title: Synthetic ACTH in High Risk Patients with Idiopathic Membranous Nephropathy: A Prospective, Open Label Cohort Study.
abstract: New therapeutic agents are warranted in idiopathic membranous nephropathy. Synthetic ACTH may be advantageous with reported remission rates up to 85% and few side effects. We conducted a prospective open label cohort study from 2008 till 2010 (NCT00694863). We prospectively selected patients with idiopathic membranous nephropathy and high risk for progression (defined as βeta-2-microglobulin (β2m) excretion of >500 ng/min). For comparison, we selected matched historical controls treated with cyclophosphamide. The prospectively selected patients received intramuscular injections of synthetic ACTH during 9 months (maximal dose 1 mg twice a week). The primary endpoints concerned the feasibility and incidence of remissions as a primary event. Secondary endpoints included side effects of treatment and the incidence of remissions and relapses at long-term follow-up. Twenty patients (15 men) were included (age 54±14 years, serum creatinine 104 μmol/l [IQR 90–113], urine protein:creatinine ratio 8.7 g/10 mmol creatinine [IQR 4.3–11.1]). Seventeen patients (85%) completed treatment. 97% of injections were administered correctly. Cumulative remission rate was 55% (complete remission in 4 patients, partial remission 7 patients). In a group of historical controls treated with cyclophosphamide and steroids, 19 of 20 patients (95%) developed a remission (complete remission in 13 patients, partial remission in 6 patients) (p<0.01). The main limitation of our study is its small size and the use of a historical control group. We show that treatment with intramuscular injections of synthetic ACTH is feasible. Our data suggest that synthetic ACTH is less effective than cyclophosphamide in inducing a remission in high risk patients with idiopathic membranous nephropathy. The use of synthetic ACTH was also associated with many adverse events. Therefore, we advise against synthetic ACTH as standard treatment in membranous nephropathy.
authors.affiliation: Radboud university medical center, Radboud Institute for Health Sciences, Department of Nephrology, Nijmegen, The Netherlands.
authors.forename: Anne-Els
authors.initials: AE
authors.lastname: van de Logt
authors.affiliation: Maxima medical center, Department of Internal Medicine, Veldhoven, The Netherlands.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Beerenhout
authors.affiliation: Medisch Spectrum Twente, Department of Internal Medicine, Enschede, The Netherlands.
authors.forename: Hans S
authors.initials: HS
authors.lastname: Brink
authors.affiliation: Bernhoven Hospital, Department of Internal Medicine, Uden, The Netherlands.
authors.forename: Jos J
authors.initials: JJ
authors.lastname: van de Kerkhof
authors.affiliation: Radboud university medical center, Radboud Institute for Health Sciences, Department of Nephrology, Nijmegen, The Netherlands.
authors.forename: Jack F
authors.initials: JF
authors.lastname: Wetzels
authors.affiliation: Radboud university medical center, Radboud Institute for Health Sciences, Department of Nephrology, Nijmegen, The Netherlands.
authors.forename: Julia M
authors.initials: JM
authors.lastname: Hofstra
mesh_terms: D000328:Adult; D003366:Cosyntropin / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D012893:Sleep Wake Disorders / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D003366:Cosyntropin; D003520:Cyclophosphamide