Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH) gel

Abstract

Purpose:A synthetic adrenocorticotropin (ACTH) analog has shown efficacy in Europe as primary and secondary therapy for nephrotic syndrome, but there is no published experience using the natural, highly purified ACTH gel formulation, available in the United States, for nephrotic syndrome. We therefore investigated the use of ACTH gel for nephrotic syndrome in the United States.Patients and methods:Twenty-one patients with nephrotic syndrome treated with ACTH gel outside of research settings in the United States, with initiation of therapy by December 31, 2009, allowing a minimum 6 months follow-up. We defined complete remission as stable renal function with proteinuria falling to <500 mg/day, and partial remission as stable renal function with >50% reduction in proteinuria from 500 to 3500 mg/day.Results:Twenty-one patients with nephrotic syndrome were treated: 11 with idiopathic membranous nephropathy (iMN), 4 with membranoproliferative glomerulonephritis (MPGN), 1 with focal segmental glomerulosclerosis (FSGS), 1 with minimal change disease (MCD), 1 with immunoglobulin A (IgA) nephropathy, 1 with class V systemic lupus erythematosus (SLE) glomerulonephritis, 1 with monoclonal diffuse proliferative glomerulonephritis, and 1 with unbiopsied nephrotic syndrome. ACTH was used as primary therapy for 3 patients; the remaining patients had previously failed a mean 2.3 immunosuppressive regimens. Eleven patients achieved a complete or partial remission, with 4 (19%) in complete remission. Of the 11 patients who achieved remission, 9 had iMN, 1 had FSGS, and 1 had IgA nephropathy. Of the 11 patients with iMN, 3 (27%) achieved complete remission and 6 (55%) achieved partial remission despite having previously failed a mean 2.4 therapies. Five patients reported steroid-like adverse effects, but there were no severe infections. The limitations were retrospective data analysis with short-term follow-up.Conclusion:ACTH gel may be a viable treatment option for resistant nephrotic syndrome due to membranous nephropathy. Short-term data suggest that remission rates may approach 80%.

The Treatment of Minimal Change Disease in Adults

“…41 Other Immunomodulatory Treatments for FR, SD, or Steroid-Responsive Disease The use of levimasole, which has been used in children with MCD, has not been reported in adults. Adrenocorticotropin hormone (ACTH) gel use was reported without success in one patient who had previously failed or relapsed after steroid, MMF, and calcineurin inhibitor therapy, 84 and ACTH led to partial remission in one of two resistant MCD patients in another case series; this patient relapsed 4 weeks after discontinuing ACTH therapy. 85 A pilot study recently showed that adding the protease inhibitor saqauinavir to immunosuppression regimens in adults and children with SR and SD MCD may decrease proteinuria and steroid requirements in these patients.…”

Balancing Cancer Risk and Efficacy of Using Cyclophosphamide to Treat Idiopathic Membranous Nephropathy

“…Optimal dosing regimen, retreatment schedule, and long term effects, however, are yet to be corroborated by large trials. Finally, synthetic ACTH has been shown to be effective in reducing proteinuria (28)(29)(30) and similar results are evident with use of ACTH gel in the United States; however studies are small, and long term outcomes have not been determined (31).…”

Treatment of Acute Relapses in Multiple Sclerosis

“…However, more recent data in other disease states like nephrotic syndrome [37], opsoclonus-myoclonus [38], and infantile spasms [39] provide clinical evidence that steroidogenic actions fail to explain the efficacy of ACTH in these conditions. For example, in infantile spasms (a disease confined to the CNS), ACTH has been shown to alter brain function after systemic administration; this alteration cannot be explained by glucocorticoid actions because corticosteroid treatment has doubtful efficacy in infantile spasms and doses of ACTH that surpass those required to elicit maximal glucocorticoid release are required to obtain optimal efficacy [39].…”