Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria
- 22 February 2021
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Clinical Journal of the American Society of Nephrology
- Vol. 16 (3), 384-395
- https://doi.org/10.2215/cjn.15260920
Abstract
Background and objectives The kidney protective effects of renin-angiotensin system inhibitors are greater in people with higher levels of albuminuria at treatment initiation. Whether this applies to sodium-glucose cotransporter 2 (SGLT2) inhibitors is uncertain, particularly in patients with a very high urine albumin-to-creatinine ratio (UACR; ≥3000 mg/g). We examined the association between baseline UACR and the effects of the SGLT2 inhibitor, canagliflozin, on efficacy and safety outcomes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) randomized controlled trial. Design, setting, participants, & measurements The study enrolled 4401 participants with type 2 diabetes, an eGFR of 30 to 300 to 5000 mg/g. Using Cox proportional hazards regression, we examined the relative and absolute effects of canagliflozin on kidney, cardiovascular, and safety outcomes according to a baseline UACR of ≤1000 mg/g (n=2348), >1000 to 1000 to Pheterogeneity=0.55). Absolute risk reductions for kidney outcomes were greater in participants with higher baseline albuminuria; the number of primary composite events prevented across ascending UACR categories were 17 (95% CI, 3 to 38), 45 (95% CI, 9 to 81), and 119 (95% CI, 35 to 202) per 1000 treated participants over 2.6 years (Pheterogeneity=0.02). Rates of kidney-related adverse events were lower with canagliflozin, with a greater relative reduction in higher UACR categories. Conclusions Canagliflozin safely reduces kidney and cardiovascular events in people with type 2 diabetes and severely increased albuminuria. In this population, the relative kidney benefits were consistent over a range of albuminuria levels, with greatest absolute kidney benefit in those with an UACR ≥3000 mg/g. Clinical Trial registry name and registration number: ClinicalTrials.gov: CREDENCE, NCT02065791. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_02_22_CJN15260920_final.mp3This publication has 29 references indexed in Scilit:
- Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 DiabetesThe New England Journal of Medicine, 2015
- Antihypertensive agents for preventing diabetic kidney diseaseEmergencias, 2012
- Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohortsKidney International, 2011
- The definition, classification, and prognosis of chronic kidney disease: a KDIGO Controversies Conference reportKidney International, 2011
- Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohortsKidney International, 2011
- Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro- and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trialsNephrology Dialysis Transplantation, 2011
- Albuminuria and Kidney Function Independently Predict Cardiovascular and Renal Outcomes in DiabetesJournal of the American Society of Nephrology, 2009
- Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO)Kidney International, 2005
- Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and HospitalizationThe New England Journal of Medicine, 2004
- Proteinuria as a modifiable risk factor for the progression of non-diabetic renal diseaseKidney International, 2001