Use of mycophenolic acid in non-transplant renal diseases

Abstract

Mycophenolic acid (MPA) is a relatively new immuno-suppressive drug, used since the nineties for theprevention of rejection in kidney transplantation.MPA has not only proved effective in preventingrejection, being even superior to azathioprine, but alsoseems to cause less adverse effects than otherimmunosuppressive drugs [1]. Because of these favour-able experiences with MPA in renal transplantation,the drug is currently used in patients with liver, lungand bone marrow transplantation as well. Given itsfavourable profile, MPA has also been used inautoimmune diseases. Following many cases andopen series on the successful use of MPA, mostly inthe form of mycophenolate mofetil (MMF), in renal,rheumatological, gastrointestinal, ophthalmological,dermatological and neurological autoimmune diseases,the first controlled studies have been published or areunderway.MPA is the active metabolite of the two currentlyavailable formulations: mycophenolate mofetil (MMF,Cellcept ) and the slow release formulation enteric-coated mycophenolate sodium (EC-MPS, Myfortic ).The mode of action and the pharmacokinetics of MPAare elegantly described by Allison [2]. In short, MPA isa non-alkylating drug that suppresses the immuneresponse by inhibiting the proliferation of activatedlymphocytes. MPA blocks the enzyme inosine mono-phosphate dehydrogenase (IMPDH), which is essentialfor the de novo synthesis of the purine guanine, andthereby inhibits lymphocytes from proliferating. Whilelymphocytes depend completely on IMPDH forsynthesis of guanine, most other human cells useother pathways for this synthesis, and are therefore notor less affected by the anti-proliferative effect of MPA.In addition, MPA has anti-fibrotic effects, as reviewedby Eugui [3].Following oral ingestion, both MMF and EC-MPSare resorbed and hydrolysed to MPA, which isconjugated in the liver into inactive mycophenolicacid glucuronide before being almost completelycleared by the kidney. Altered pharmacokinetics inpatients with renal insufficiency might explain theincreased rate of adverse effects, which can bemanaged by decreasing the dose of MMF [4]. MPAis not substantially cleared by peritoneal or haemodial-ysis [4].We hereby review the clinical experience with MPAin the treatment of renal diseases.