Treatment of resistant glomerular diseases with adrenocorticotropic hormone gel: a prospective trial.
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.
Division of Nephrology, Department of Medicine, Columbia University Medical Center, New York, NY, USA. asb68@columbia.edu
Andrew S
AS
Bomback
Pietro A
PA
Canetta
Laurence H
LH
Beck
Rivka
R
Ayalon
Jai
J
Radhakrishnan
Gerald B
GB
Appel
D000324:Adrenocorticotropic Hormone / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D005260:Female; D005782:Gels / Q000627:therapeutic use*; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy*; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000188:drug therapy*; D009404:Nephrotic Syndrome / Q000188:drug therapy; D011446:Prospective Studies; D011507:Proteinuria / Q000628:therapy; D012074:Remission Induction; D016896:Treatment Outcome
D005782:Gels; D000324:Adrenocorticotropic Hormone