Benefit-risk assessment of ciclosporin withdrawal in renal transplant recipients.
Ciclosporin is associated with significant toxicity, including nephrotoxicity, and with an increased risk of cardiovascular events. Many attempts have been made to wean patients from ciclosporin. Before the availability of new immunosuppressive drugs, the acute rejection rate observed after ciclosporin withdrawal did not permit the widespread use of withdrawal regimens even though meta-analysis did not show that they adversely affected patient or graft survival. Nevertheless, maintenance therapy with azathioprine and corticosteroids has not become routine practice. The introduction of mycophenolate mofetil and subsequently sirolimus has increased the number of clinical studies of the effects of ciclosporin withdrawal. In stable patients, this withdrawal is associated with a small but significant increase in the incidence of acute rejection episodes. Declining renal function and other forms of ciclosporin-related toxicity have improved. However, this improvement was also observed when ciclosporin was only reduced (and not withdrawn), which did not increase the risk of acute rejection. More precise definition of the patients who could benefit from ciclosporin-withdrawal may help to optimise the immunosuppressive regimen in this setting. In patients with chronic allograft deterioration, ciclosporin withdrawal together with mycophenolate mofetil introduction has been shown to improve renal function significantly in many small studies, and a large prospective randomised study. For the time being, ciclosporin withdrawal is a good therapeutic option for patients with declining renal function and signs of chronic ciclosporin nephrotoxicity on renal biopsy. Finally, recent preliminary studies have reported the results of complete avoidance of calcineurin inhibitors after renal transplantation. These results are promising as regards the incidence of acute rejection, renal function and safety, but need confirmation in larger trials with a longer follow-up. Nevertheless, it has become clear that the concept of an immunosuppressive regimen with little or no nephrotoxicity after renal transplantation is more and more important and plays a crucial part in tailoring immunosuppression to the needs of specific patient populations.
Thervet
Eric
E
Service de Néphrologie et Transplantation Rénale, Hôpital Saint-Louis, Paris, France. eric.thervet@sls.ap-hop-paris.fr
Martinez
Frank
F
Legendre
Christophe
C
D016572:Cyclosporine / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation; D018570:Risk Assessment
D007166:Immunosuppressive Agents; D016572:Cyclosporine