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Published on: May 10, 2024
Targeting inflammation in diabetic kidney disease: early clinical trials
Maria Vanessa Perez-Gomez1,2, Maria Dolores Sanchez-Niño1,2, Ana Belen Sanz1,2
1a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.
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.
Insights
Novel anti-inflammatory drugs show promise for treating diabetic kidney disease (DKD) when used alongside current therapies. Promising agents include CTP-499, CCX140-B, emapticap pegol, and baricitinib.
Area of Science:
- Nephrology
- Pharmacology
- Inflammation Research
Background:
- Diabetic kidney disease (DKD) mortality has significantly increased, necessitating new treatments beyond current renin-angiotensin system (RAS) blockers.
- Anti-fibrotic therapies have yielded disappointing clinical results, shifting focus towards anti-inflammatory approaches.
Purpose of the Study:
- To review preclinical and clinical trial data of drugs targeting inflammation in diabetic kidney disease.
- To identify promising anti-inflammatory agents for DKD treatment.
Main Methods:
- Literature review of preclinical and Phase 1/2 clinical trials.
- Focus on drugs with inflammation as a primary or key mechanism of action.
- Exclusion of agents primarily targeting other pathways (e.g., endothelin, mineralocorticoid, vitamin D receptors).
Main Results:
- Anti-inflammatory agents demonstrate potential as adjunctive therapy for DKD on top of RAS blockade.
- Pentoxifylline's success in open-label trials supports targeting inflammation.
- CTP-499, CCX140-B, emapticap pegol, and baricitinib emerged as promising candidates in early trials.
Conclusions:
- Targeting inflammation offers a promising therapeutic strategy for diabetic kidney disease.
- Several agents, including CTP-499, CCX140-B, emapticap pegol, and baricitinib, warrant further investigation.
- Further research into anti-inflammatory therapies for DKD is crucial given the rising mortality rates.
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