Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation and Study of Diabetic Nephropathy with Atrasentan : what was learned about the treatment of diabetic kidney disease with canagliflozin and atrasentan?
Fernández-Fernández, Beatriz (GEENDIAB)
Fernandez-Prado, Raul (GEENDIAB)
Górriz, Jose Luis (Hospital Clínic Universitari (València))
Martínez-Castelao, Alberto (Hospital Universitari de Bellvitge)
Navarro-González, Juan F. (Hospital Universitario Nuestra Señora de Candelaria (Santa Cruz de Tenerife))
Porrini, Esteban (Hospital Universitario de Canarias (La Laguna))
Soler, María José (Hospital Universitari Vall d'Hebron)
Ortiz, Alberto (GEENDIAB)
Universitat Autònoma de Barcelona

Date:	2019
Abstract:	In April 2019, two major Phase 3 randomized clinical trials were published that assessed primary renal outcomes in diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM). The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) tested an already available antidiabetic drug, canagliflozin, and the Study of Diabetic Nephropathy with Atrasentan (SONAR) tested a novel molecule, the endothelin-1 receptor blocker atrasentan, both on top of renin-angiotensin system blockade. Both trials demonstrated significant nephroprotection in patients with overt DKD (albuminuria >300 mg/g urinary creatinine) for combined primary endpoints of end-stage kidney disease (ESKD), doubling of serum creatinine or death from renal or cardiovascular causes in CREDENCE {hazard ratio [HR] 0. 70 [95% confidence interval (CI) 0. 59-0. 82]} and ESKD and doubling of serum creatinine in SONAR [HR 0. 65 (95% CI 0. 49-0. 88)]. Canagliflozin also decreased the secondary renal endpoint ESKD, doubling of serum creatinine or renal death [HR 0. 66 (95% CI 0. 53-0. 81)], which was similar in nature and impact to the primary endpoint in SONAR. In addition, canagliflozin decreased a secondary endpoint of cardiovascular death or hospitalization for heart failure [HR 0. 69 (95% CI 0. 57-0. 83)], whereas atrasentan had no significant impact on a secondary cardiovascular composite endpoint or on hospital admissions for heart failure and, despite restrictive exclusion criteria, there was a non-significant trend towards more frequent episodes of heart failure. Based on these results, canagliflozin will likely be approved for the indication of treating DKD in T2DM and the estimated glomerular filtration rate threshold for prescribing it will be lifted, whereas the future and place of atrasentan in the treatment of DKD remain unclear.
Grants:	Instituto de Salud Carlos III REDinRENRD016/000
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Albuminuria ; Atrasentan ; Canagliflozin ; Chronic kidney disease ; Diabetic kidney disease ; Endothelin ; Sodium-glucose cotransporter-2 (SGLT2) inhibitor
Published in:	Clinical Kidney Journal, Vol. 12 (may 2019) , p. 313-321, ISSN 2048-8513

DOI: 10.1093/ckj/sfz070
PMID: 31198532

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