Interleukin 2 Receptor Antagonists for Kidney Transplant Recipients

A Cochrane review [Abstract] 1 included 71 studies with a total of 10 520 subjects. Where interleukin 2 receptor antagonists (IL2Ra) were compared with placebo (32 trials, 5 854 patients) graft loss including death with a functioning graft was reduced by 25% at six months (RR 0.75, 95% CI 0.58 to 0.98,16 trials) and one year (RR 0.75, 95% CI 0.62 to 0.90, 24 trials), but not beyond this. Acute rejection (AR) was significantly reduced at one year (RR 0.72, 95% CI 0.64 to 0.81, 14 trials)) and there was a reduction in cytomegalovirus (CMV) infection (13 studies: RR 0.81, 95% CI 0.68 to 0.97, 13 trials). Where IL2Ra were compared with other antibody therapy no significant differences in treatment effects were demonstrated, but adverse effects strongly favoured IL2Ra. There were no significant differences in outcomes according to cyclosporine or tacrolimus use, azathioprine or mycophenolate, or to the study populations baseline risk for acute rejection. There is no apparent difference between basiliximab and daclizumab. IL2Ra are as effective as other antibody therapies and with significantly fewer side effects.

A retrospective analysis 2 evaluated a total of 206 patients who were switched to low-dose calcineurin inhibitors (CNI) + m-TORi or mycophenolate mofetil (MMF) + m-TORi treatment protocols in the first 3 months of renal transplantation.134 patients received anti-thymocyte globulin induction therapy. Initially, 108 patients were treated with cyclosporine and 98 were treated with tacrolimus-based regimens. 135 patients (65.5%) were switched to low-dose CNI + m-TORi and 71 patients (34.5%) were switched to MMF + m-TORi. The mean switching time was 3 months. At the end of the study, 161 patients (78.2%) were still continuing the m-TORi treatment protocol and 45 patients (21.8%) could not continue for various reasons (11.4% proteinuria, 5.5% edema, 2.9% acute rejection, 1% acne + oral aphthae, 1% neuropathy). The biopsy-proven acute rejection rate was 4.5% (n = 9). The mean duration of sustainability of m-TORi treatment protocol was 84.15 ± 6.79 months. Mean serum creatinine of patients who were still continuing m-TORi was 1.42 ± 1.09 mg/dL.

References

• Webster AC, Ruster LP, McGee R et al. Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst Rev 2010;2010(1):CD003897. [PubMed]
• Turunç V, Açikgöz SB, Dheir H. Early Switch to Mammalian Target of Rapamycin Inhibitors Is a Sustainable Treatment Approach in Renal Transplant Recipients: 7-Year Results. Transplant Proc 2019;51(4):1070-1073. [PubMed]