JAK inhibition in the treatment of diabetic kidney disease

Frank C. Brosius, Katherine R. Tuttle, Matthias Kretzler

Research output: Contribution to journalReview articlepeer-review

79 Scopus citations

Abstract

Diabetic kidney disease (DKD) is the most common cause of kidney failure in many countries today, but treatments have not improved in the last 20 years. Recently, systems biology methods have allowed the elucidation of signalling pathways and networks involved in the progression of DKD that were not well appreciated previously. A prominent pathway found to be integrally associated with DKD progression is the Janus kinase–signal transducer and activator of transcription (JAK–STAT) pathway. Increased expression of JAK–STAT genes was found in multiple cells in the kidney, including glomerular podocytes, in both early and progressive DKD. Subsequent experiments in a mouse diabetic model showed that enhanced expression of JAK2 selectively in glomerular podocytes increased functional and pathological features of DKD. Finally, a yet unpublished Phase 2 multicentre, randomised, double-blind, placebo-controlled study of the efficacy of a selective JAK1 and JAK2 inhibitor has been conducted in type 2 diabetic participants with DKD. In this trial there was a reduction of albuminuria in participants who received the active inhibitor compared with those who received a placebo These results support the further study of JAK inhibitors as a new therapy for DKD. This review summarises a presentation given at the ‘Anti-inflammatory interventions in diabetes’ symposium at the 2015 annual meeting of the EASD. It is accompanied by an overview by the Session Chair, Hiddo Heerspink (DOI: 10.1007/s00125-016-4030-4).

Original languageEnglish (US)
Pages (from-to)1624-1627
Number of pages4
JournalDiabetologia
Volume59
Issue number8
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Keywords

  • Albuminuria
  • Clinical trial
  • Diabetes mellitus
  • Diabetic complications
  • Human
  • Mouse
  • Review
  • STAT

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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