Prospective Randomized Study of Azathioprine versus Cyclosporin in Live-Donor Kidney Transplantation

Abstract

A total of 112 recipients of haploidentical live-related donor kidney transplants were assigned randomly prior to transplantation to two groups of immunosuppressive treatment. The first group (54 patients) received the conventional immunotherapy of azathioprine (AZA) and prednisolone (P; AZA-P group). In the second group, 58 patients were given cyclosporin (Cs) and P (Cs-P group). All patients had previous third-party blood transfusions. The follow-up period ranged from 3 to 6 years (mean 50 ± 8 months) during which 13 patients (24%) in the AZA-P group and 6 (10%) in the Cs-P group were switched to the alternate immunotherapy (p > 0.05). Analysis of patient and graft survival along the follow-up period did not disclose significant differences between patients of the two groups. While the overall frequency of acute rejection episodes was not significantly different between the two treatment groups, the number of patients who had 2 or more rejection episodes was higher in the AZA-P group (p < 0.04). The mean serum creatinine levels were significantly higher in the Cs-P group than corresponding levels in the AZA-P group at 1,12 and 24 months after transplantation. We have concluded that at least 75% of the haploidentical human lymphocyte antigen mismatched live-related donor renal transplants can be maintained on AZA-P immunotherapy with a comparable degree of success to those treated with Cs-P. However, in at least 15% of patients with conventional immunotherapy, Cs could reverse ongoing rejections, and therefore, it can be considered as a rescue treatment in AZA-treated patients with steroid-resistant or ongoing rejections.

Characteristics of Long-Term Live-Donor Renal Allograft Survivors

“…Our immunosuppressive protocols have previously been described in detail [3, 4, 5]from 1970s till the 1990s. All patients, before 1983, received azathioprine (2–3 mg/kg/day) and prednisolone (2 mg/kg/day, with subsequent tapering of the dose till 0.5 mg/kg/day after 1 month).…”

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“…5 During the follow-up (50 ± 8 mo), patient and graft survival rates did not significantly differ between the 2 groups. Moreover, overall frequency of acute rejection episodes was not different, although the number of patients who experienced repeated rejections was higher in group 1, with mean serum creatinine levels markedly higher among the recipients in group 2.…”

“…8 The long-term results after 20 years reported that triple therapy patients experienced higher incidence of both chronic rejection and liver diseases ( Table 2). 9…”

Long-term results of a prospective randomized study comparing two immunosuppressive regimens, one with and one without CsA, in low-risk renal transplant recipients

“…In contrast, other reports showed improvement of long-term renal function after patients' conversion from a cyclosporine/steroid-based regimen to AZA/steroids or MMFlsteroids [17, 19, 22, 24, 321. Long-term results of randomized therapeutic protocols primarily devoid of CsA have been reported very rarely [8,181, because CsA rapidly became the cornerstone immunosuppressive drug for most centers in the past I Syears. Although CNI-free regimens, using some newly introduced drugs are currently under investigation [I I, 12, 231, the long-term tolerance and benefit of such strategies are not known.…”

“…Although many authors have analyzed the kidney graft outcome after CsA withdrawal [lo, 15,16,20,21,24,27,29,31,321, trials that do not include any CNIs are quite rare [8,181. Therefore, the real impact of CNIs on long-term graft outcome is difficult to assess.…”