Mycophenolate mofetil combined with prednisone for diffuse proliferative lupus nephritis: a histopathological study.
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), alpha-smooth muscle actin (alpha-SMA) and TGF-beta1 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-interstitium decreased 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.
Institute of Nephrology and Renal Unit of the First Hospital, Peking University, Beijing, PR China.
Lei
L
Ding
Minghui
M
Zhao
Wanzhong
W
Zou
Yuchun
Y
Liu
Haiyan
H
Wang
D000199:Actins / Q000032:analysis; D000293:Adolescent; D000328:Adult; D002908:Chronic Disease; D003094:Collagen / Q000032:analysis; D004359:Drug Therapy, Combination; D005260:Female; D005353:Fibronectins / Q000032:analysis; D005938:Glucocorticoids / Q000008:administration & dosage*; D006651:Histocytochemistry; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D053495:Osteopontin; D011241:Prednisone / Q000008:administration & dosage*; D012795:Sialoglycoproteins / Q000032:analysis
D000199:Actins; D005353:Fibronectins; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin; D003094:Collagen; D009173:Mycophenolic Acid; D011241:Prednisone