N-Acetylcysteine in hemodialysis diabetic patients resets the activation of NF-kB in lymphomonocytes to normal values.

BACKGROUND: Oxidative stress pathways are activated in diabetes, particularly when dialysis is required (DD). NF-kB is activated in this clinical condition. Since N-Acetyl-cysteine (NAC) is an anti-oxidant, we aimed at investigating its effect in modulating NF-kB activation in lymphomonocytes (PBMC) of DD patients. METHODS: Twenty-five DD patients were enrolled in a cross-over designed study. Tests were performed at T0 and after one month (T1) of treatment with NAC and three months after NAC withdrawal. We assessed NF-kB activation by EMSA, levels of advanced oxidation protein products (AOPP) by spectral analysis, total antioxidant capacity (TAC) by colorimetry, and apoptosis by FACS. RESULTS: At T0 a statistically significant increased activation of the subunits of NF-kB, p50/p65, was detected in PBMC of DD patients in comparison to controls (both P<.0001). After one month of NAC both p50-p50/p50-p65 dimers were significantly reduced (P<.004 and .006). Three months after drug withdrawal NF-kB increased again to basal levels (P<.002 and P<.001 vs. end of treatment with NAC). AOPP and TAC levels and the percentage of apoptotic PBMC revealed modifications in accordance with NFkB activation. In a multivariate linear regression model using delta AOPP as the dependent variable and delta p50-p50, delta TAC, and delta APO as independent variables, we found that all three dependent parameters all retained an independent correlation with delta AOPP. CONCLUSIONS: Our data indicate in vivo a modulation by NAC of parameters indicating a redox imbalance in DD patients on hemodialysis. The use of NAC might suggest a potential clinical benefit.

Effect of dialysis membrane biocompatibility on polymorphonuclear granulocyte activity in dialysis patients.

BACKGROUND: Among patients with defects of the phagocytic component of the immune system, chronic haemodialysis patients are highly susceptible to microbial infections characterized by high morbidity/mortality, related to an impairment of the phagocytic response. Therefore the potential influence of dialysis membrane biocompatibility on the activity of polymorphonuclear (PMN) granulocytes from dialysis patients was investigated in this study. METHODS: Nineteen patients in haemodialysis were included in the protocol and divided into two groups: a control group (7 patients) and a study group (12 patients). The study group patients were treated for subsequent periods of 1 month with different dialysis membranes: low flux excebrane E membrane (CL-E), low flux polysulfone (PS). The control group patients were treated with a low flux modified cellulose membrane (SMC) for the entire observation period. The aetiology of end-stage renal disease included glomerulonephritis, nephroangiosclerosis and interstitial nephropathy. Following each period of treatment, clinical and haematological parameters were evaluated; phagocytosis and microbicidal activity of PMNs from uraemic patients against Klebsiella pneumoniae, the pathogen which can pose severe problems in immune depressed patients, were investigated in parallel. RESULTS: The data evidence that both clinical and haematological parameters remained unchanged during the study period and no differences were found among treatments. On the contrary, the PMN activity varied according to the type of the membrane. In fact, the use of both PS and CL-E, in contrast to SMC, resulted in a PMN functionality similar to that observed in healthy subjects. CONCLUSIONS: These results provide evidence that the depressed PMN activities in dialysis patients may be influenced by membrane biocompatibility in such a way to be totally restored.