In patients with progressively deteriorating renal function secondary to CAN, addition of MMF followed by withdrawal of CsA results in a significant improvement in transplant function without the risk of acute rejection.

Registry data show that there is an overall 3-5-fold increase in cancer risk in transplant recipients compared with the general population, with skin cancers and lymphoma particularly prevalent. Cancers in transplant recipients are often more aggressive than those in the general population, with poor prognosis, particularly for gastrointestinal tumours and lymphomas. Risk factors for post-transplant malignancy include factors common to the general population, such as increasing age, cigarette smoking and sun exposure. In addition, immunosuppression is an important factor in the development of post-transplantation cancer, although data for individual agents are not definitive. A number of studies have demonstrated that ciclosporin is associated with an increased risk of malignancy, whereas a few studies report no increase in risk of cancer after the introduction of ciclosporin into treatment regimens. Similarly, studies have shown that the mycophenolic acid-based agent mycophenolate mofetil is associated with an increased risk of malignancy, whereas other studies have demonstrated that mycophenolate mofetil is in fact associated with a lower risk. Polyclonal anti-thymocyte antibodies used for induction therapy appear to be related to an increased incidence of post-transplant lymphoproliferative disorder, but this effect is not observed with monoclonal anti-interleukin 2 antibodies. Azathioprine has been implicated in the development of skin tumours, possibly as a result of increased photosensitivity to ultraviolet light. The proliferation signal inhibitors appear to be associated with a reduced risk of some malignancies. Further research will elucidate the role of these newer immunosuppressive agents in post-transplantation malignancies.

The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.

Rapamycin is a new immunosuppressive agent approved for maintenance therapy after kidney transplantation. It may allow calcineurin-inhibitor-free, non-nephrotoxic immunosuppression. We report, however, on four kidney-transplant recipients who developed post-transplantation glomerulonephritis after conversion from a calcineurin-inhibitor-based immunosuppression to rapamycin. In all four patients nephrotic-range proteinuria occurred 2-9 months after conversion to rapamycin. Renal biopsy confirmed membrano-proliferative glomerulonephritis type 1 in one case, membranous glomerulonephritis in another and IgA-nephropathy in two cases, respectively. Calcineurin-inhibitor-based immunosuppression was reintroduced and resulted in complete remission of proteinuria and in stabilised renal function in all patients. We conclude that in the case of rapamycin-associated post-transplantation glomerulonephritis an attempt should be made to replace rapamycin by a calcineurin inhibitor.

SUMMARYModulation of proliferative T-cell responses by n-butyrate has been suggested to result from direct interference with cell cycle progression. Considering the important role of antigen-presenting cells (APC ) in T-cell activation, we were particularly interested in studying the impact of n-butyrate on these cells. We demonstrated that pretreatment of human peripheral blood mononuclear cells (PBMC) or monocytes with this agent resulted in a dose-and time-dependent downregulation of their capability to stimulate T-cell responses with a similar pattern of inhibition when this agent was present throughout the culture period. Pretreatment with n-butyrate was effective in preventing both alloresponses and T-cell proliferation to immobilized anti-CD3 monoclonal antibody (mAb) suggesting alteration of costimulatory function. Flow cytometric analysis revealed that interferon-c (IFN-c)-induced upregulation of B7-1 expression on monocytes was profoundly inhibited by nbutyrate. Furthermore, this agent significantly suppressed the expression of intercellular adhesion molecule-1 ( ICAM-1) or lymphocyte function-associated antigen-3 ( LFA-3). In contrast, constitutive as well as cytokine-induced expression of B7-2 was enhanced by n-butyrate. Additionally, in monocytes, but not in T cells, treatment with n-butyrate led to significant alteration of membrane integrity owing to apoptotic cell death. Our findings indicate that modulation of T-cell responses by n-butyrate could also result from altered APC function, possibly as a consequence of downregulating distinct adhesion and/or costimulatory receptors as well as of inducing apoptosis. A potential clinical relevance of short-chain fatty acids for reducing T-cell-mediated immune reactions via modulating APC function is speculated.