ADMA AS AN ENDOTHELIAL BIOMARKER: DOES IT PREDICT VASCULAR ACCESS DYSFUNCTION IN HEMODIALYSIS PATIENTS?

Vascular access (VA) is a critical component of chronic hemodialysis (HD). Failure of either an arteriovenous fistula (AVF) or a tunneled central venous catheter (tCVC) reduces dialysis adequacy, increases morbidity and mortality, and adds substantial healthcare costs. A central mechanism of access failure is endothelial injury leading to venous stenosis and thrombosis. Asymmetric Dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), the enzyme responsible for producing nitric oxide (NO) a key molecule that maintains endothelial function and vasodilation. Elevated ADMA levels reduce NO bioavailability, resulting in endothelial dysfunction, vasoconstriction, neointimal hyperplasia, and a higher risk of thrombosis. In patients with kidney failure, ADMA clearance is impaired because of decreased activity of dimethylarginine dimethylaminohydrolase (DDAH) the main enzyme that metabolizes ADMA as well as reduced renal excretion, leading to its accumulation in the circulation. Systemic inflammation and oxidative stress, common in HD patients, further suppress DDAH activity through pro-inflammatory cytokines and increased reactive oxygen and nitrogen species. Consequently, ADMA levels rise, worsening endothelial dysfunction. Numerous studies have linked elevated ADMA concentrations to cardiovascular events, atherosclerosis, and vascular injury in chronic kidney disease. These mechanisms are directly relevant to the pathogenesis of dialysis access failure characterized by stenosis or thrombosis. Although the biological role of ADMA is well established, clinical evidence supporting its use as a predictor of vascular access failure remains inconsistent. Therefore, investigating the association between plasma ADMA levels and vascular access failure in chronic HD patients is essential to clarify its diagnostic and prognostic value and to explore its potential as a biomarker for risk stratification and preventive vascular interventions.

This analytical cross-sectional study was conducted at the Hemodialysis Unit of Dr. Cipto Mangunkusumo National General Hospital, Jakarta, between June and August 2025. Adults aged 18 years or older who had undergone chronic hemodialysis for at least three months, with a minimum frequency of two sessions per week and using either an arteriovenous fistula (AVF) or a tunneled central venous catheter (tCVC) as vascular access, were eligible. Patients were excluded if they had an active infection or fever ≥38 °C within the previous month, recent antibiotic use, current immunosuppressant therapy, high-dose corticosteroid use, a diagnosis of malignancy, or if they declined participation. Demographic data, comorbidities, and dialysis access type were obtained from interviews and medical records, and venous blood samples were collected before dialysis session. Plasma Asymmetric Dimethylarginine (ADMA) levels were measured using the enzyme-linked immunosorbent assay (ELISA) method. Vascular access failure was defined according to the 2019 Kidney Disease Outcomes Quality Initiative (KDOQI) criteria as either current dysfunction identified at the time of assessment or a documented history of access failure. Differences in median ADMA levels among patients with current access failure, prior failure, and no failure were analyzed using the Mann–Whitney U test, with a p-value <0.05 considered statistically significant.

In this cross-sectional study of 80 chronic hemodialysis patients, the overall prevalence of vascular access failure was 81.25%. Median plasma ADMA concentrations showed no significant differences among groups: patients with current access failure had a median level of 110 µmol/L (IQR 91.75–121), those with a history of failure 100 µmol/L (IQR 91–118.75), and those without failure 103 µmol/L (IQR 89–123.75). Statistical comparison using the Mann–Whitney U test demonstrated no significant association between ADMA levels and vascular access failure (p = 0.947). 

In this cross-sectional study of chronic hemodialysis patients, plasma Asymmetric Dimethylarginine (ADMA) levels were not associated with vascular access failure. Median ADMA concentrations were similar across patients with current access failure, prior failure, and no failure, and statistical analysis showed no significant relationship. Although ADMA is mechanistically linked to endothelial dysfunction, these findings indicate that ADMA is not a useful standalone biomarker for predicting vascular access failure in this population.