Research Article: Immunosuppressive regimens based on Cyclophospamide or Calcineurin inhibitors: Comparison of their effect in the long term outcome of Primary Membranous Nephropathy

Date Published: August 12, 2019

Publisher: Public Library of Science

Author(s): Maria Stangou, Smaragdi Marinaki, Evangelos Papachristou, Kyriaki Kolovou, Erasmia Sambani, Synodi Zerbala, Panagiota Papadea, Olga Balafa, Karolos-Pavlos Rapsomanikis, Aimilios Andrikos, Panagiota Manolakaki, Dorothea Papadopoulou, Efstathios Mitsopoulos, Helen Liakou, Paraskevi-Evi Andronikidi, Vasiliki Choulitoudi, George Moustakas, Dimitra Galitsiou, Eugene Dafnis, Kostas Stylianou, Ioannis Stefanidis, Spyridon Golfinopoulos, Stylianos Panagoutsos, Maria Tsilivigkou, Apostolos Papadogianakis, Ioannis Tzanakis, Athanasios Sioulis, Dimitrios Vlachakos, Eirini Grapsa, Sophia Spaia, Nikolaos Kaperonis, Christos Paliouras, Christos Dioudis, Fani Papoulidou, Theofanis Apostolou, Christos Iatrou, Ioannis Boletis, Dimitrios Goumenos, Aikaperini Papagianni, Vivekanand Jha.


Management of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up.

The aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN.

Clinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens.

Twenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14–87) yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n = 381) compared to those initially treated with Cyclo (n = 110), relapse rate: 25.2% vs. 6.4%, p<0.0001, and no response rate: 22.5% vs. 13.6%, p = 0.04, respectively. Long term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

Partial Text

Membranous Nephropathy (MN) is the most common cause of nephrotic syndrome in adults, with an overall global incidence reaching to 1.2 per 100,000 per year, as estimated in a recent review covering the period 1980–2010 [1,2]. Outcome of disease is variable, ranging from spontaneous remission to progressive renal failure reaching end stage renal disease [1–4]. Undoubtedly, after the discovery of innovative pathogenic antibodies, the M-type phospholipase A2 receptor (PLA2R), we are on the way to changing our aspect on the disease, in terms of research and clinical management [5–7]. However, critical questions regarding diagnostic approach and follow up, assessment of renal biopsy findings, and most importantly, selecting and applying the best therapeutic regime for each patient still remain.

To our knowledge, this study, based on a database of 752 PMN patients, has included the largest number of patients with the longest follow up, reaching more than 10years.




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