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      Symmetric dimethylarginine concentrations in dogs with International Renal Interest Society stage 4 chronic kidney disease undergoing intermittent hemodialysis

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          Abstract

          Background

          Symmetric dimethylarginine (SDMA) is a methylated arginine derived from intranuclear methylation of l‐arginine by protein‐arginine methyltransferase and released into circulation after proteolysis. It is primarily eliminated by renal excretion, and its concentration is highly correlated with glomerular filtration rate (GFR) in animals and humans and is an earlier indicator of kidney dysfunction than serum creatinine concentration (sCr).

          Objectives

          To evaluate and quantify the effects of IV fluid therapy (IF) or intermittent hemodialysis (IH) on renal function in a randomized group of dogs previously diagnosed with International Renal Interest Society (IRIS) stage 4 chronic kidney disease (CKD).

          Animals

          Twenty‐four client‐owned dogs with naturally occurring CKD.

          Methods

          Serum from 14 dogs treated by IH and 10 dogs treated with IF was submitted for measurement of sCr and SDMA. Dogs in each treatment group received up to 5 treatment sessions, administered 48 hours apart.

          Results

          Significant differences ( P ≤ .05) were seen between treatment groups, but dogs from the IH group were the most affected based on SDMA ( P < .001), sCr ( P < .001), and blood urea ( P < .001) concentrations. Furthermore, for each 10% increase in urea reduction ratio, there was a 6.2 μg/dL decrease in SDMA ( P = .002).

          Conclusions and Clinical Importance

          Although SDMA is dialyzable biomarker and despite its removal by IH, SDMA correlates better with renal function than does sCr in dogs with CKD undergoing IF and IH.

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          Most cited references40

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          Catheter replacement of the needle in percutaneous arteriography; a new technique.

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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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              The role of asymmetric and symmetric dimethylarginines in renal disease.

              Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases. By inhibiting nitric oxide formation, ADMA causes endothelial dysfunction, vasoconstriction, elevation of blood pressure, and aggravation of experimental atherosclerosis. Levels of ADMA and its isomer symmetric dimethylarginine (SDMA), which does not inhibit nitric oxide synthesis, are both elevated in patients with kidney disease. Currently available data from prospective clinical trials in patients with chronic kidney disease suggest that ADMA is an independent marker of progression of renal dysfunction, vascular complications and death. High SDMA levels also negatively affect survival in populations at increased cardiovascular risk, but the mechanisms underlying this effect are currently only partly understood. Beyond glomerular filtration, other factors influence the plasma concentrations of ADMA and SDMA. Elevated plasma concentrations of these dimethylarginines might also indirectly influence the activity of nitric oxide synthases by inhibiting the uptake of cellular L-arginine. Other mechanisms may exist by which SDMA exerts its biological activity. The biochemical pathways that regulate ADMA and SDMA, and the pathways that transduce their biological function, could be targeted to treat renal disease in the future.
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                Author and article information

                Contributors
                tatiana.okamoto@unesp.br
                Journal
                J Vet Intern Med
                J. Vet. Intern. Med
                10.1111/(ISSN)1939-1676
                JVIM
                Journal of Veterinary Internal Medicine
                John Wiley & Sons, Inc (Hoboken, USA )
                0891-6640
                1939-1676
                12 September 2019
                Nov-Dec 2019
                : 33
                : 6 ( doiID: 10.1111/jvim.v33.6 )
                : 2635-2643
                Affiliations
                [ 1 ] Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science São Paulo State University—UNESP São Paulo Brazil
                [ 2 ] IDEXX Laboratories Inc Westbrook Maine
                Author notes
                [*] [* ] Correspondence

                Priscylla Tatiana Chalfun Guimarães‐Okamoto, Department of Veterinary Clinics, School of Veterinary Medicine and Animal Science, Rua Prof. Doutor Walter Mauricio Correa, s/n, Unesp Campus de Botucatu, 18618‐681 Botucatu, São Paulo, Brazil.

                Email: tatiana.okamoto@ 123456unesp.br

                Author information
                https://orcid.org/0000-0002-0420-7696
                Article
                JVIM15612
                10.1111/jvim.15612
                6872610
                31513317
                fe0c811e-d6fa-4168-a35b-4b69dd37afa3
                © 2019 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 http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 August 2018
                : 20 August 2019
                Page count
                Figures: 2, Tables: 3, Pages: 9, Words: 6387
                Categories
                Standard Article
                SMALL ANIMAL
                Standard Articles
                Nephrology/Urology
                Custom metadata
                2.0
                jvim15612
                November/December 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.7.2 mode:remove_FC converted:21.11.2019

                Veterinary medicine
                canine,dialysis,glomerular filtration rate,sdma renal biomarker
                Veterinary medicine
                canine, dialysis, glomerular filtration rate, sdma renal biomarker

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