Leveraging melanocortin pathways to treat glomerular diseases

Adv Chronic Kidney Dis. 2014 Mar;21(2):134-51. doi: 10.1053/j.ackd.2013.09.004.


The melanocortin system is a neuroimmunoendocrine hormone system that constitutes the fulcrum in the homeostatic control of a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The kidney is a quintessential effector organ of the melanocortin hormone system with melanocortin receptors abundantly expressed by multiple kidney parenchymal cells, including podocytes, mesangial cells, glomerular endothelial cells, and renal tubular cells. Converging evidence unequivocally demonstrates that the melanocortin-based therapy using the melanocortin peptide adrenocorticotropic hormone (ACTH) is prominently effective in inducing remission of steroid-resistant nephrotic syndrome caused by various glomerular diseases, including membranous nephropathy, minimal change disease and focal segmental glomerulosclerosis, suggesting a steroidogenic-independent mechanism. Mechanistically, ACTH and other synthetic melanocortin analogues possess potent proteinuria-reducing and renoprotective activities that could be attributable to direct protection of glomerular cells and systemic immunomodulation. Thus, leveraging melanocortin signaling pathways using ACTH or novel synthetic melanocortin analogues represents a promising and pragmatic therapeutic strategy for glomerular diseases. This review article introduces the biophysiology of the melanocortin hormone system with an emphasis on the kidney as a target organ, discusses the existing data on melanocortin therapy for glomerular diseases, and elucidates the potential mechanisms of action.

Keywords: Adrenocorticotropic hormone; Glomerulopathy; Melanocortin; Nephrotic syndrome; Podocyte.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenocorticotropic Hormone / metabolism
  • Adrenocorticotropic Hormone / therapeutic use*
  • Cosyntropin / therapeutic use
  • Endothelial Cells / metabolism
  • Glomerulonephritis / complications
  • Glomerulonephritis / drug therapy*
  • Glomerulonephritis / metabolism
  • Glomerulonephritis, Membranous / drug therapy
  • Glomerulonephritis, Membranous / metabolism
  • Glomerulosclerosis, Focal Segmental / drug therapy
  • Glomerulosclerosis, Focal Segmental / metabolism
  • Hormones / therapeutic use*
  • Humans
  • Kidney / metabolism
  • Kidney Glomerulus / metabolism*
  • Melanocortins / metabolism
  • Melanocortins / therapeutic use
  • Mesangial Cells / metabolism
  • Nephrosis, Lipoid / drug therapy
  • Nephrosis, Lipoid / metabolism
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / etiology
  • Nephrotic Syndrome / metabolism
  • Podocytes / metabolism
  • Receptors, Melanocortin / agonists*
  • Receptors, Melanocortin / metabolism
  • Signal Transduction
  • alpha-MSH / analogs & derivatives
  • alpha-MSH / therapeutic use*


  • Hormones
  • Melanocortins
  • Receptors, Melanocortin
  • Cosyntropin
  • adrenocorticotropin zinc
  • alpha-MSH
  • Adrenocorticotropic Hormone