Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade

Journal of Clinical Medicine

Maria Vanessa Perez-Gomez¹  Maria Dolores Sanchez-Niño¹  Ana Belen Sanz¹  Catalina Martín-Cleary¹  Marta Ruiz-Ortega¹  Jesus Egido¹  Juan F. Navarro-González²  Alberto Ortiz¹  Beatriz Fernandez-Fernandez¹ 

[1] Division of Nephrology and Hypertension and FRIAT, IIS-Fundacion Jimenez Diaz, School of Medicine, UAM, Av Reyes Catolicos 2, 28040 Madrid, Spain; E-Mails:;REDINREN, Av Reyes Catolicos 2, 28040 Madrid, Spain

关键词: chronic kidney disease;    diabetes;    diabetic kidney disease;    inflammation;    interleukin-1-beta;    treatment;   

DOI  :  10.3390/jcm4061325

来源: mdpi

【 摘 要 】

Diabetic kidney disease is the most frequent cause of end-stage renal disease. This implies failure of current therapeutic approaches based on renin-angiotensin system (RAS) blockade. Recent phase 3 clinical trials of paricalcitol in early diabetic kidney disease and bardoxolone methyl in advanced diabetic kidney disease failed to meet the primary endpoint or terminated on safety concerns, respectively. However, various novel strategies are undergoing phase 2 and 3 randomized controlled trials targeting inflammation, fibrosis and signaling pathways. Among agents currently undergoing trials that may modify the clinical practice on top of RAS blockade in a 5-year horizon, anti-inflammatory agents currently hold the most promise while anti-fibrotic agents have so far disappointed. Pentoxifylline, an anti-inflammatory agent already in clinical use, was recently reported to delay estimated glomerular filtration rate (eGFR) loss in chronic kidney disease (CKD) stage 3–4 diabetic kidney disease when associated with RAS blockade and promising phase 2 data are available for the pentoxifylline derivative CTP-499. Among agents targeting chemokines or chemokine receptors, the oral small molecule C-C chemokine receptor type 2 (CCR2) inhibitor CCX140 decreased albuminuria and eGFR loss in phase 2 trials. A dose-finding trial of the anti-IL-1β antibody gevokizumab in diabetic kidney disease will start in 2015. However, clinical development is most advanced for the endothelin receptor A blocker atrasentan, which is undergoing a phase 3 trial with a primary outcome of preserving eGFR. The potential for success of these approaches and other pipeline agents is discussed in detail.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.