Key result
Higher plasma ADMA levels were significantly associated with increased all-cause mortality in renal transplant recipients, demonstrating a hazard ratio of 1.52 per standard deviation increase.
Cohort (n=686)
No
High levels of plasma ADMA are independently associated with increased all-cause mortality in stable renal transplant recipients, linking disturbed NO metabolism to patient survival.
Answers are grounded in this paper and cite their sources.
ADMA should not yet guide management in renal transplant recipients; leaves open whether targeting NO metabolism improves survival.
Asymmetric dimethylarginine (ADMA) is a key endogenous inhibitor of endothelial NO synthase that affects endothelial function, blood pressure and vascular remodeling. Increased plasma levels of ADMA are associated with worse outcome from cardiovascular disease. Due to endothelial dysfunction before and after kidney transplantation, renal transplant recipients (RTR) are at high risk for the alleged deleterious effects of ADMA. We investigated the associations of ADMA levels with all-cause mortality and graft failure in RTR. Plasma ADMA levels were determined in 686 stable outpatient RTR (57 % male, 53 ± 13 years), with a functioning graft for ≥1 year. Determinants of ADMA were evaluated with multivariate linear regression models. Associations between ADMA and mortality were assessed using multivariable Cox regression analyses. The strongest associations with plasma ADMA in the multivariable analyses were male gender, donor age, parathyroid hormone, NT-pro-BNP and use of calcium supplements. During a median follow-up of 3.1 [2.7-3.9] years, 79 (12 %) patients died and 45 (7 %) patients developed graft failure. ADMA was associated with increased all-cause mortality [HR 1.52 (95 % CI 1.26-1.83] per SD increase, P < 0.001], whereby associations remained upon adjustment for confounders. ADMA was associated with graft failure [HR 1.41 (1.08-1.83) per SD increase, P = 0.01]; however, upon addition of eGFR significance was lost. High levels of plasma ADMA are associated with increased mortality in RTR. Our findings connect disturbed NO metabolism with patient survival after kidney transplantation.
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Frenay et al. (2015) conducted a cohort in Renal transplant recipients (n=686). Plasma ADMA vs. Lower ADMA levels was evaluated on All-cause mortality (HR 1.52, 95% CI 1.26-1.83, p=<0.001). Higher plasma ADMA levels were significantly associated with increased all-cause mortality in renal transplant recipients, demonstrating a hazard ratio of 1.52 per standard deviation increase.
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