Low-dose synthetic adrenocorticotropic hormone-analog therapy for nephrotic patients: results from a single-center pilot study

Abstract

IntroductionThis report describes our experience using a low-dose synthetic adrenocorticotropic hormone (ACTH) analog for patients affected by nephrotic syndrome who had not responded to or had relapsed after steroid and immunosuppressive treatments.Patients and methodsEighteen adult nephrotic patients with an estimated glomerular filtration rate >30 mL/min were recruited. Histological pictures included ten of membranous nephropathy, three of membranous proliferative glomerulonephritis, three of minimal change, and two of focal segmental glomerular sclerosis. All patients received the synthetic ACTH analog tetracosactide 1 mg intramuscularly once a week for 12 months. Estimated glomerular filtration rate, proteinuria, serum lipids, albumin, glucose, and potassium were determined before and during the treatment.ResultsOne of the 18 patients discontinued the treatment after 1 month because of severe fluid retention, and two patients were lost at follow-up. Complete remission occurred in six cases, while partial remission occurred in four cases (55.5% responder rate). With respect to baseline, after 12 months proteinuria had decreased from 7.24±0.92 to 2.03±0.65 g/day (P<0.0001), and serum albumin had increased from 2.89±0.14 to 3.66±0.18 g/dL (P<0.0001). Total and low-density lipoprotein cholesterol had decreased from 255±17 to 193±10 mg/dL (P=0.01), and from 168±18 to 114±7 mg/dL (P=0.03), respectively. No cases of severe worsening of renal function, hyperglycemia, or hypokalemia were observed, and no admissions for cardiovascular or infectious events were recorded.ConclusionTetracosactide administration at the dosage of 1 mg intramuscularly per week for 12 months seems to be an acceptable alternative for nephrotic patients unresponsive or relapsing after steroid-immunosuppressive regimens. Further studies should be planned to assess the effect of this low-dose ACTH regimen also in nephrotic patients not eligible for kidney biopsy or immunosuppressive protocols.

Efficacy and safety of adrenocorticotropic hormone treatment in glomerular diseases: a systematic review and meta-analysis

“…Three hundred and one articles were excluded after the initial screening and 42 articles were included for full-length review. Eventually, 19 articles met all the inclusion criteria [ 3 – 7 , 11 – 13 , 19 – 29 ]. Details of these studies are outlined in Table 1 .…”

“…It fell out of favor after easy-to-use synthetic oral glucocorticoids became available [ 2 ]. Recently, ACTH has been resurrected as a potential therapeutic option for a variety of glomerular diseases [ 3 – 7 ]. In addition to its steroidogenesis effects, ACTH acts as an agonist of the melanocortin system, which plays a role in various physiologic functions, including melanin synthesis, immunomodulation, anti-inflammation, lipolysis stimulation and modulation of exocrine function [ 8 ].…”

“…Since the therapeutic effect of ACTH on nephrotic syndrome was first reexamined by Berg et al . [ 3 ] in 1999, the literature on its use in various glomerular diseases has rapidly expanded [ 4 – 7 , 11 – 13 ]. However, the exact efficacy of ACTH in inducing remission in patients with glomerular diseases and the frequency of adverse effects associated with the use of ACTH remain largely unknown.…”

Experience With Acth In Membranous Nephropathy In Older Patients

“…The ACTH dose used in these studies was similar to ours with few side effects necessitating cessation of therapy. Lorusso [10] et al could not attain a similar remission in refractory patients in a study with weekly injections of low dose ACTH (tetracosactid) continued for one year. The mean age of the 6 patients we evaluated is quite higher than of other series.…”

Development and Study of Semi-Solid Preparations Containing the Model Substance Corticotropin (ACTH): Convenience Application in Neurodegenerative Diseases

“…Three preparations containing ACTH are registered and used: H.P. Acthar ® Gel, Cortrosyn TM, and Synacthen ® Depot [21,22]. All these preparations are injected.…”