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EFFECT OF INTRAVENOUS N-ACETYLCYSTEINE ON ASYMMETRIC DIMETHYLARGININE LEVELS DURING HAEMODIALYSIS
Mochammad Thaha1, Widodo1, Pranawa1, Mohammad Yogiantoro1, Yasuhiko Tomino2
1Division of Nephrology-Hypertension, Department of Internal Medicine - School of Medicine Airlangga University, Dr. Soetomo Hospital, Surabaya, Indonesia
2Division of Nephrology -Department of Internal Medicine, Juntendo University School of Medicine

INTRODUCTION
Chronic kidney disease (CKD) patients have high morbidity and mortality due to cardiovascular disease (CVD), which cannot be fully explained by classical CVD risk factors. Among the emerging CVD risk factors, oxidative stress is currently the focus of attention. Nitric oxide (NO) plays important role in the control of renal function and long-term regulation of blood pressure. One of the possible causes of NO deficiency in CKD is increased levels of circulating asymmetric dimethylarginine (ADMA) due to inhibition of dimethylarginine dimethylaminohydrolase 2 (DDAH 2), an enzyme that metabolize ADMA. Oxidative stress itself inhibits DDAH 2 activity. N-acetylcysteine (NAC) is a thiol molecule that has both direct and indirect antioxidant effects.

OBJECTIVE
To evaluate the effect of intravenous NAC on ADMA levels in stage 5 CKD patients during haemodialysis

METHODS
This study is a randomized double blind controlled trial, on stage 5 CKD patients with chronic haemodialysis, age 21-65 years old, haemoglobin >8 g/dL, serum albumin > 3 g/dL and interdialytic weight gain < 3 Kg. The treatment group (20 patients) received 5 g of NAC intravenously in 4 hours haemodialysis, while the placebo group (20 patients) received normal saline. Blood pressure and ADMA levels were measured before and after haemodialysis.

RESULTS
In the control and treatment groups, ADMA levels decreased significantly (from 1.1253 + 0.1797 mM to 0.8676 + 0.1449 mM, p<0.001 and 1.1522 + 0.1737 mM to 0.7844 + 0.1586 mM, p<0.001, respectively). When reduction of ADMA levels in both groups were compared, this study showed that intravenous administration of NAC during haemodialysis decreased ADMA levels more significantly than haemodialysis procedure alone (p<0.05).

Key words :
antioxidant, asymmetric dimethylarginine, chronic kidney disease, haemodialysis, n-acetylcysteine, oxidative stress

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