Effect of N-Acetylcysteine on Residual Renal Function in Chronic Hemodialysis Patients

Background Preserving residual renal function (RRF) has always been the primary clinical goal for every nephrologists managing patients with chronic kidney disease but not yet on dialysis. RRF in patients on dialysis has proven to be a consistent and powerful predictor of mortality. This is particularly evident for patients treated with peritoneal dialysis (PD): CANUSA study showed that only RRF but not dialysis dose has significant predictive power of mortality [1].

Interestingly, there have been very few studies that have examined the contribution of RRF to outcome in hemodialysis (HD) patients. This is particularly unfortunate because HD patients counts more than 90% of all dialysis population both in Israel and USA. A single study showed that persistence of RRF significantly improved patients' outcome [2].

Moreover, it is well known that RRF deteriorates more rapidly in HD patients than in PD patients [3]. Preservation of RRF remains an unresolved problem in dialysis patients.

The exact mechanism of rapid loss of RRF on HD is not fully understood. Several experimental and clinical studies showed that variety of vascular events and increased oxidative stress in dialysis patients may be due to inhibition of nitric oxide (NO) synthesis by ADMA (Asymmetric Dimethylarginine ), known to be endogenous inhibitor of NO synthetase [4]. ADMA may be significantly reduced by dialysis [5]. Metabolism of ADMA is primarily by the enzyme DDAH , which activity is decreased by inflammation, oxidative stress, diabetes mellitus and hypercholesterolemia [6].

Based on current knowledge, treatment aimed at reducing oxidative stress should decrease ADMA levels [6], and it is logical to suggest that such a therapy might help to preserve RRF in HD patients. In our opinion, it is worth to check an ability of antioxidant therapy to produce a favorable effect on RRF. One preliminary study on effect of antioxidant Vitamin E showed a small beneficial effect on ADMA in chronic kidney disease [7].