Original article
Clinical
Remission of Severe Relapsing or Persistent Lupus Nephritis Using Mycophenolate Mofetil

https://doi.org/10.1016/j.arcmed.2005.04.011Get rights and content

Background

The therapy of severe lupus nephritis (LN) consists of high-dose steroids and immunosuppressive agents, usually cyclophosphamide. Although effective in up to 90% of cases, this approach leads to undesirable complications in many cases. In recent years, mycophenolate mofetil (MMF), an immunosuppressive drug used in transplantation regimes, seems to be effective in selected cases of lupus nephritis.

Methods

In this report we present the results using MMF in seven cases of LN. MMF stabilized renal function, controlled extrarenal disease activity and led to less steroid dosing.

Results

Three patients achieved complete remission, two partial remissions and two failed, although these two patients were the ones with the highest chronicity indices in the renal biopsies. However, they were able to maintain stable renal function for more than one year with tolerable side effects. In two more patients the latter were mild and did not require either hospitalization or intense therapy.

Conclusions

MMF can be an option for selected cases with severe relapsing or persistent LN and can lead to induction of remission. This observation needs to be expanded. Larger randomized controlled studies are needed to evaluate its indication in earlier cases as induction of de novo disease and/or effective remission maintenance.

Introduction

The therapy of severe lupus nephritis (LN), mainly that of proliferative glomerulonephritis or membranous glomerulonephritis with proliferative changes (classes IV or Vb of the WHO), usually consists of high-dose prednisone and cyclophosphamide as immunosuppressive drugs. The therapeutic protocol developed more than 20 years ago at the National Institutes of Health (NIH, Bethesda, MD) is the most usual one employed in this type of nephritis (1). However, some patients have persistent activity or after a period of remission they have relapsing disease, which leads them to receive additional courses of the same drugs. Although the efficacy of this scheme as compared to high-dose steroids is proven, the toxicity due to this therapy is high and morbidity and mortality account for permanent damage or even death (2).

Mycophenolate mofetil, an inhibitor of the de novo pathway of purine synthesis in lymphocytes (3), is a useful immunosuppressive that has broadened its indications from preventing transplant rejection (4) to its use in several autoimmune diseases including lupus nephritis (5). The actions of this drug are multiple and include selective depletion of both T and B lymphocytes, reduced expression of adhesion molecules, diminished expression of inducible nitric oxide synthase and reduced proliferation of mesangial cells 6, 7. In the first randomized study comparing it to cyclophosphamide as inductor of remission, the efficacy of MMF was comparable to the one using oral CYC, as well as the relapse rate, but with less toxicity when using MMF (8). An interim follow-up report, however, showed that MMF patients tended to relapse later at a higher rate than those treated with the usual scheme (9).

In this report, we present the first cases treated in our center with MMF as reinduction therapy in persistent or relapsing cases of LN. We also report on their follow-up after they stopped MMF due to inability to continue due to cost. As far as we know, this is the first formal report using MMF for LN in Latin America. Our population is comparable in terms of disease behavior to Afro-Americans, a subset of patients who are prone to a less favorable course. Therefore, we believe that this communication is especially interesting for Latin American centers that treat lupus patients.

Section snippets

Materials and Methods

From May 2000 to February 2002, seven Mexican mestizo LN patients presenting with relapsing or persistent LN (except for one patient, see below) in spite of adequate therapy or due to serious side effects with azathioprin or CYC (either oral or IV) were offered MMF as induction or reinduction therapy. All fulfilled the American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) (10). The characteristics of the patients are summarized in Table 1. The majority of

Results

Patient's demographic characteristics at the beginning of treatment are shown in Table 1. There were six females and one male, with a mean age at the inclusion of this study of 34 ± 11 years. Two patients did not have biopsy performed due to the above-mentioned reasons. Two patients had relapsing disease after being inactive, four had persistent disease in spite of adequate treatment and patient 6 had de novo renal disease. The mean time of disease evolution at the start of MMF was 82.7 ± 63.7

Discussion

In recent years, the awareness that CYC therapy for LN can be very toxic (2) has led to the search for different treatment options, both for induction of remission and its maintenance.

MMF is a prodrug that after conversion to the active compound, mycophenolic acid, exerts different actions leading to improvement of renal function both in animal models and patients. In a study of MMF as induction drug, patients who received it for 6 months at a maximal dose of 2 g qd had a similar outcome in

Acknowledgments

The author wants to thank Isabel Balderas, M.D. for her collaboration in the initial phase of the study. The author is also deeply indebted to Antonio Villa, M.D. for help with the statistical analysis, Roche Mexico, especially through Ms. Jaqueline Haces and Noé Soria, M.D. The Women's Volunteer Committee from the Instituto Nacional de Ciencias Médicas y Nutrición provided the MMF to the patients.

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