Intravenous cyclophosphamide and oral prednisolone is a safe and effective treatment option for idiopathic membranous nephropathy

Abstract

Background: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults. A proportion of patients will experience spontaneous remission and the decision to offer immunosuppression is guided by the presence of adverse prognostic features. Data relating to the efficacy of different immunosuppressive protocols is lacking, in particular there are little data available on the efficacy or benefits of an intravenous (IV) cyclophosphamide-based regimen. Since 2010, our unit has been using a treatment regimen based on IV cyclophosphamide and oral prednisolone for patients with IMN associated with adverse prognostic features. The outcomes of these patients were compared with a historic cohort of similar patients who did not receive immunosuppressive therapy.

Methods: Between January 2010 and 2014, a total of 41 patients were treated with pulse IV cyclophosphamide and oral prednisolone. The historical comparator group included 47 similar patients diagnosed between 2006 and 2010 who did not receive immunosuppression. Two-year follow-up data were collected. The primary outcome measure was time to remission of nephrotic syndrome (defined as normalization of serum albumin). Secondary outcomes included rate of progression of kidney disease as well as incidence of treatment-related adverse events.

Results: As compared with supportive care alone, treatment with IV cyclophosphamide and oral prednisolone was associated with a significantly higher number of patients achieving remission. Within 18 months of therapy, 74% of treated patients had achieved a normal serum albumin level. Though there was a trend towards a more rapid decline in estimated glomerular filtration rate in the untreated cohort, this did not reach statistical significance. The IV cyclophosphamide-based regimen was well tolerated, with few significant treatment-associated side effects.

Conclusion: IV cyclophosphamide is a safe and effective treatment for IMN.

Keywords: albumin; glomerulonephritis; immunosuppression; membranous nephropathy; nephrotic syndrome.

Fig. 1

Kaplan–Meier curve showing time to normalization of serum albumin (albumin  ≥35 g/L) in treated and untreated patients.

Fig. 2

Kaplan–Meier curve showing time to a further 30% decrease in eGFR from the time of biopsy in treated and untreated patients.

Fig. 3

Change in albumin (g/L) from baseline (mean ± standard error) post-treatment.

Fig. 4

Percentage of patients with normal serum albumin (>35 g/L) post-treatment.