SUN-035 A MODIFIED – ‘MODIFIED PONTICELLI’ REGIMEN - FOR IDIOPATHIC MEMBRANOUS NEPHROPATHY

Abstract

Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults worldwide. Treatment using cyclical cyclophosphamide and steroids (‘modified Ponticelli’ regimen) has been the standard of care for decades, however potential therapy-related adverse effects are a significant concern. At our center, we have used lower-than-standard dose intravenous pulse steroid based modification of the conventional ‘modified Ponticelli’ regimen to minimize steroid-related adverse effects (Figure 1). The aim of this study was to assess the efficacy and safety of this regimen in IMN. This was a case-record based retrospective analysis conducted at our center over a period of nine years (January 2008-December 2017). All treatment-naive patients with primary MN fulfilling the following criteria: (1) biopsy proven MN and (2) initiated with a lower-than-standard dose pulse steroid-based modification of the conventional ‘modified Ponticelli’ regimen (Figure 1) were included. Clinical and laboratory parameters of all patients were recorded. Remission rates (both complete and partial) and adverse effects of therapy at the end of 6 months of therapy were studied. Follow-up data up was also collected. The study definitions used are as follows: Complete remission: Proteinuria < 0.3g/day or UPCR <0.3 mg/mg, with normalization of serum albumin (≥3.5g/dL) Partial remission: Reduction of 24 hour urine protein (or UPCR) to < 50% of baseline to < 3.5g/day (or UPCR <3.5mg/mg), but > 0.3g/day (or UPCR > 0.3mg/mg) Relapse: Proteinuria >3.5g/day or >3500mg/g urine creatinine after remission has been attained. Analysis was carried out using SPSS version 18. A total of 41 patients were included. Baseline characteristics are shown in Table 1. All patients received either angiotensin converting enzyme inhibitors/ angiotensin receptor blockers (ACEi/ARBS) as supportive therapy. Immunosuppression was stopped prior to completion of six months for four patients due to infection, while six patients were lost to follow-up. Of the 31 patients who completed six months of therapy, 71% (n=22) responded to therapy [complete remission in 25.8% (n=8), partial remission in 45.2% (n=14)] and 29% (n=9) failed to respond (Table 2). Most common complications seen during therapy were infections in 25.7% (n=9/35, of which immunosuppression was discontinued for four patients), steroid induced diabetes mellitus in 40% (n=14/35), and leucopenia in 8.5% (n=3/35).[R[1] The relapse rate during follow-up (mean follow-up period: 35.6 months) was 29% (n=9). Anti-PLA2R titers and percentage of glomerulosclerosis at presentation were significantly associated with response at 6 months (p<0.05).View Large Image Figure ViewerDownload Hi-res image Download (PPT)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Use of lower-than-standard dose pulse steroid and cyclophosphamide is effective in achieving remission in idiopathic membranous nephropathy. Further large randomized control trials with longer follow-up are needed to confirm the same.