Melanocortin 1 Receptor Agonists Reduce Proteinuria

Lindskog, Annika; Ebefors, Kerstin; Johansson, Martin; Stefánsson, Bergur V.; Granqvist, Anna; Arnadottir, Margret; Berg, Anna‐Lena; Nyström, Jenny; Haraldsson, Börje

doi:10.1681/asn.2009101025

Cited by 98 publications

(145 citation statements)

References 34 publications

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“…Similar results have been obtained with natural ACTH (Acthar gel) in a small observational study (44). The mechanism of action of ACTH may be related to the stimulation of melanocortin receptors with inhibition of immune and inflammatory response or a direct action on podocyte stability (45). ACTH can be a reasonable option for patients who have contraindications to or who do not respond to cyclical alkylating agent-steroid therapy or calcineurin inhibitors.…”

Section: What Treatment Regimens Are Effective and Safe For Patients supporting

confidence: 73%

Glomerular Diseases

Ponticelli

Glassock

2014

Clinical Journal of the American Society of Nephrology

173

127

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SummaryMembranous nephropathy (MN) is an autoimmune disease usually associated with a nephrotic syndrome and it may progress to ESRD in the long term. Its etiology is often unknown (idiopathic MN), whereas other cases have a recognizable etiology (secondary MN). In idiopathic MN, the glomerular lesions are mainly caused by autoantibodies against a podocyte membrane protein, the M-type of phospholipase A2 receptor 1. The natural course of idiopathic MN is quite varied with spontaneous complete or partial remissions a relatively common occurrence. Patients with asymptomatic non-nephrotic proteinuria seldom progress and need only conservative management. Those with persistent full-blown nephrotic syndrome and those with declining renal function are candidates for specific treatment with any of several regimens. Cyclical therapy with alternating monthly intravenous and oral glucocorticoids combined with a cytotoxic agent can induce remission and preserve renal function in the long term. Cyclosporine or tacrolimus can induce remission, but relapses are frequent after the drug withdrawal. Mycophenolate mofetil monotherapy seems to be ineffective, but may be beneficial when administered together with steroids. The experience with adrenocorticotropic hormone, natural or synthetic, is limited to a few studies with short-term follow-up, but high rates of remission can be seen after prolonged treatment. A high rate of remission and good tolerance have also been reported with rituximab. Patients with moderate renal insufficiency may also benefit from treatment, but at a price of frequent and serious side effects. With these limitations in mind, idiopathic MN may be considered a treatable disease in many patients.

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Section: What Treatment Regimens Are Effective and Safe For Patients supporting

confidence: 73%

Glomerular Diseases

Ponticelli

Glassock

2014

Clinical Journal of the American Society of Nephrology

173

127

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“…30 Recurrent disease presents earlier than de novo MN, typically within two years (15 months vs 4 years for de novo). As yet, there seem to be no markers 1 g methylprednisolone daily for three days followed by oral methylprednisolone 0.5 mg/kg/day for the rest of the first month.…”

Section: Recurrent and De Novo Membranous Nephropathy In Renal Transpmentioning

confidence: 99%

Membranous nephropathy

Mathieson

2012

Clinical Medicine

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“…There has been recent interest in the role of ACTH in treating the nephrotic syndrome and in the noncorticosteroid actions of this drug (26). A synthetic ACTH analogue (tetracosactide, Synacthen R, Novartis Pharmaceuticals, Basel, Switzerland) and a highly purified ACTH gel (H.P.…”

Section: Introductionmentioning

confidence: 99%

“…A synthetic ACTH analogue (tetracosactide, Synacthen R, Novartis Pharmaceuticals, Basel, Switzerland) and a highly purified ACTH gel (H.P. Acthar Gel, Questcor Pharmaceuticals, Inc., Union City, CA) have been used for patients with nephrotic syndrome (26)(27)(28)(29)(30)(31)(32), predominantly in those with membranous nephropathy. To date, the literature describes only five patients (one patient in Europe and four patients in the United States) with nephrotic syndrome due to idiopathic FSGS who have been treated with ACTH; one patient achieved complete response and two patients achieved partial response (27,30,32).…”

Section: Introductionmentioning

confidence: 99%

Treatment of Idiopathic FSGS with Adrenocorticotropic Hormone Gel

Hogan

Bomback

Mehta

et al. 2013

Clinical Journal of the American Society of Nephrology

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SummaryBackground 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 6 SD, 70631 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.

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Melanocortin 1 Receptor Agonists Reduce Proteinuria

Cited by 98 publications

References 34 publications

Glomerular Diseases

Glomerular Diseases

Membranous nephropathy

Treatment of Idiopathic FSGS with Adrenocorticotropic Hormone Gel

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