Horizon 2020 in diabetic kidney disease: The clinical trial pipeline for add-on therapies on Top of Renin Angiotensin System Blockade
Entity
UAM. Departamento de MedicinaPublisher
MDPIDate
2015-06-18Citation
10.3390/jcm4061325
Journal of Clinical Medicine 4 (2015): 1325-1347
ISSN
2077-0383DOI
10.3390/jcm4061325Funded by
This 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.Project
Gobierno 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/CIFRAEditor's Version
http://dx.doi.org/10.3390/jcm4061325Subjects
Chronic kidney disease; Diabetes; Diabetic kidney disease; Inflammation; Interleukin-1-beta; Treatment; MedicinaRights
© 2015 by the authorsAbstract
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
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Google Scholar:Pérez-Gómez, María Vanessa
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Sánchez Niño, María Dolores
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Sanz, Ana Belén
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Martín-Cleary, Catalina
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Ruiz Ortega, Marta
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Egido, Jesús
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Navarro-González, Juan F.
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Ortiz Arduán, Alberto
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Fernández-Fernández, Beatriz
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