Individualized therapy in patients with primary membranous nephropathy

In 70 % of patients anti-PLA2R antibodies (aPLA2R) can be identified. Although spontaneous remissions do occur, up to 50 % of patients may need immunosuppressive therapy. The KDIGO guideline recommend initial therapy with a 6-month course of alternating monthly cycles of an alkylating agent and steroids. In the literature different treatment protocols with variable duration of drug therapy are used, however in all studies treatment was not personalized. In previous studies it was shown that disappearance of aPLA2R preceded clinical remission by 2-3 months. We observed that in the majority of patients treated with cyclophosphamide (CP) and mycofenolic acid (MMF) aPLA2R disappeared after 2 months. Since august 2013 we use aPLA2R response to determine treatment duration in the individual patient. We use an antibody guided therapy protocol in patients treated with CP, MMF and tacrolimus. We expect that we will shorten the duration of therapy in many patients.

In 70 % of patients anti-PLA2R antibodies (aPLA2R) can be identified. Although spontaneous remissions do occur, up to 50 % of patients may need immunosuppressive therapy. The KDIGO guideline recommend initial therapy with a 6-month course of alternating monthly cycles of an alkylating agent and steroids. In the literature different treatment protocols with variable duration of drug therapy are used, however in all studies treatment was not personalized. In previous studies it was shown that disappearance of aPLA2R preceded clinical remission by 2-3 months. We observed that in the majority of patients treated with cyclophosphamide (CP) and mycofenolic acid (MMF) aPLA2R disappeared after 2 months. We use an antibody guided therapy protocol in patients treated with CP, MMF and tacrolimus. We expect that this will shorten the duration of therapy in many patients.

24 months

Since august 2013 we use aPLA2R response to determine treatment duration in the individual patient. In the case of treatment with CP and MMF (both in combination with steroids), aPLA2R are measured after resp. 8, 16 and 24 weeks with a commercial IFT. If antibodies are negative the CP/MMF is stopped and the steroids are tapered. If the aPLA2R antibodies are still positive after 24 weeks of treatment and no complete remission is achieved further treatment with another agent is recommended. A maximum treatment duration of 6 months after the achievement of a partial remission is prescribed.


In case of tacrolimus (also in combination with prednisone); aPLA2R are measured after 24 weeks. If antibodies are negative the tacrolimus and the steroids are tapered. If the aPLA2R are still positive after 24 weeks of treatment further treatment is recommended and aPLA2R are measured again after 48 weeks. If, after 48 weeks of treatment continuation of treatment is recommended and aPLA2R are measured again after 48 weeks. If, after 48 weeks of treatment aPLA2R are still positive and no complete remission is achieved, further treatment with Rituximab (1000 mg) is recommended and the tacrolimus and the steroids are tapered.


For the cyclophamide group a comparison with a historical control group (treated with cyclophosphamide and steroids for 6-12 months) will be made.