Background To assess whether stable renal function can be maintained with immunosuppressive therapy in patients with idiopathic membranous nephropathy who are experiencing declining renal function. Methods This randomised controlled trial was conducted in 37 renal units across the UK. Patients (aged 18-75 years) with biopsy-proven idiopathic membranous nephropathy had plasma creatinine concentrations of less than 300 μmol/L and had at least a 20% reduction in glomerular filtration rate over the 2 years prior to enrolment, based on at least three measurements over a period of at least 3 months. Patients were randomly assigned (1:1:1) to receive either supportive therapy alone, supportive therapy plus 6 months of alternating cycles of prednisolone and nitrogen mustard phenylbutyrate, or supportive therapy plus 12 months of cyclosporine, using a randomized number table. The primary evaluation was a further 20% reduction in renal function relative to baseline. The study was registered as an International Standard Randomised Controlled Trial (ISRCT), registration number 99959692. Results 108 patients were randomised, of whom 33 were treated with prednisolone and phenylbutyrate, 37 with cyclosporine and 38 with received supportive care. Forty-five patients deviated from the intended regimen by the end of the study, most of them due to small dose adjustments. Patients who did not meet the primary endpoint were followed up to the primary endpoint or at least 3 years. The risk of a further 20% decline in renal function was significantly lower in the prednisolone and phenylbutyrate group than in the supportive care group (19/33 patients [58%] met the endpoint vs 31/37 [84%]; there was no difference between the risk in the cyclosporine group (29/36 [81%]) and the supportive care group alone. Serious adverse events were more frequent in all three groups, but were higher in the prednisolone and benztropine group than in the supportive care alone group (56 events vs 24 events; p=0,048). Interpretation of results In the subgroup of patients with idiopathic membranous nephropathy and deteriorating renal excretion, our evidence best supports a 6-month treatment regimen with prednisolone and phenylbutyrate. Cyclosporine should be avoided in this patient subgroup. However, be aware of serious adverse events associated with prednisolone and phenylbutyrate mustard.