The safety and efficacy of MMF in lupus nephritis: a pilot study

Abstract

Inducing and maintaining remission in patients with lupus nephritis may be difficult. Current treatments have significant toxicity. Mycophenolate mofetil (MMF) limits damage in murine models of lupus nephritis. We have assessed the efficacy and tolerability of MMF in the treatment of patients with long-standing or resistant lupus nephritis. We have treated 13 patients with biopsy proven lupus nephritis (two membranous nephropathy, four membranous nephropathy with super-imposed proliferative changes, seven with proliferative glomerulonephritis). All patients had relapsed on conventional treatment or there were pressing indications to minimise steroid dosage or avoid alkylating agents. Nine out of 13 were treated with MMF and prednisolone, 3=10 with MMF alone and 1=10 with MMF, prednisolone and cyclosporine. Thirteen patients were treated with MMF for up to 37 months (median 25 months). Three patients were withdrawn from MMF during the first 8 months of treatment. The remainder tolerated MMF (median dose 1 g/day). Serological improvements were observed in 9=13 and steroid dosage was reduced in 8=10 patients. Infections occurred in 3=13. One patient relapsed. MMF significantly reduced the rate of decline of renal function. MMF should be considered in the treatment of long-standing or resistant lupus nephritis. Controlled clinical trials are required to confirm these findings.

Keywords

Mycophenolate mofetil lupus nephritis systemic lupus erythematosus chronic renal failure immunosuppression

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References

Ponticelli C , Banfi G , Moroni G. Systemic lupus erythematosus (clinical). In: Cameron JS , Davison AM , Grunfeld J , Kerr DNS , Ritz E (eds). Oxford Textbook of Clinical Nephrology. Oxford University Press: Oxford , 1998, pp 935–959.

Gruppo Italiano per lo Studio della Nefrite Lupica . Lupus nephritis: prognostic factors and probability of maintaining life-supporting renal function 10 y after the diagnosis . Am J Kidney Dis 1992; 19: 473–479 .

Mathew TH for the Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group . A blinded, long-term, randomized multi-center study of mycophenolate mofetil in cadaveric renal transplantation. Results at three years . Transplantation 1998; 65: 1450–1454 .

Jayne DRW . Non transplant uses of Mycophenolate mofetil Curr Opin Nephrol Hypertens 1999; 8: 563–567 .

Corna D , Morigi M , Facchinetti D , Bertani T , Zoja C , Remuzzi G. Mycophenolate mofetil limits renal damage and prolongs life in murine lupus autoimmune disease . Kidney Int 1997; 51: 1583–1589 .

McMurray RW , Elbourne KB , Lagoo A , Lal S. Mycophenolate mofetil suppresses autoimmunity and mortality in the female NZB × NZW Fl mouse model of systemic lupus erythematosus . J Rheumatol 1988; 25: 2364–2370 .

Van Bruggen MC , Walgreen B , Rijke TP , Berden JH. Attenuation of murine lupus nephritis by mycophenolate mofetil . J Am Soc Nephrol 1998; 9: 1407–1415 .

Briggs WA , Choi MJ , Scheel PJ Jr. Successful mycophenolate mofetil treatment of glomerular disease . Am J Kidney Dis 1998; 31: 213–217 .

Glicklich D , Acharya A. Mycophenolate mofetil therapy for lupus nephritis refractory to intravenous cyclophosphamide . Am J Kidney Dis 1998; 32: 318–322 .

10.

Dooley MA , Cosio FG , Nachman PH et al. Mycophenolate mofetil therapy in lupus nephritis: clinical observations . J Am Soc Nephrol 1999; 10: 833–839 .

11.

Chan TM , Li FK , Tang CSO et al Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis . New Engl J Med 2000; 343: 1156–1162

12.

Churg J , Bernstein J , Glassock RJ. Lupus nephritis. In: Churg J , Bernstein J Glassock RJ (eds). Renal Diseases, Classification and Atlas of Glomerular Diseases. Igaku-Shoin: New York , 1995, p 151-151.

13.

Vitali C , Bencivelli W , Isenberg DA , et al Disease activity in SLE: report of the Consensus Study Group of the European Workshop for Rheumatology Research II . Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE. Clin Exp Rheumatol 1992; 10: 541–547 .

14.

Austin HA , Klippel JH , Balow JE et al. Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs . New Engl J Med 1986; 314: 614–619 .

15.

Epinette WW , Parker CM , Jones EL , Greist MC.

Mycophenolic acid for psoriasis: a review of pharmacology, long term efficacy and safety

J Am Acad Dermatol 1987; 17: 962–971 .

16.

Briggs WA , Choi MJ , Scheel PJ Jr. Follow-up on mycophenolate mofetil treatment of glomerular disease . Am J Kidney Dis 1998; 31: 898–899 .

17.

Fujihara CK , Malheiros DM , Zatz R , Noronha ID. Mycophenolate mofetil attenuates renal injury in the rat remnant kidney . Kidney Int 1998; 54: 1510–1519 .

18.

Romero F , Rodriguez-Iturbe B , Parra G , Gonzalez L , Herrera-Acosta J , Tapia E. Mycophenolate mofetil prevents the progressive renal failure induced by 5=6 renal ablation in rats . Kidney Int 1999; 55: 945–955 .

19.

Allison AC , Kowalski WJ , Muller CJ , Waters RV , Eugui EM. Mycophenolate and brequinar, inhibitors of purine and pyrimidine synthesis, block the glycosylation of adhesion molecules . Transplant Proc 1993; 25(Suppl 2): 67–70 .

20.

Wang W , Mo S , Chan L. Mycophenolic acid inhibits PDGF-induced osteopontin expression in rat mesangial cells . Transplant Proc 1999; 31: 1176–1177 .

21.

Hauser IA , Renders L , Radeke HH , Sterzel RB , Goppelt-Struebe M. Mycophenolic mofetil inhibits rat and human mesangial cell proliferation by guanosine depletion Nephrol Dial Transplant 1999; 14: 58–63 .