JAK inhibition in the treatment of diabetic kidney disease.
Authors Brosius FC, Tuttle KR, Kretzler M
Submitted By Matthias Kretzler on 7/13/2016
Status Published
Journal Diabetologia
Year 2016
Date Published
Volume : Pages 59 : 1624 - 7
PubMed Reference 27333885
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unpublished Phase 2 multicentre, randomised, double-blind, placebo-controlled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 ).

Investigators with authorship
Frank BrosiusUniversity of Arizona
Matthias KretzlerUniversity of Michigan