Use of mycophenolic acid in non-transplant renal diseases.

Mycophenolic acid (MPA) is a relatively new immunosuppressive drug, used since the nineties for the prevention of rejection in kidney transplantation. MPA has not only proved effective in preventing rejection, being even superior to azathioprine, but also seems to cause less adverse effects than other immunosuppressive drugs [1]. Because of these favourable experiences with MPA in renal transplantation, the drug is currently used in patients with liver, lung and bone marrow transplantation as well. Given its favourable profile, MPA has also been used in autoimmune diseases. Following many cases and open series on the successful use of MPA, mostly in the form of mycophenolate mofetil (MMF), in renal, rheumatological, gastrointestinal, ophthalmological, dermatological and neurological autoimmune diseases, the first controlled studies have been published or are underway. MPA is the active metabolite of the two currently available formulations: mycophenolate mofetil (MMF, Cellcept ) and the slow release formulation entericcoated mycophenolate sodium (EC-MPS, Myfortic ). The mode of action and the pharmacokinetics of MPA are elegantly described by Allison [2]. In short, MPA is a non-alkylating drug that suppresses the immune response by inhibiting the proliferation of activated lymphocytes. MPA blocks the enzyme inosine monophosphate dehydrogenase (IMPDH), which is essential for the de novo synthesis of the purine guanine, and thereby inhibits lymphocytes from proliferating. While lymphocytes depend completely on IMPDH for synthesis of guanine, most other human cells use other pathways for this synthesis, and are therefore not or less affected by the anti-proliferative effect of MPA. In addition, MPA has anti-fibrotic effects, as reviewed by Eugui [3]. Following oral ingestion, both MMF and EC-MPS are resorbed and hydrolysed to MPA, which is conjugated in the liver into inactive mycophenolic acid glucuronide before being almost completely cleared by the kidney. Altered pharmacokinetics in patients with renal insufficiency might explain the increased rate of adverse effects, which can be managed by decreasing the dose of MMF [4]. MPA is not substantially cleared by peritoneal or haemodialysis [4]. We hereby review the clinical experience with MPA in the treatment of renal diseases.