Targeting inflammation in diabetic kidney disease: early clinical trials.

Abstract

INTRODUCTION:

The age-standardized death rate from diabetic kidney disease increased by 106% from 1990 to 2013, indicating that novel therapeutic approaches are needed, in addition to the renin-angiotensin system (RAS) blockers currently in use. Clinical trial results of anti-fibrotic therapy have been disappointing. However, promising anti-inflammatory drugs are currently on phase 1 and 2 randomized controlled trials.

AREAS COVERED:

The authors review the preclinical, phase 1 and 2 clinical trial information of drugs tested for diabetic kidney disease that directly target inflammation as a main or key mode of action. Agents mainly targeting other pathways, such as endothelin receptor or mineralocorticoid receptor blockers and vitamin D receptor activators are not discussed.

EXPERT OPINION:

Agents targeting inflammation have shown promising results in the treatment of diabetic kidney disease when added on top of RAS blockade. The success of pentoxifylline in open label trials supports the concept of targeting inflammation. In early clinical trials, the pentoxifylline derivative CTP-499, the CCR2 inhibitor CCX140-B, the CCL2 inhibitor emapticap pegol and the JAK1/JAK2 inhibitor baricitinib were the most promising drugs for diabetic kidney disease. The termination of trials testing the anti-IL-1β antibody gevokizumab in 2015 will postpone the evaluation of therapies targeting inflammatory cytokines.

• Authors: Maria Vanessa Perez-Gomez, Maria Dolores Sanchez-Niño, Ana Belen Sanz, Binbin Zheng, Catalina Martín-Cleary, Marta Ruiz-Ortega, Alberto Ortiz, Beatriz Fernandez-Fernandez
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 25 Issue 9 Pg. 1045-58 (Sep 2016) ISSN: 1744-7658 [Electronic] England
• PMID: 27268955 (Publication Type: Journal Article, Review)

Chemical References

• Anti-Inflammatory Agents

Topics

• Anti-Inflammatory Agents (administration & dosage, adverse effects, pharmacology, therapeutic use)
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Diabetic Nephropathies (drug therapy, immunology, metabolism)
• Humans
• Molecular Targeted Therapy
• Renin-Angiotensin System (drug effects)
• Treatment Outcome