Protective Effect of N-Acetylcysteine On Early Graft Outcomes After Living Kidney Transplantation in Patients Older Than 60 Years: A Randomized, Double-Blind Clinical Trial.

Abstract

Background and objectives: Delayed graft function (DGF) is associated with adverse long-term outcomes in elderly renal transplant recipients. Ischemia-reperfusion injury plays a crucial role in the development of DGF. This study evaluated the potential benefits of N-acetylcysteine on early graft outcome, as well as tubular cell injury measured by urinary biomarkers in the early post-transplant period. Patients and Methods: The study was a randomized interventional double blind with parallel assignment. Its primary purpose was prevention of delayed graft function in this special group of patients. Elderly primary living renal graft recipients with their age more than 60 were randomly assigned to treatment (NAC) or control group and prospectively evaluated for 90 days. Exclusion criteria were patients unwilling to participate in the study and those who were unable to drink N-acetylcysteine during the first 7 postoperative days(PO). Treatment group received N-acetylcysteine 600 mg twice daily orally from 0 to 7th PO. Renal function was determined at 7th, 15th, 30th, 60th and 90th PO. Graft function was evaluated by measuring of serum creatinine, estimation of creatinine clearance by Cokcroft- Gault formula and presence of dialysis free status by Kaplan-Meier actuarial curve of recipients free from dialysis after renal transplantation. Serum levels of thiobarbituric acid reactive substances (TBARS), which are markers of lipid peroxidation and oxidative stress, were determined using the thiobarbituric acid assay from 0-7th PO. Statistical analysis was performed using SPSS 16.0. Results: Twenty seven patients were randomly assigned to NAC (n=16) or placebo (n=11). The incidences of DGF, slow graft function, and immediate graft function did not significantly differ between the treatment and control groups (14.5% versus 17.2%, 15.0% versus16.2%, and 69.5% versus 66.6%, respectively; P=0.3). The groups had similar levels of the urinary biomarker neutrophil gelatinase-associated lipocalin at multiple times points soon after transplantation; urine volume during first 7 PO days and lastly creatinine clearance at 90 days PO. CONCLUSIONS: This study did not show any clinically demonstrable beneficial effects of NAC given orally during the early postoperative period in elderly transplant recipients in terms of reducing the incidence of DGF or improving the short-term allograft function.