title: JAK inhibition in the treatment of diabetic kidney disease.
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 Finally, a yet unpublished Phase 2 multicentre, randomised, double-blind, placebo-controlled study of the efficacy of a selective JAK1 and JAK2 inhibitor has been conducted in type 2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 ).
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, 5520 MSRB1, 1150 W. Medical Center Dr., Ann Arbor, MI, 48109-5680, USA. fbrosius@umich.edu.|Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI, USA. fbrosius@umich.edu.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Brosius
authors.affiliation: Providence Health Care, University of Washington, Spokane, WA, USA.|The Kidney Research Institute, Division of Nephrology, University of Washington School of Medicine, Seattle, WA, USA.|The Institute of Translational Health Sciences, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Tuttle
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, 5520 MSRB1, 1150 W. Medical Center Dr., Ann Arbor, MI, 48109-5680, USA.|Department of Computational Medicine and Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
mesh_terms: D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053613:Janus Kinase 1 / Q000235:genetics / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D053616:Janus Kinase 3 / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000378:metabolism
chemical_list: D050791:STAT Transcription Factors; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D053616:Janus Kinase 3
keywords: Albuminuria; Clinical trial; Diabetes mellitus; Diabetic complications; Human; Mouse; Review; STAT