Treatment of idiopathic FSGS with adrenocorticotropic hormone gel

Abstract

Background and objectives: Adrenocorticotropic hormone (ACTH) has shown efficacy as primary and secondary therapy for nephrotic syndrome due to membranous nephropathy. The data on using ACTH to treat idiopathic FSGS are limited. This report describes our experience using ACTH for nephrotic syndrome due to idiopathic FSGS in the United States.

Design, setting, participants, & measurements: Twenty-four patients with nephrotic syndrome from idiopathic FSGS were treated with ACTH gel at two academic medical centers between 2009 and 2012, either as part of investigator-initiated pilot studies (n=16) or by prescription for treatment-resistant FSGS (n=8). The primary outcome was remission of proteinuria. The median dose of ACTH was 80 units injected subcutaneously twice weekly. Treatment durations were not uniform.

Results: Twenty-two patients had received immunosuppression (mean, 2.2 medications) before ACTH therapy. Six patients had steroid-dependent and 15 had steroid-resistant FSGS. At the time of ACTH initiation, the median serum creatinine (interquartile range) was 2.0 (1.1-2.7) mg/dl, estimated GFR was 36 (28-78) ml/min per 1.73 m(2), and urine protein-to-creatinine ratio was 4595 (2200-8020) mg/g. At the end of ACTH therapy, 7 of 24 patients (29%) experienced remission (n=2 complete remissions, n=5 partial remissions). All remitters had steroid-resistant (n=5) or steroid-dependent (n=2) FSGS. Two responders relapsed during the follow-up period (mean ± SD, 70±31 weeks). Adverse events occurred in 21 of 24 patients, including one episode of new-onset diabetes that resolved after stopping ACTH and two episodes of AKI.

Conclusions: Response to ACTH treatment among steroid-resistant or steroid-dependent patients with FSGS is low, but ACTH gel may be a viable treatment option for some patients with resistant nephrotic syndrome due to idiopathic FSGS. Further research is necessary to determine which patients will respond to therapy.

Trial registration: ClinicalTrials.gov NCT01129284 NCT01155141.

Figures

Figure 1.

Proteinuria trend versus time for seven patients who achieved remission with adrenocorticotropic hormone (ACTH). Time zero demarcates the end of the ACTH treatment course for each patient. Patients 15 and 23 experienced relapse after ACTH therapy, with patient 15 not meeting remission criteria because of worsened renal function, and patient 23 attaining remission in proteinuria with a repeat course of Stanford Protocol ACTH but not meeting criteria for remission based on serum creatinine. Additional immunosuppressive therapy used during follow-up period: patient 3, mycophenolate mofetil and tacrolimus; patient 12, mycophenolate mofetil; patient 23, cyclosporine and ACTH.