Treatment of idiopathic FSGS with adrenocorticotropic hormone gel

Clin J Am Soc Nephrol. 2013 Dec;8(12):2072-81. doi: 10.2215/CJN.02840313. Epub 2013 Sep 5.

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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Academic Medical Centers
  • Adrenocorticotropic Hormone / administration & dosage*
  • Adrenocorticotropic Hormone / adverse effects
  • Adult
  • California
  • Drug Administration Schedule
  • Female
  • Gels
  • Glomerulosclerosis, Focal Segmental / complications
  • Glomerulosclerosis, Focal Segmental / diagnosis
  • Glomerulosclerosis, Focal Segmental / drug therapy*
  • Humans
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Nephrotic Syndrome / congenital
  • Nephrotic Syndrome / diagnosis
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / etiology
  • New York City
  • Prospective Studies
  • Recurrence
  • Remission Induction
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Gels
  • Adrenocorticotropic Hormone

Supplementary concepts

  • Nephrotic syndrome, idiopathic, steroid-resistant

Associated data

  • ClinicalTrials.gov/NCT01129284
  • ClinicalTrials.gov/NCT01155141