P734 Aims: The aim was to minimize nephrotoxicity and improve long term renal function in primary renal allograft recipients without adversely affecting efficacy. Methods: This 12 month open-label, multicenter, prospective study enrolled 536 patients who had received a first cadaveric or a living donor kidney. Patients were randomized in a 1:1:1 ratio before transplantation, between three treatment groups: Group A: MMF (2 g/day), daclizumab (5 doses given every other week with the first dose 2mg/kg and subsequent doses 1mg/kg), CS (corticosteroids), and low dose CsA (cyclosporine trough levels of 50-100ng/ml) given during the first 3 months posttransplant, followed by a 33% reduction per month from month 4, to complete withdrawal by month 7 Group B: MMF (2 g/day), daclizumab (as in Group A), CS, low dose CsA (trough levels of 50-100ng/ml) throughout the study Group C: MMF (2 g/day), CS, standard dose CsA (trough levels of 150-300ng/ml until month 4 posttransplant, and thereafter 100-200ng/ml) The primary end point was renal function by Glomerular Filtration Rate (GFR), measured with an exogenous substrate at 12 months posttransplant. Secondary end points included: GFR at 3 months, biopsy proven acute rejection (BPAR) at 6 and 12 months, patient and graft survival at 12 months, treatment failure, chronic allograft nephropathy, and serum creatinine and calculated creatinine clearance at 12 months. Results: Patients were enrolled from 32 sites in Australia, Canada, Europe, Mexico and the US. Demographics: 64% male, 83% Caucasian. Data are presented from the intent to treat population: 179 patients in Group A, 183 in Group B, and 173 in Group C. Primary endpoint: The mean GFR values at 12 month in ml/min/1.73m2 were: Group A=42.1 (SD=27.1 n=178) Group B=44.5 (SD=27.9 n=182) Group C=39.4 (SD=24.5 n=173) A protocol defined value of 10ml/min/1.73 m2 was imputed for missing values, and two outliers have been excluded (267.3 in Group A and 305 in Group B as they were clinically implausible). There were no statistically significant differences between the mean GFR values of the treatment groups. Selected Secondary endpoints: Proportion of patients experiencing first BPAR, graft loss and death:FigureEarly first BPAR, at 6 months, was lower in Groups A and B, who received daclizumab, compared with Group C, but it was not significantly different. At 12 months, the proportion of patients with first BPAR was significantly higher in Group A compared to Group B (p=0.018; Odds Ratio = 1.97; 95% confidence interval (CI) 1.23 to 3.16), but it was not different compared to Group C (p=0.098; Odds Ratio = 1.48; 95% CI 0.93 to 2.36). This increase in the number of patients with first BPAR in Group A between 6 and 12 months posttransplant occurred when CsA was withdrawn from the regimen. Such an increase was not seen in Groups B and C. No patients in Group B had a first BPAR during 6-12 months posttransplant. Conclusion: There was a trend towards improved GFR, with Group B (low dose CsA) being better than Group A (weaned from CsA), which was better than Group C (standard dose CsA), although this had not reached statistical significance at 12 months. CsA sparing with MMF, steroids and daclizumab induction is a clinically safe and effective immunosuppressive regimen. Standard dose CsA was not superior in preventing early or late acute rejection.
No takes yet. Share an insight, caveat, or question.
Ekberg et al. (2004) studied this question.