Mycophenolate mofetil treatment for diffuse proliferative lupus nephritis: a multicenter clinical trial in China

To investigate the efficacy and side effects of mycophenolate mofetil (MMF) in the treatment of diffuse proliferative lupus nephritis( DPLN).

75 patients [13 male,62 female; age (31.0 +/- 10.1)y] with biopsy-proven active DPLN from nine hospitals in China from Jan. 1999 to Jan. 2000 were enrolled in this study, of whom 26 patients were refractory to conventional treatment of steroids and cyclophosphamide. 21 patients presented with relapses and 28 patients were newly diagnosed. All the patients were treated with a combined regimen of MMF and steroids. Patients who had severe active renal lesions were initially given intravenous methylprednisolone followed by oral prednisone. The initial dosage of MMF was 0.5 approximately 2.0 g/d and the administrati on maintained at least 6 months. 38 patients had repeat renal biopsy after treatment. SLE disease activity (SLE-DAI) score, renal active index (AI),chronic index(CI) and density of immunoglobulins, complement deposition was assessed before and after MMF treatment.

The mean starting dosage of MMF was (1.26 +/- 0.30) g/d, it was reduced to (1.21 +/- 0.30) g/d and (0.95 +/- 0.33) g/d at the end of the 3(rd) and 6(th) month respectively. The post-treatment Hb level increased from (92 +/- 21) g/L to (112 +/- 28) g/L(3 mo) and (116 +/- 21) g/L(6 mo), while proteinuria decreased from (4.24 +/- 2.66) g/d to (2.18 +/- 3.75) g/d (3 mos, P < 0.05) and (1.54 +/- 1.60) g/d( 6 mos,P < 0.01). Renal function impairment present in some of the patients also showed marked improvement. The proportion of patients with positive A-dsDNA antibody and hypocomplementemia was significantly reduced after 6 months of MMF treatment. SLE-DAI score in this group of patients decreased from (16.9 +/- 6.7) to (8.1 +/- 4.8) (P < 0.01) by the end of 3 months. Repeat renal biopsy in 38 patients 3 approximately 6 months after the treatment showed a significant decrement of AI ( 13.30 +/- 5.51) vs (3.38 +/- 1.98),P < 0.01, and an increment of CI (1.62 +/- 1.48) vs (2.62 +/- 1.85), P > 0.05. Immunoglobulins and complement deposition scores decreased from (9.39 +/- 3.51) to(6.71 +/- 3.16 ),P < 0.05. During the study period, 12 episodes of infection (16.0%) were recorded including pneumonia(2.7%), herpes zoster(8.0 %), urinary tract infection(2.7%), and tuberculosis(2.7%). Other side effects included gastrointestinal symptoms (10.7%), hirsutism(6.7%), leukocytopenia (1.3%) and transient elevation of SGPT(2.7%).

MMF in a dosage of 0.5 approximately 2.0 g/d combined with steroids is effective to control the lupus activity of DPLN and well tolerated by the patients.