Asymmetric dimethylarginine (ADMA) and its enantiomer, Symmetric dimethylarginine (SDMA), are naturally occurring amino acids that were first isolated and characterized in human urine in 1970. ADMA is the most potent endogenous inhibitor of nitric oxide synthase (NOS), with higher levels in patients with end-stage renal disease (ESRD). ADMA has shown to be a significant predictor of cardiovascular outcome and mortality among dialysis patients. On the other hand, although initially SDMA was thought to be an innocuous molecule, we now know that it is an outstanding marker of renal function both in human and in animal models, with ESRD patients on dialysis showing the highest SDMA levels. Today, we know that ADMA and SDMA are not only uremic toxins but also independent risk markers for mortality and cardiovascular disease (CVD). In this review, we summarize the role of both ADMA and SDMA in chronic kidney disease along with other cardiovascular risk factors.

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Chronic Kidney Disease (CKD) and kidney failure is a global health problem associated with morbidity, mortality and health care costs with unequal access to kidney replacement therapy between countries. The diversity of guidelines concerning referral from primary care to a specialist nephrologist determine different outcomes around the world among patients with CKD where several guidelines recommend referral when the glomerular filtration rate (GFR) is < 30 mL/min/1.73 m2 regardless of age. Additionally, fixed non-age-adapted diagnostic criteria for CKD that do not distinguish correctly between normal kidney senescence and true kidney disease can lead over-diagnosis of CKD in elderly and under-diagnosis of CKD in young patients and contributes to unfair referral of CKD patients to a kidney specialist. Non-age adapted recommendations contributes to unnecessary referral in very elderly with mild disease where risk of death consistently exceeds the risk of progression to kidney failure and on the other hand ignore the possibility of effective interventions of young patient with long life expectancy. The opportunity of mitigating CKD progression and cardiovascular complications in young patients with early stages of CKD is a task entrusted to primary care providers which are possibly unable to accomplish optimally guideline-directed medical therapy for this purpose. The shortage in the nephrology workforce has classically leaded to focus referral on advanced CKD stages preparing kidney replacement, but the need for hasty referral to at nephrologist because of urgent requirement for kidney replacement therapy in advanced CKD is still observed and changes are required to move towards reducing the kidney failure burden. Kidney Failure Risk Equation (KFRE) and its potential value is a novel tool that can guide wiser nephrology referrals and impact patient volumes.

IntroductionChronic kidney disease is a major public health problem. In the last decade, it has been shown that the early stages of chronic kidney disease are associated with an inflammatory condition involving an increased risk of cardiovascular morbidity and long-term mortality. In patients with chronic kidney disease and more specifically those on hemodialysis, cardiovascular events are the most common cause of death. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and may be an independent risk factor for endothelial dysfunction and cardiovascular disease.MethodsWe performed a cross-sectional analysis to identify factors that were associated with ADMA such as certain medications related to cardiovascular disease in dialysis patients.ResultsPatients who were treated with paricalcitol had significantly lower levels of ADMA (0.21 ± 0.19 μmol/l) compared with those not treated with paricalcitol (0.42 ± 0.35 μmol/l) (P = 0.00027). Dividing ADMA levels by quartiles, patients treated with paricalcitol were less likely to have very high level ADMA (P = 0.014), whereas there were no significant differences with other medications. Higher dose of paricalcitol was also related to lower levels of ADMA noting an inverse correlation (r = –0.36, P = 0.013).DiscussionHemodialysis patients treated with paricalcitol presented significantly decreased ADMA levels compared with those who did not receive this treatment. Possible beneficial effects in terms of cardiovascular morbidity and mortality by paricalcitol and its association with ADMA and nitric oxide synthesis are unknown. Studies to confirm this effect and determine the underlying pathophysiological mechanism are necessary.