A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar® Gel) in nephrotic syndrome due to idiopathic membranous nephropathy

Michelle A. Hladunewich, Daniel Cattran, Laurence H. Beck, Ayodele Odutayo, Sanjeev M Sethi, Rivka Ayalon, Nelson Leung, Heather Reich, Fernando Custodio Fervenza

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

BackgroundH.P. Acthar® Gel is currently the only Food and Drug Administration therapy approved for the treatment of nephrotic syndrome. Active drug ingredients include structurally related melanocortin peptides that bind to cell surface G-protein-coupled receptors known as melanocortin receptors, which are expressed in glomerular podocytes. In animal models of membranous nephropathy, stimulation has been demonstrated to reduce podocyte injury and loss. We hypothesized that H.P. Acthar® Gel would improve symptoms of the nephrotic syndrome in patients with idiopathic membranous nephropathy. MethodsTwenty patients received a subcutaneous dose of 40 or 80 IU twice weekly. Changes in proteinuria, albumin, cholesterol profile, estimated glomerular filtration rate and serum anti-PLA2R antibodies were assessed at baseline and in response to treatment along with tolerance and safety. ResultsBaseline characteristics included mean proteinuria (9.1 ± 3.4 g/day), albumin (2.7 ± 0.8 g/dL), estimated glomerular filtration rate (77 ± 30 mL/min) along with elevated total and low-density lipoprotein (LDL) cholesterol. By 12 months of follow-up, there was a significant improvement in proteinuria in the entire cohort, decreasing to 3.87 ± 4.24 g/day (P < 0.001) with significant improvements in serum albumin, total and LDL cholesterol. A >50% decrease in proteinuria was noted in 65% of the patients with a trend toward better outcomes among patients who received greater cumulative doses. No significant adverse effects were documented. Clearing of serum anti-PLA2R antibodies prior to or in parallel with proteinuria improvement was noted in some, but not all patients. ConclusionsH.P. Acthar® Gel is a potential therapy for nephrotic syndrome secondary to idiopathic membranous nephropathy that deserves further study.

Original languageEnglish (US)
Pages (from-to)1570-1577
Number of pages8
JournalNephrology Dialysis Transplantation
Volume29
Issue number8
DOIs
StatePublished - 2014

Fingerprint

Membranous Glomerulonephritis
Nephrotic Syndrome
Proteinuria
Adrenocorticotropic Hormone
Gels
Podocytes
Glomerular Filtration Rate
Anti-Idiotypic Antibodies
Albumins
Melanocortin Receptors
Melanocortins
United States Food and Drug Administration
G-Protein-Coupled Receptors
Serum
LDL Cholesterol
Membrane Proteins
Therapeutics
Animal Models
Cholesterol
Safety

Keywords

  • ACTH (H.P. Acthar® Gel)
  • membranous nephropathy
  • nephrotic syndrome

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar® Gel) in nephrotic syndrome due to idiopathic membranous nephropathy. / Hladunewich, Michelle A.; Cattran, Daniel; Beck, Laurence H.; Odutayo, Ayodele; Sethi, Sanjeev M; Ayalon, Rivka; Leung, Nelson; Reich, Heather; Fervenza, Fernando Custodio.

In: Nephrology Dialysis Transplantation, Vol. 29, No. 8, 2014, p. 1570-1577.

Research output: Contribution to journalArticle

Hladunewich, Michelle A. ; Cattran, Daniel ; Beck, Laurence H. ; Odutayo, Ayodele ; Sethi, Sanjeev M ; Ayalon, Rivka ; Leung, Nelson ; Reich, Heather ; Fervenza, Fernando Custodio. / A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar® Gel) in nephrotic syndrome due to idiopathic membranous nephropathy. In: Nephrology Dialysis Transplantation. 2014 ; Vol. 29, No. 8. pp. 1570-1577.
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abstract = "BackgroundH.P. Acthar{\circledR} Gel is currently the only Food and Drug Administration therapy approved for the treatment of nephrotic syndrome. Active drug ingredients include structurally related melanocortin peptides that bind to cell surface G-protein-coupled receptors known as melanocortin receptors, which are expressed in glomerular podocytes. In animal models of membranous nephropathy, stimulation has been demonstrated to reduce podocyte injury and loss. We hypothesized that H.P. Acthar{\circledR} Gel would improve symptoms of the nephrotic syndrome in patients with idiopathic membranous nephropathy. MethodsTwenty patients received a subcutaneous dose of 40 or 80 IU twice weekly. Changes in proteinuria, albumin, cholesterol profile, estimated glomerular filtration rate and serum anti-PLA2R antibodies were assessed at baseline and in response to treatment along with tolerance and safety. ResultsBaseline characteristics included mean proteinuria (9.1 ± 3.4 g/day), albumin (2.7 ± 0.8 g/dL), estimated glomerular filtration rate (77 ± 30 mL/min) along with elevated total and low-density lipoprotein (LDL) cholesterol. By 12 months of follow-up, there was a significant improvement in proteinuria in the entire cohort, decreasing to 3.87 ± 4.24 g/day (P < 0.001) with significant improvements in serum albumin, total and LDL cholesterol. A >50{\%} decrease in proteinuria was noted in 65{\%} of the patients with a trend toward better outcomes among patients who received greater cumulative doses. No significant adverse effects were documented. Clearing of serum anti-PLA2R antibodies prior to or in parallel with proteinuria improvement was noted in some, but not all patients. ConclusionsH.P. Acthar{\circledR} Gel is a potential therapy for nephrotic syndrome secondary to idiopathic membranous nephropathy that deserves further study.",
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T1 - A pilot study to determine the dose and effectiveness of adrenocorticotrophic hormone (H.P. Acthar® Gel) in nephrotic syndrome due to idiopathic membranous nephropathy

AU - Hladunewich, Michelle A.

AU - Cattran, Daniel

AU - Beck, Laurence H.

AU - Odutayo, Ayodele

AU - Sethi, Sanjeev M

AU - Ayalon, Rivka

AU - Leung, Nelson

AU - Reich, Heather

AU - Fervenza, Fernando Custodio

PY - 2014

Y1 - 2014

N2 - BackgroundH.P. Acthar® Gel is currently the only Food and Drug Administration therapy approved for the treatment of nephrotic syndrome. Active drug ingredients include structurally related melanocortin peptides that bind to cell surface G-protein-coupled receptors known as melanocortin receptors, which are expressed in glomerular podocytes. In animal models of membranous nephropathy, stimulation has been demonstrated to reduce podocyte injury and loss. We hypothesized that H.P. Acthar® Gel would improve symptoms of the nephrotic syndrome in patients with idiopathic membranous nephropathy. MethodsTwenty patients received a subcutaneous dose of 40 or 80 IU twice weekly. Changes in proteinuria, albumin, cholesterol profile, estimated glomerular filtration rate and serum anti-PLA2R antibodies were assessed at baseline and in response to treatment along with tolerance and safety. ResultsBaseline characteristics included mean proteinuria (9.1 ± 3.4 g/day), albumin (2.7 ± 0.8 g/dL), estimated glomerular filtration rate (77 ± 30 mL/min) along with elevated total and low-density lipoprotein (LDL) cholesterol. By 12 months of follow-up, there was a significant improvement in proteinuria in the entire cohort, decreasing to 3.87 ± 4.24 g/day (P < 0.001) with significant improvements in serum albumin, total and LDL cholesterol. A >50% decrease in proteinuria was noted in 65% of the patients with a trend toward better outcomes among patients who received greater cumulative doses. No significant adverse effects were documented. Clearing of serum anti-PLA2R antibodies prior to or in parallel with proteinuria improvement was noted in some, but not all patients. ConclusionsH.P. Acthar® Gel is a potential therapy for nephrotic syndrome secondary to idiopathic membranous nephropathy that deserves further study.

AB - BackgroundH.P. Acthar® Gel is currently the only Food and Drug Administration therapy approved for the treatment of nephrotic syndrome. Active drug ingredients include structurally related melanocortin peptides that bind to cell surface G-protein-coupled receptors known as melanocortin receptors, which are expressed in glomerular podocytes. In animal models of membranous nephropathy, stimulation has been demonstrated to reduce podocyte injury and loss. We hypothesized that H.P. Acthar® Gel would improve symptoms of the nephrotic syndrome in patients with idiopathic membranous nephropathy. MethodsTwenty patients received a subcutaneous dose of 40 or 80 IU twice weekly. Changes in proteinuria, albumin, cholesterol profile, estimated glomerular filtration rate and serum anti-PLA2R antibodies were assessed at baseline and in response to treatment along with tolerance and safety. ResultsBaseline characteristics included mean proteinuria (9.1 ± 3.4 g/day), albumin (2.7 ± 0.8 g/dL), estimated glomerular filtration rate (77 ± 30 mL/min) along with elevated total and low-density lipoprotein (LDL) cholesterol. By 12 months of follow-up, there was a significant improvement in proteinuria in the entire cohort, decreasing to 3.87 ± 4.24 g/day (P < 0.001) with significant improvements in serum albumin, total and LDL cholesterol. A >50% decrease in proteinuria was noted in 65% of the patients with a trend toward better outcomes among patients who received greater cumulative doses. No significant adverse effects were documented. Clearing of serum anti-PLA2R antibodies prior to or in parallel with proteinuria improvement was noted in some, but not all patients. ConclusionsH.P. Acthar® Gel is a potential therapy for nephrotic syndrome secondary to idiopathic membranous nephropathy that deserves further study.

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KW - nephrotic syndrome

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