Immunosuppressive Treatment of Membranoproliferative Glomerulonephritis

Abstract

The treatment of membranoproliferative glomerulonephritis (MPGN) is considered by most authors as unrewarding, and the disease progresses to end-stage renal disease (ESRD). We studied the effectiveness of a new immunosuppressive (IS) regimen by analyzing the rates of remission, relapse and progression to ESRD in 19 patients with MPGN. The treatment consisted of 4 phases: (1) induction with intravenous boluses of methylprednisolone plus cyclophosphamide (CPM) orally; (2) maintenance with oral prednisone (PDN) in an alternateday regimen and CPM in a daily oral dose; (3) tapering during which PDN alone was slowly decreased; (4) discontinuation when CPM was omitted and PDN slowly withdrawn according to the steroid withdrawal schedule. At the end of the treatment that lasted on average 10 ± 1 months, 15 patients remitted, 3 improved and 1 progressed. There were 8 relapses in 6 patients: 4 in 3 patients were treated with repeat cycles and remitted completely. Four patients who had relapsed after 4, 8,11 and 13 years of remission refused retreatment and progressed rapidly to ESRD. All patients treated and retreated after relapsing had remissions, while renal failure and disease progression occurred in 1 patient only. Plasma creatinine averaged, in the whole group, 165 ± 26 before, 156 ± 30 after treatment and 224 ± 57 μM/1 at the end of 7.4 ± 0.8 years of follow-up. An intensive IS regimen combining steroids and alkylating agents in high doses and for a prolonged time is effective in inducing remission and halting progression to ESRD in patients with MPGN.

Rosiglitazone decreases blood pressure and renal injury in a female mouse model of systemic lupus erythematosus

“…Renal inflammation is linked to the development of hypertension in experimental models through the promotion of renal injury (7,20). Indeed, several studies report that anti-inflammatory or immunosuppressive therapies, such as corticosteroids, mycophenalate mofetil, or cyclophosphamide can reduce urinary albumin in humans or animal models with SLE (11,12,21,30). However, the potential for anti-inflammatory therapies in SLE hypertension has not been previously examined.…”

Update on Membranoproliferative GN

“…For severe disease, immunosuppressive therapy is indicated. Although prednisone and cyclophosphamide may have grade 2C evidence for use in MPGN, those trials were done in an era preceding the novel classification (41). Nevertheless, treatment of rapidly progressive crescentic variant of the disease would favor using of cytotoxic agents earlier than later.…”

Response of type I membranoproliferative glomerulonephritis to pulse methylprednisolone and alternate-day prednisone therapy

“…Approximately 50% of untreated patients will progress to end-stage renal failure within 10 years of onset [2][3][4]. Although several forms of therapy utilizing combinations of corticosteroids, antiplatelet agents, immunosuppressive drugs, and anticoagulants have been reported [5][6][7][8][9][10][11][12][13], the best form of therapy remains to be determined. In this report, we describe the results of treatment with "pulse" methylprednisolone followed by alternate-day prednisone in 16 children with type I MPGN.…”