Mizoribine attenuates renal injury and macrophage infiltration in patients with severe lupus nephritis.

The purine synthesis inhibitor mizoribine (MZR) has been successfully used without serious adverse effects in the treatment of several renal diseases including lupus nephritis. Besides its immunosuppressive effects, MZR has recently been reported to ameliorate tubulointerstitial fibrosis in rats via suppression of macrophage infiltration. However, there has been little information regarding the beneficial effects of MZR from the histologic standpoint in human lupus nephritis. Pre- and posttreatment renal biopsy specimens obtained from nine patients with diffuse proliferative lupus nephritis (DPLN) were divided into two groups (group A, five patients who received immunosuppressive treatment with MZR and group B, four patients who received immunosuppressive treatment without MZR) and histologically evaluated. Grading was done according to the 2003 classification system for lupus nephritis developed by the International Society of Nephrology/Renal Pathology Society, which considers the activity and chronicity indices, an immunohistologic study to assess intraglomerular and interstitial infiltration by macrophages, and the expression of osteopontin. Although in all the patients the posttreatment renal biopsy showed improvement of histologic grading and activity indices, group A patients showed a significant decrease of the chronicity indices and of intraglomerular infiltration by macrophages when compared to group B patients (2.6 +/- 0.5 vs 4.0 +/- 1.4 and 0.5 +/- 0.2 vs 2.4 +/- 1.9 cells per glomerulus, respectively; p < 0.05). Although this was a preliminary study in a small number of subjects, these histological observations may further confirm the beneficial effects of MZR for selected patients with DPLN.