-choice foods. Compared with baseline, after feeding 9 dogs test food for 6 months, serum SDMA decreased in 8 dogs and increased in 1 dog. After feeding 9 dogs owner's-choice foods for 6 months, serum SDMA decreased in 4 dogs and increased in 4 dogs (remained stable in 1 dog). The decreases in serum SDMA and Cr concentrations were significant (both P = 0.03) only for dogs fed test food. These results suggest that nonazotemic dogs with elevated serum SDMA (early renal insufficiency) when fed a test food designed to promote healthy aging are more likely to demonstrate improved renal function compared with dogs fed owner's-choice foods.

Positive Impact of Nutritional Interventions on Serum Symmetric Dimethylarginine and Creatinine Concentrations in Client-Owned Geriatric Cats.

A prospective study was conducted in client-owned geriatric cats to evaluate the short- term effects of a test food on serum symmetric dimethylarginine (SDMA) and creatinine (Cr) concentrations. Test food contained functional lipids (fish oil), antioxidants (vitamins C and E), L-carnitine, botanicals (vegetables), highly bioavailable protein, and amino acid supplements. Cats (n = 80) were fed either test food or owner's-choice foods (non-nutritionally controlled cohort). Cats were included based on age (≥ 9 years), indoor only, neutered, and free of chronic disease. At baseline, all cats had serum Cr concentrations within the reference interval. Renal function biomarkers and urinalysis results at baseline and after consuming test food or owner's-choice foods for 3 and 6 months were evaluated. Cats consuming test food showed significant decreases in serum Cr and BUN concentrations across time. Overall, cats consuming owner's-choice foods showed significant increases in serum SDMA concentrations at 3 and 6 months compared with baseline (P ≤ 0.05), whereas in cats consuming test food serum SDMA concentrations did not change. At baseline or during the 6-month feeding trial, 23 (28.8%) cats had increased serum SDMA, but normal serum Cr consistent with IRIS Stage 1 chronic kidney disease. This included 6 cats fed test food and 17 cats fed owner's-choice foods. In the 6 cats fed test food, serum SDMA decreased in 3 cats and remained stable in 1 cat, whereas in the 17 cats fed owner's-choice foods, serum SDMA increased in 13 cats and decreased or remained stable in 4 cats. The increase in serum SDMA concentration was significant (P = 0.02) only for cats fed owner's-choice foods. These results suggest that nonazotemic cats with elevated serum SDMA (early renal insufficiency) when fed a food designed to promote healthy aging are more likely to demonstrate stable renal function compared with cats fed owner's-choice foods. Cats fed owner's-choice foods were more likely to demonstrate progressive renal insufficiency.

Relationship between lean body mass and serum renal biomarkers in healthy dogs.

BACKGROUND: Symmetric 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. HYPOTHESIS: Differences in lean body mass (LBM) influence sCr, but not serum SDMA concentrations. ANIMALS: Forty-one healthy Beagles, mean age 9.9 years (range: 3.1-14.8 years), were studied over a 6 month period. METHODS: Serum 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.