Intravenous Pulse cyclophosphamide and steroids induce immunological and clinical remission in New-incident and relapsing Primary Membranous Nephropathy

AIM: Primary membranous nephropathy (PMN) is associated with progression to end stage renal disease in some patients. Standard immunosuppressive therapy with cyclical cyclophosphamide and corticosteroids can be associated with significant adverse effects. We aimed to assess immunological and clinical response with intravenous pulse cyclophosphamide and oral steroids in patients with severe nephrotic syndrome - in a prospective observational cohort study at our centre.

METHODS: 17 consecutive patients (9 New-incident and 8 relapses) with severe nephrotic syndrome received intravenous pulse cyclophosphamide and daily oral steroids after failure to achieve remission with supportive therapy alone. Immunosuppressive therapy was discontinued at 6 months or earlier if proteinuria regressed to <100mg/mmol and patients were followed for at least 12 months. Achievement of partial remission was primary outcome; changes in proteinuria, eGFR, serum albumin and anti-phospholipase A2 receptor antibodies were secondary outcomes.

RESULTS: Dose of cyclophosphamide received was 5.4gm in New-incident patients and 4.2gm in patients with relapses. All 17 patients achieved partial remission within 6 months: proteinuria improved from 656 to 102mg/mmol at 6-months and 55mg/mmol at 12-months (p < 0.001); eGFR improved from 31 to 48ml/min/1.73m(2) at 6-months and 45ml/min/1.73m(2) at 12-months (p < 0.05). Anti-PLA2 R levels reduced from 244 to 10U/L at 6-months and 10U/L at 12-months (p < 0.001). 2 out of the 9 patients in the New-incident group developed subsequent relapse. Cumulative dose of cyclophosphamide and steroids received was about half of conventional regime.

CONCLUSION: Monthly intravenous pulse cyclophosphamide with oral steroids induced immunological and clinical partial remission at significantly reduced cyclophosphamide and steroid doses in PMN.