Horizon 2020 in diabetic kidney disease: The clinical trial pipeline for add-on therapies on Top of Renin Angiotensin System Blockade
EntityUAM. Departamento de Medicina
10.3390/jcm4061325Journal of Clinical Medicine 4 (2015): 1325-1347
Funded byThis work was supported by grants from Ministry of Science (SAF 2012-38830), FISEC07/90021, 10/0072, PI13/00047, PIE13/00051, ISCIII-RETICREDinRENRD12/0021FondosFEDER, Spanish Society of Nephrology, Comunidad de MadridS2010/BMD-2378, FRIAT-IRSIN, CIBERDEM, FP7 Diabeteskidneyconnect and PRIORITY. ISCIII Joan Rodes to BFF and Miguel Servet to ABS, MDSN. Programa Intensificación Actividad Investigadora (ISCIII/Agencia Laín-Entralgo/CM) to AO, Programa Intensificación Actividad Investigadora (ISCIII/SCS/Comunidad Autónoma Canarias) to JFNG.
ProjectGobierno de España. SAF 2012-38830; Gobierno de España. FISEC07/90021; Gobierno de España. PI13/00047; Gobierno de España. PIE13/00051; Comunidad de Madrid. S2010/BMD-2378/CIFRA
SubjectsChronic kidney disease; Diabetes; Diabetic kidney disease; Inflammation; Interleukin-1-beta; Treatment; Medicina
Rights© 2015 by the authors
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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
Google Scholar:Pérez-Gómez, María Vanessa - Sánchez Niño, María Dolores - Sanz, Ana Belén - Martín-Cleary, Catalina - Ruiz Ortega, Marta - Egido, Jesús - Navarro-González, Juan F. - Ortiz Arduán, Alberto - Fernández-Fernández, Beatriz
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