Asymmetrical dimethylarginine is associated with renal and cardiovascular outcomes and all-cause mortality in renal transplant recipients

Abstract

Increased plasma levels of asymmetric dimethylarginine (ADMA) are associated with endothelial dysfunction and predict the progression to dialysis and death in patients with chronic kidney disease. The effects of these increased ADMA levels in renal transplant recipients, however, are unknown. We used the data from ALERT, a randomized, double-blind, placebo-controlled study of the effect of fluvastatin on cardiovascular and renal outcomes in 2102 renal transplant recipients with stable graft function on enrollment. Patients who were initially randomized to fluvastatin or placebo in the 5- to 6-year trial were offered open-label fluvastatin in a 2-year extension of the original study. After adjustment for baseline values for established factors in this post hoc analysis, ADMA was found to be a significant risk factor for graft failure or doubling of serum creatinine (hazard ratio 2.78), major cardiac events (hazard ratio 2.61), cerebrovascular events (hazard ratio 6.63), and all-cause mortality (hazard ratio 4.87). In this trial extension, the number of end points increased with increasing quartiles of plasma ADMA levels. All end points were significantly increased in the fourth compared to the first quartile. Our study shows that elevated plasma levels of ADMA are associated with increased morbidity, mortality, and the deterioration of graft function in renal transplant recipients.

Dimethylarginines as Risk Markers of Atherosclerosis and Chronic Kidney Disease in Children with Nephrotic Syndrome

“…In contrast to many studies [1,11,[32][33][34][35], the outcomes of the current study show that in the relapse phase, ADMA was negatively correlated with cholesterolemia and triglyceridemia. There are several explanations for these controversial results.…”

“…Another significant cause of presumed high ADMA concentrations in these children is endothelial dysfunction due to biochemical disturbances and hypertension, which is commonly found. In children with NS, cardiovascular events, including myocardial infarction, may result from early atherosclerosis due to endothelial dysfunction [31,32]. The aim of this study was to ascertain whether ADMA may play a role as an early marker for atherosclerosis in children with NS.…”

“…Increases in ADMA concentration are common in endothelial dysfunction and atherosclerosis [7][8][9][10].…”

The Effects of Asymmetric Dimethylarginine (ADMA), Nitric Oxide (NO) and Homocysteine (Hcy) on Progression of Mild Chronic Kidney Disease (CKD): Relationship Between Clinical and Biochemical Parameters

“…In addition, it might influence NO and GFR levels and affect atherosclerosis formation. Several studies suggested that ADMA level can be an independent risk factor for progression of CKD (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Elevated ADMA reduces bioavailability of NO and induces endothelial dysfunction and may be involved in the pathophysiology of cardiovascular disease in CKD (8).…”

Asymmetric and symmetric dimethylarginine as risk markers for total mortality and cardiovascular outcomes: A systematic review and meta-analysis of prospective studies

“…[12] With respect to SDMA, initial studies did not find an association with adverse outcomes, [7,13,14] but some more recent studies reported positive associations with all-cause mortality or CVD. [11,15,16] Overall, prior studies on ADMA/SDMA and CVD or all-cause mortality were derived from many different study populations (general population, [15,17,18] patients with CVD, [9,11,19,20] renal diseases, [7,13,[21][22][23][24] diabetes, [25,26] or critically ill patients from intensive care unit,[27-29] respectively), differed in their methodological approaches (e.g. using types of samples (plasma vs. serum) or methods to determine the biomarker levels (HPLC vs. tandem mass spectroscopy vs. ELISA), or considered different confounders in their analysis.…”