The renaissance of corticotropin therapy in proteinuric nephropathies

Nat Rev Nephrol. 2011 Dec 6;8(2):122-8. doi: 10.1038/nrneph.2011.190.

Abstract

Refractory nephrotic syndrome continues to be a therapeutic challenge despite advances in immunosuppression and blockade of the renin-angiotensin-aldosterone cascade. Adrenocorticotropic hormone (ACTH), a pituitary neuroimmunoendocrine polypeptide, was widely used in the 1950s as an effective therapy for childhood nephrotic syndrome, but has since been replaced by synthetic glucocorticoid analogues. In addition to controlling steroidogenesis, ACTH also acts as an important physiological agonist of the melanocortin system. Clinical and experimental evidence now suggests that ACTH has antiproteinuric, lipid-lowering and renoprotective properties, which are not fully explained by its steroidogenic effects. ACTH therapy is effective in inducing remission of nephrotic syndrome in patients with a variety of proteinuric nephropathies, even those resistant to steroids and other immunosuppressants. This Perspectives article describes the biophysiology of ACTH, with an emphasis on its melanocortin actions, particularly in renal parenchymal cells, which could potentially explain the therapeutic effects of ACTH in nephrotic glomerulopathies.

Publication types

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

MeSH terms

  • Adrenocorticotropic Hormone / therapeutic use*
  • Animals
  • Hormones / therapeutic use*
  • Humans
  • Nephrotic Syndrome / complications
  • Nephrotic Syndrome / drug therapy*
  • Proteinuria / drug therapy*
  • Proteinuria / etiology
  • Treatment Outcome

Substances

  • Hormones
  • Adrenocorticotropic Hormone