Mycophenolate mofetil combined with prednisone for diffuse proliferative lupus nephritis: a histopathological study

Abstract

Mycophenolate mofetil (MMF) is a potential new treatment for diffuse proliferative lupus nephritis. This study examines the clinical and histopathological effects, and potential mechanisms, of combination MMF/prednisone therapy in diffuse proliferative lupus nephritis. Nine patients with diffuse proliferative lupus nephritis confirmed by renal biopsy received MMF/prednisone for six months when repeat biopsies were performed. Clinical and histopathological parameters of activity and chronicity were studied. Collagens were detected by Sirus red staining; leucocyte phenotype, osteopontin (OPN), fibrinectin (FN), a-smooth muscle actin (a-SMA) and TGF-b1 were detected by immunohistochemistry. The changes of clinical and histopathologic parameters were assessed and compared to histopathologic indicators. Eight of the nine patients achieved clinical remission; renal function deteriorated in one. Histopathological activity indices reduced significantly (9.56 + 2.83 versus 5.22 + 1.86, P < 0.01); however, the chronicity indices did not change (3.56 + 1.42 versus 3.22 + 1.20). T-cell and monocyte/macrophage infiltration, OPN expression and the percentage of proliferative cells in both glomerulus and tubulo-interstitiumdecreased significantly. Other features of chronic lesions, except for glomerular collagen deposition, did not change. In conclusion, MMF/prednisone therapy was effective for our patients with proliferative lupus nephritis. The active inflammatory lesions could be ameliorated through reduction of lymphocyte and monocyte/macrophage infiltration, inhibition of cell proliferation and downregulation of adhesive molecules. However, the chronic fibrotic lesions could not be significantly reduced.