Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial.

Abstract

BACKGROUND:

Adrenocorticotropic hormone (ACTH) has shown promising results in glomerular diseases resistant to conventional therapies, but the reported data have solely been from retrospective, observational studies.

METHODS:

In this prospective, open-label study (NCT01129284), 15 subjects with resistant glomerular diseases were treated with ACTH gel (80 units subcutaneously twice weekly) for 6 months. Resistant membranous nephropathy (MN), minimal change disease (MCD), and focal segmental glomerulosclerosis (FSGS) were defined as failure to achieve sustained remission of proteinuria off immunosuppressive therapy with at least 2 treatment regimens; resistant IgA nephropathy was defined as >1 g/g urine protein:creatinine ratio despite maximally tolerated RAAS blockade. Remission was defined as stable or improved renal function with ≥50% reduction in proteinuria to <0.5 g/g (complete remission) or 0.5-3.5 g/g (partial remission).

RESULTS:

The study included 5 subjects with resistant idiopathic MN, 5 subjects with resistant MCD (n = 2)/FSGS (n = 3), and 5 subjects with resistant IgA nephropathy. Two resistant MN subjects achieved partial remission on ACTH therapy, although 3 achieved immunologic remission of disease (PLA(2)R antibody disappeared by 4 months of therapy). One subject with resistant FSGS achieved complete remission on ACTH; one subject with resistant MCD achieved partial remission but relapsed within 4 weeks of stopping ACTH. Two subjects with resistant IgA nephropathy demonstrated >50% reductions in proteinuria while on ACTH, with proteinuria consistently <1 g/g by 6 months. Three of 15 subjects reported significant steroid-like adverse effects with ACTH, including weight gain and hyperglycemia, prompting early termination of therapy without any clinical response.

CONCLUSIONS:

ACTH gel is a promising treatment for resistant glomerular diseases and should be studied further in controlled trials against currently available therapies for resistant disease.

• Authors: Andrew S Bomback, Pietro A Canetta, Laurence H Beck Jr, Rivka Ayalon, Jai Radhakrishnan, Gerald B Appel
• Journal: American journal of nephrology (Am J Nephrol) Vol. 36 Issue 1 Pg. 58-67 ( 2012) ISSN: 1421-9670 [Electronic] Switzerland
• PMID: 22722778 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 S. Karger AG, Basel.

Chemical References

• Gels
• Adrenocorticotropic Hormone

Topics

• Adrenocorticotropic Hormone (therapeutic use)
• Adult
• Aged
• Female
• Gels (therapeutic use)
• Glomerulonephritis, Membranous (drug therapy)
• Glomerulosclerosis, Focal Segmental (drug therapy)
• Humans
• Kidney Glomerulus (drug effects)
• Male
• Middle Aged
• Nephrosis, Lipoid (drug therapy)
• Nephrotic Syndrome (drug therapy)
• Prospective Studies
• Proteinuria (therapy)
• Remission Induction
• Treatment Outcome