Renal transplant recipients have increased mortality rates when compared with the general population. The new immunosuppressive drugs have improved short-term patient survival up to 95% at 1–2 years, but these data have to be confirmed in long-term follow-up. Furthermore, no particular regimen has proved to be superior over others with regard to patient survival.

Immunosuppressive drugs in kidney transplantation: impact on patient survival, and incidence of cardiovascular disease, malignancy and infection.

BackgroundIn previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. MethodsWe randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). ResultsA total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all avail...

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Belatacept and Long-Term Outcomes in Kidney Transplantation.

Background. Mycophenolate Mofetil (MMF) has been shown to significantly decrease the number of acute rejection episodes in renal transplant recipients during the 1st year. A beneficial effect of MMF on long-term graft survival has been more difficult to demonstrate. This beneficial effect has not been detected, despite the impact of acute rejection on the development of chronic allograft nephropathy and experimental evidence that MMF may have a salutary effect on chronic allograft nephropathy independent of that of rejection. Methods. Data on 66,774 renal transplant recipients from the U.S. renal transplant scientific registry were analyzed. Patients who received a solitary renal transplant between October 1, 1988 and June 30, 1997 were studied. The Cox proportional hazard regression was used to estimate relevant risk factors. Kaplan-Meier analysis was performed for censored graft survival. Results. MMF decreased the relative risk for development of chronic allograft failure (CAF) by 27% (risk ratio [RR] 0.73, P<0.001). This effect was independent of its outcome on acute rejection. Censored graft survival using MMF versus azathioprine was significantly improved by Kaplan-Meier analysis at 4 years (85.6% v. 81.9%). The effect of an acute rejection episode on the risk of developing CAF seems to be increasing over time (RR51.9, 1988 ‐91; RR52.9, 1992‐94; RR53.7, 1995‐ 97). Conclusion. MMF therapy decreases the risk of developing CAF. This improvement is only partly caused by the decrease in the incidence of acute rejection observed with MMF; but, is also caused by an effect independent of acute rejection.

Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection.

Mycophenolate mofetil (MMF) is a relatively new immunosuppressive drug It inhibits inosine monophosphate dehydrogenase, a key enzyme in the de novo pathway of purine synthesis, and thus causes lymphocyte-selective immunosuppression Large clinical trials have revealed the efficacy of MMF in the prevention of allograft rejection when administered together with cyclosporin or tacrolimus and corticosteroids Although the adverse effect profile of MMF is comparatively benign, gastrointestinal adverse effects are a major concern These effects are partially explained by the increased immune suppression, by the mode of action and by interactions, particularly with other immunosuppressants The aetiology of the rarest gastrointestinal adverse effects is still not completely clear Therapy depends upon the clinical gravity of the adverse effects and is therefore a case of waiting and observing An adjustment of dosage of immunosuppressants according to the clinical situation and, particularly in the case of MMF, spreading the total dosage over more than 2 daily doses are often sufficient Should adverse effects persist for a longer period of time and be of a more serious nature, a comprehensive invasive diagnostic process is necessary, including endoscopy and biopsy and the search for opportunistic infections In this case, dosage reduction or the complete withdrawal of MMF seems to be unavoidable Severe gastrointestinal complications with MMF are rare, but when they do occur they may require extensive diagnosis and treatment In the future, therapeutic drug monitoring and, where necessary, pharmacological modifications of MMF could lead to a further reduction of adverse effects with an equal or even increased efficacy

Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management.

Post-transplant lymphoproliferative disorders (PTLD) are a recognized complication of the immunosuppression required to prevent allograft rejection, occurring in 1-20% of recipients of solid organ transplants. Several factors greatly increase the risk of developing PTLD early post-transplant in any individual recipient. Epstein-Barr virus (EBV) infection is critical in the pathogenesis of the majority of these cases. Pre-transplant EBV seronegativity increases the incidence of PTLD 10- to 75-fold over that of EBV-seropositive recipients. Other risk factors include very young recipient age, cytomegalovirus infection or mismatching (donor positive-recipient negative), aggressive immunosuppression with conventional biologic agents, and the type of organ transplanted. In contrast, the risk of developing PTLD late in the post-transplant course does not appear to be influenced by the type of immunosuppressive agents employed, but rather by the duration of any immunosuppression. The role of EBV in late PTLD is also less certain, as a greater proportion of lesions are not associated with evidence of EBV infection. As the understanding of these risk factors has expanded, opportunities exist to target those populations at highest risk for the development of PTLD for aggressive monitoring and pre-emptive or prophylactic therapy. It is hoped that implementation of such strategies will render early PTLD a preventable complication of transplantation.

Identifying the patient at risk for post-transplant lymphoproliferative disorder.

Mycophenolate mofetil in renal transplantation: 3-year results from the placebo-controlled trial.European mycophenolate mofetil study group.

M Rees

Papers

Mycophenolate mofetil in renal transplantation: 3-year results from the placebo-controlled trial