Mycophenolate mofetil in chronic glomerular diseases.

Correspondence: Helena Sá [email protected] Hospital da Universidade de Coimbra. Praceta Mota Pinto 3000-075 Coimbra. Portugal INTRODUCTION Mycophenolate mofetil (MMF), the first pharmaceutical prodrug of mycophenolic acid (MPA) that received approval for human clinical use, has been utilised in solid organ transplantation since 1995, particularly in kidney transplantation. MMF launching occurred one hundred years after MPA discovery as a fermentation product of Penicillium Brevicompactum and related fungi in 1893. Since 2002, MMF is the more frequent immunosuppressant used in solid organ transplantation. In kidney transplantation the antimetabolite MMF assumed a very important role in immunosuppressive regimens, with 80% of end-stage renal patients receiving MMF at hospital discharge after kidney transplantation in EUA. The other prodrug of MPA, the enteric coated mycophenolate sodium (EC-MPAS), has been introduced in transplantation drug market in 2004. Clinical experience with this formulation is significantly lower than MMF, both in organ transplantation and other human autoimmune diseases, so we focus this review on the clinical use of MMF in kidney glomerular diseases other than kidney transplantation. There is clinical rationale in trying to profit from MMF properties to treat or arrest the progression of many chronic glomerular diseases. In fact MPA which selectively inhibits B and T lymphocyte proliferation acts as a blocker of the inosine monophosphate dehydrogenase enzyme of the de novo purine synthesis and is characterized by other properties that support its use in glomerular diseases that progress to ESRD. These mechanisms are the impairment of antigen presentation by dendritic cells, the suppression of monocyte recruitment and of the glycosylation of adhesion molecules, the inhibition of vascular smooth muscle cell proliferation and of cytokine induced nitric oxide production. Mycophenolate mofetil has also demonstrated synergistic effects with angiotensin II inhibitors (ACE or ARA) in retarding the progression of chronic renal diseases in experimental animal models. Although there is theoretical support to use MMF in chronic glomerular diseases, we have to wait for the conclusion of adequately powered long-term randomized and controlled clinical trials before it should receive approval for the treatment of chronic glomerular diseases. At present time, MMF use for treatment of renal diseases other than kidney transplantation is supported by evidence-based medicine. This review intends to be a comprehensive summary of the main MMF indications in chronic glomerular diseases based on clinical and laboratorial evidence nowadays. MMF indications in different kind of glomerular diseases are presented in decrescent schedule, according to the strength of the evidence of its benefit, as showed in schematic picture of figure 1.