Mycophenolate mofetil in lupus glomerulonephritis

The optimal treatment of severe lupus nephritis is unclear. Regimens consisting of steroid and cyclophosphamide (CYC) appear to be most effective. However, up to 15% of patients are refractory to CYC treatment, and 30% to 50% of patients still develop end-stage renal disease. Moreover, infection and gonadal toxicity are major concerns of CYC use in patients of the reproductive age. More effective, but less toxic, regimens are needed. Mycophenolate mofetil (MMF) is a new immunosuppressive agent that selectively inhibits activated lymphocytes and renal mesangial cells. Experience with MMF in solid-organ transplantation has shown the safety of this drug and its superiority over azathioprine (AZA) in the prevention of acute graft rejection. Data from experimental models of immune-mediated glomerulonephritis, particularly lupus nephritis, have shown that MMF ameliorates autoimmune phenomena, retards renal damage, and improves outcome. Although the use of MMF in lupus nephritis is still in its preliminary stage, uncontrolled experience has confirmed its efficacy in patients with serious disease recalcitrant to conventional cytotoxic agents. Controlled studies, albeit small and lacking statistical power, have shown that MMF is as effective as CYC in the induction of renal remission in the short term. With the current dosage used in systemic lupus erythematosus, MMF appears to be well tolerated, with no serious toxicities reported. Significantly less ovarian toxicity compared with CYC is particularly attractive for the consideration of MMF in lupus nephritis. However, the lack of long-term efficacy data and comparative studies with standard CYC regimens is the major deterrent for the first-line use of MMF in high-risk patients at this juncture. (C) 2002 by the National Kidney Foundation, Inc.