Serum Symmetric Dimethylarginine Concentrations Research Articles

Incidence of all-cause and cardiovascular mortality predicted by symmetric dimethylarginine in the population-based study of health in pomerania.

BackgroundL-Arginine and its dimethylated derivatives asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) have been associated with cardiovascular (CV) and all-cause mortality in populations at risk. The present study aimed to investigate the prognostic value of L-arginine and its derivatives in the general population.Methods and ResultsWe evaluated 3,952 individuals (1,936 men and 2,016 women) aged 20–81 (median (IQR) 51 (37; 64) years) from the population-based Study of Health in Pomerania (SHIP). Associations of continuous [per standard deviation (SD) increase] and categorized (age- and sex-specific tertiles) serum L-arginine, ADMA, and SDMA concentrations with all-cause and cause-specific mortality were analysed. During a median (IQR) follow-up period of 10.1 (9.3; 10.8) years (38,476 person-years), 426 deaths (10.8%) were observed, including 139 CV deaths (3.5%), and 150 cancer deaths (3.8%). After multivariable adjustment, we revealed a positive association of SDMA with all-cause [hazard ratio (HR) per SD increase: 1.16, 95% confidence interval (CI): 1.07–1.25] and CV mortality [HR: 1.19, 95% CI: 1.05–1.35]. In contrast, we did not observe any association of SDMA with cancer mortality. Neither L-arginine nor ADMA were associated with all-cause or CV mortality.ConclusionSDMA, but not ADMA, is an independent predictor of all-cause and CV mortality in a large population-based cohort of European ancestry.

Transsulfuration Pathway Thiols and Methylated Arginines: The Hunter Community Study

BackgroundSerum homocysteine, when studied singly, has been reported to be positively associated both with the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine [ADMA, via inhibition of dimethylarginine dimethylaminohydrolase (DDAH) activity] and with symmetric dimethylarginine (SDMA). We investigated combined associations between transsulfuration pathway thiols, including homocysteine, and serum ADMA and SDMA concentrations at population level.MethodsData on clinical and demographic characteristics, medication exposure, C-reactive protein, serum ADMA and SDMA (LC-MS/MS), and thiols (homocysteine, cysteine, taurine, glutamylcysteine, total glutathione, and cysteinylglycine; capillary electrophoresis) were collected from a sample of the Hunter Community Study on human ageing [n = 498, median age (IQR) = 64 (60–70) years].ResultsRegression analysis showed that: a) age (P = 0.001), gender (P = 0.03), lower estimated glomerular filtration rate (eGFR, P = 0.08), body mass index (P = 0.008), treatment with beta-blockers (P = 0.03), homocysteine (P = 0.02), and glutamylcysteine (P = 0.003) were independently associated with higher ADMA concentrations; and b) age (P = 0.001), absence of diabetes (P = 0.001), lower body mass index (P = 0.01), lower eGFR (P<0.001), cysteine (P = 0.007), and glutamylcysteine (P<0.001) were independently associated with higher SDMA concentrations. No significant associations were observed between methylated arginines and either glutathione or taurine concentrations.ConclusionsAfter adjusting for clinical, demographic, biochemical, and pharmacological confounders the combined assessment of transsulfuration pathway thiols shows that glutamylcysteine has the strongest and positive independent associations with ADMA and SDMA. Whether this reflects a direct effect of glutamylcysteine on DDAH activity (for ADMA) and/or cationic amino acid transport requires further investigations.

Diagnostic value of plasma asymmetric and symmetric dimethylarginine levels in liver transplant recipients

Nitric oxide is an important factor in the pathogenesis of liver cirrhosis. Its synthesis depends on the availability of L‑arginine and is inhibited by asymmetric dimethylarginine (ADMA). Symmetric dimethylarginine (SDMA) seems to be a good marker of multiorgan failure, especially renal failure. The aim of the present study was to evaluate the diagnostic significance of dimethylarginines in patients after liver transplantation. The study included 30 cadaver liver donors and 30 recipients with liver cirrhosis. The following parameters were estimated in donors and in liver recipients before and at days 1 and 3 after transplantation: serum alanine transaminase (ALT), aspartate transaminase (AST), and γ‑glutamyltranspeptidase (GGT) activity, international normalized ratio (INR), concentrations of bilirubin, albumin, creatinine, electrolytes, ADMA, SDMA, and L‑arginine. Before transplantation cirrhotic patients showed higher bilirubin concentrations, higher ALT and GGT activity, and lower sodium and albumin levels compared with donors. At day 3 after transplantation, we observed a significant increase in ALT, AST, creatinine, sodium, ADMA, SDMA, and L‑arginine, and a decrease in bilirubin levels. A significant positive correlation between SDMA and creatinine was found in donors (P <0.001), recipients before transplantation (P <0.0005), and at days 1 (P <0.004) and 2 after transplantation (P <0.0005). A significant positive correlation was also observed before transplantation between ADMA and bilirubin concentrations (P = 0.0264), ADMA and albumin concentrations at day 1 after transplantation (P = 0.02), while a negative correlation was observed between ADMA and INR before transplantation (P = 0.008) and at day 3 after transplantation (P = 0.03) in recipients. An increase in dimethylarginine levels after liver transplantation seems to be due not only to the dysfunction of the transplanted liver, but also to impaired kidney function caused by the surgery itself and/or the use of a nephrotoxic calcineurin inhibitor--tacrolimus. A significant correlation between serum creatinine and SDMA concentrations both in liver donors and recipients suggests that SDMA renal clearance may have diagnostic value to evaluate the glomerular filtration rate in these patients.

Diabetic Retinopathy Is Associated With Elevated Serum Asymmetric and Symmetric Dimethylarginines

OBJECTIVEAsymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and l-arginine directly influence nitric oxide production. Our objective was to test whether serum ADMA, SDMA, or l-arginine levels correlate with diabetic retinopathy subtype or severity.RESEARCH DESIGN AND METHODSA total of 162 subjects with type 1 diabetes and 343 with type 2 diabetes, of whom 329 subjects had no diabetic retinopathy, 27 had nonproliferative diabetic retinopathy (NPDR), 101 had proliferative diabetic retinopathy (PDR), and 107 had clinically significant macular edema (CSME), were recruited. Blinding diabetic retinopathy was defined as severe NPDR, PDR, or CSME. Serum ADMA, SDMA, and l-arginine concentrations were determined by mass spectroscopy.RESULTSIn multivariate analysis, blinding diabetic retinopathy, PDR, and nephropathy were associated with significantly increased serum levels of ADMA (P < 0.001), SDMA (P < 0.001), and l-arginine (P = 0.001). Elevated ADMA (P < 0.001) and SDMA (P < 0.001) were also significantly associated with CSME.CONCLUSIONSSevere forms of diabetic retinopathy are associated with elevated serum ADMA, SDMA, and l-arginine. Further investigation is required to determine whether these findings are of clinical relevance.

Dimethylarginines in chronic renal failure

Background—Nitric oxide (NO) is a potent chemical mediator involved in many functions. In vivo production of NO is thought to be regulated by endogenous analogues of L-arginine: asymmetric dimethylarginine (ADMA)....