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

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          Abstract

          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 ( <  .001) and age ( =  .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 ( <  .001). LBM was affected by sex (males > females; =  .02). Mature adult dogs (<8 years) had greater LBM compared with geriatric dogs (≥8 years; <  .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.

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          Most cited references30

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          Arginine methylation an emerging regulator of protein function.

          Arginine methylation is now coming out of the shadows of protein phosphorylation and entering the mainstream, largely due to the identification of the family of enzymes that lay down this modification. In addition, modification-specific antibodies and proteomic approaches have facilitated the identification of an array of substrates for the protein arginine methyltransferases. This review describes recent insights into the molecular processes regulated by arginine methylation in normal and diseased cells.
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            Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C.

            For addressing the influence of muscle mass on serum and urinary creatinine and serum cystatin C, body composition was assessed by skinfold thickness measurement and bioelectrical impedance analyses. A total of 170 healthy individuals (92 women, 78 men) were classified as sedentary or with mild or moderate/intense physical activity. Blood, 24-h urine samples, and 24-h food recall were obtained from all individuals. Serum and urinary creatinine correlated significantly with body weight, but the level of correlation with lean mass was even greater. There was no significant correlation between body weight and lean mass with cystatin C. Individuals with moderate/intense physical activity presented significantly lower mean body mass index (23.1 +/- 2.5 versus 25.7 +/- 3.9 kg/m(2)) and higher lean mass (55.3 +/- 10.0 versus 48.5 +/- 10.4%), serum creatinine (1.04 +/- 0.12 versus 0.95 +/- 0.17 mg/dl), urinary creatinine (1437 +/- 471 versus 1231 +/- 430 mg/24 h), protein intake (1.4 +/- 0.6 versus 1.1 +/- 0.6 g/kg per d), and meat intake (0.7 +/- 0.3 versus 0.5 +/- 0.4 g/kg per d) than the sedentary individuals. Conversely, mean serum cystatin did not differ between these two groups. A multivariate analysis of covariance showed that lean mass was significantly related to serum and urinary creatinine but not with cystatin, even after adjustment for protein/meat intake and physical activity. Cystatin C may represent a more adequate alternative to assess renal function in individuals with higher muscle mass when mild kidney impairment is suspected.
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              Symmetric dimethylarginine (SDMA) as endogenous marker of renal function--a meta-analysis.

              Dosing of most drugs must be adapted in renal insufficiency, making accurate assessment of renal function essential in clinical medicine. Furthermore, even modest impairment of renal function has been recognized as a cardiovascular risk factor. The purpose of this analysis was to identify the role of symmetric dimethylarginine (SDMA), the structural isomer of the cardiovascular risk marker asymmetric dimethylarginine, as an endogenous marker of renal function. Comprehensive searches of Medline and the Cochrane Library from 1970 to February 2006 were performed to identify studies that evaluated the correlation between SDMA and renal function. The search was augmented by scanning references of identified articles and reviews. The correlation coefficients (R) were recorded from each study for the values of 1/SDMA and clearance estimates and for SDMA and creatinine levels. The summary correlation coefficients with 95% confidence intervals (CIs) were pooled using the random-effects method. In 18 studies involving 2136 patients systemic SDMA concentrations correlated highly with inulin clearance [R = 0.85 (CI 0.76-0.91, P < 0.0001)], as well as with various clearance estimates combined [R = 0.77 (CI 0.65-0.85, P < 0.0001)] and serum creatinine [R = 0.75 (CI 0.46-089, P < 0.0001)]. SDMA exhibits some properties of a reliable marker of renal function. Future studies have to clarify whether SDMA is indeed suited to improve diagnosis and eventually optimize care of patients.
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                Author and article information

                Journal
                J Vet Intern Med
                J. Vet. Intern. Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley and Sons Inc. (Hoboken )
                0891-6640
                1939-1676
                24 April 2015
                May-Jun 2015
                : 29
                : 3 ( doiID: 10.1111/jvim.2015.29.issue-3 )
                : 808-814
                Affiliations
                [ 1 ] Department of Biomedical Sciences College of Veterinary MedicineOregon State University Corvallis OR 97331‐4802
                [ 2 ] IDEXX Biotechnology GroupIDEXX Laboratories, Inc. Westbrook ME 04092
                [ 3 ] Pet Nutrition CenterHill's Pet Nutrition, Inc. Topeka KS 66617‐1587
                Author notes
                [*] [* ]Corresponding author: J. A. Hall, Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Dryden Hall 206, Corvallis, OR 97331‐4802; e‐mail : jean.hall@ 123456oregonstate.edu .
                Article
                JVIM12607
                10.1111/jvim.12607
                4895404
                25913398
                77b7c572-6912-459d-a0a8-81dbb0662018
                Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 23 September 2014
                : 19 February 2015
                : 31 March 2015
                Page count
                Pages: 7
                Funding
                Funded by: Pet Nutrition Center, Hill's Pet Nutrition, Inc
                Categories
                Standard Article
                Standard Articles
                Custom metadata
                2.0
                jvim12607
                May/June 2015
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.8.9 mode:remove_FC converted:06.05.2016

                Veterinary medicine
                canine,creatinine,symmetric dimethylarginine,urea nitrogen
                Veterinary medicine
                canine, creatinine, symmetric dimethylarginine, urea nitrogen

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