Targeting inflammation in diabetic kidney disease: early clinical trials.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.|b REDINREN , Madrid , Spain.
Maria Vanessa
MV
Perez-Gomez
a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.|b REDINREN , Madrid , Spain.
Maria Dolores
MD
Sanchez-Niño
a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.|b REDINREN , Madrid , Spain.
Ana Belen
AB
Sanz
a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.
Binbin
B
Zheng
a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.|b REDINREN , Madrid , Spain.
Catalina
C
Martín-Cleary
a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.|b REDINREN , Madrid , Spain.
Marta
M
Ruiz-Ortega
a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.|b REDINREN , Madrid , Spain.
Alberto
A
Ortiz
a Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine , UAM , Madrid , Spain.|b REDINREN , Madrid , Spain.
Beatriz
B
Fernandez-Fernandez
D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D012084:Renin-Angiotensin System / Q000187:drug effects*; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents
CCX140; Chemokine; chronic kidney disease; diabetes; diabetic kidney disease; inflammation; interleukin-1-beta; treatment