Abstract 3633: Asymmetric Dimethylarginine (ADMA) Seems to be Mainly Dependent of Dimethylarginine Dimethylaminohidrolase (DDAH) and is not Associated with Vascular Damage in Chronic Dialysis Patients
Introduction: Asymmetric dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been considered as a risk factor for endothelial dysfunction and atherosclerosis, factors present in dialysis patients. ADMA level is expected to increase in renal failure mainly due to decreased excretion. The aim of our study was to evaluate the regulatory role of dimethylarginine dimethylaminohidrolase (DDAH) in synthesis of NO, and its relationship with atherosclerotic vascular clinical manifestations and inflammatory risk.
Material and methods: We measured serum activity of DDAH, eNOS, levels of ADMA, NO, homocysteine and TNF-α in 83 patients (M:56; F:27), aged 65±13 y, on high flux dialysis for 62±61 months. Renal failure was due to chronic GN (18), diabetes (23), hypertension (16), interstitial nephritis (10), PKD (8), others (8). Detection of L-citruline formation for determination of the enzymatic activity of DDAH and eNOS in erythrocyte was performed by spectrophotometry. Homocysteine was determined by
HPLC, NO by Griesse reagent, ADMA, 8-iso-PGF2α and TNF-α by ELISA. Patients were divided according the localization of vascular damage:
coronary disease and
Results: All patients had an increase in DDAH activity, compared with healthy controls (0.17±0.19 vs 0.09±0.07 μmol L-cit mg Hb−1 min−1; p=.05). ADMA levels were unexpectedly normal (0.33±0.41 μmol /L). The eNOS in patients was not different from healthy controls (0.19±0.28 vs 0.13±0.16 μmol L-cit mg Hb−1 min−1), although it was significantly increased, compared with patients without vascular damage, in groups A (0,41±0,41 vs 0,12±0,12; p=.02), B (0,24±0,32; p=.05) and C (0,23±0,32; p=.03). Age and isoprostane level were consistently associated with the presence of vascular disease. NO, TNF-α and homocysteine levels, were respectively 67±29 μM, 11±4 pg/ml and 3.2±1.7 mg/dl. There was a significant correlation between DDAH and eNOS activity (r=.25; p=.03), DDAH and TNF-α (r=.29; p=.01), and DDAH and homocysteine (r=.24; p=.04)
Conclusions: In dialysis patients, regulatory effect of DDAH over ADMA seems to be preponderant and is associated with inflammatory parameters. Although increased, eNOS did not seem protect patients from vascular damage.