System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Review Ahead of print 1 citation

PubMed: 42697978 DOI: 10.1038/s41581-026-01117-6

Inflammation as a therapeutic target to improve kidney and cardiovascular outcomes.

Nat Rev Nephrol

Authors: Katherine R Tuttle, Mehmet Kanbay, Radica Z Alicic, Juan Jesus Carrero, Sidar Copur, Ann Marie Navar, Brendon L Neuen, Vlado Perkovic, Peter Rossing, Nikolaus Marx, Paul M Ridker

Affiliations

  • Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA.
  • Nephrology Division, University of Washington School of Medicine, Seattle, WA, USA.
  • Division of Nephrology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.
  • Providence Medical Research Center, Providence Inland Northwest Health, Spokane, WA, USA.
  • Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Division of Nephrology, Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital, Stockholm, Sweden.
  • Department of Clinical Sciences, Danderyd Hospital, Danderyd, Sweden.
  • Department of Medicine (Cardiology), Southwestern Medical Center Dallas TX, Dallas, TX, USA.
  • The George Institute for Global Health, University of New South Wales Sydney, Sydney, Australia.
  • Steno Diabetes Center Copenhagen, Herlev, Denmark; University of Copenhagen, Copenhagen, Denmark.
  • Department of Internal Medicine I-Cardiology, Angiology and Internal Intensive Care Medicine (N.M.), RWTH Aachen University, Aachen, Germany.
  • Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

Chronic kidney disease (CKD) is a leading cause of premature death due to the loss of kidney function and development of kidney failure, and because of attendant major adverse cardiovascular events. High-sensitivity C-reactive protein (hsCRP), a biomarker of systemic inflammation, is associated with increased risks of cardiovascular events and CKD progression. CKD is characterized by a pro-inflammatory state with upregulation of inflammatory pathways and disruption of anti-inflammatory mechanisms. The resulting systemic inflammation, along with local tissue-based inflammatory mechanisms, are key contributors to kidney damage, atherosclerosis and cardiac dysfunction. As a result, a series of inflammatory pathways and mediators have emerged as potential therapeutic targets for CKD and its major cardiovascular complications. Investigational treatments that have targeted inflammation include inhibition of apoptosis signal-regulating kinase-1 (ASK1) by selonsertib, Janus kinase (JAK) 1/2 inhibition with baricitinib, protein kinase C-β (PKCβ) inhibition with ruboxistaurin, nuclear factor erythroid 2-related factor 2 (Nrf2) activation with bardoxolone, phosphodiesterase inhibition with pentoxifylline and monoclonal antibodies against IL-1β and IL-6. Furthermore, proven therapies for CKD, including renin-angiotensin-aldosterone system inhibitors, sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid antagonists, possess anti-inflammatory properties that might contribute to their previously established clinical benefits.

MeSH

Kidney Diseases, C-Reactive Protein, Kidney, Therapeutics