PMID- 31530577 OWN - NLM STAT- MEDLINE DCOM- 20200601 LR - 20201101 IS - 1533-3450 (Electronic) IS - 1046-6673 (Print) IS - 1046-6673 (Linking) VI - 30 IP - 11 DP - 2019 Nov TI - Effect of Canagliflozin on Renal and Cardiovascular Outcomes across Different Levels of Albuminuria: Data from the CANVAS Program. PG - 2229-2242 LID - 10.1681/ASN.2019010064 [doi] AB - BACKGROUND: If SGLT2 inhibitors protect the kidneys by reducing albuminuria as hypothesized, people with type 2 diabetes mellitus (T2DM) with higher albuminuria should benefit more. METHODS: We conducted a post-hoc analysis of data from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, which randomized 10,142 participants with T2DM and high cardiovascular risk to canagliflozin or placebo. We assessed effects of canagliflozin on renal, cardiovascular, and safety outcomes by baseline albuminuria. The trial included 2266 participants (22.3%) with moderately increased albuminuria (urinary albumin/creatinine ratio [UACR] 30-300 mg/g) and 760 (7.5%) with severely increased albuminuria (UACR >300 mg/g) at baseline. RESULTS: Canagliflozin lowered albuminuria with greater proportional reductions in those with moderately and severely increased albuminuria (P heterogeneity<0.001). After week 13, canagliflozin slowed the annual loss of kidney function across albuminuria subgroups, with greater absolute reductions in participants with severely increased albuminuria (placebo-subtracted difference 3.01 ml/min per 1.73 m(2) per year; P heterogeneity<0.001). Heterogeneity for the renal composite outcome of 40% reduction in eGFR, ESKD, or renal-related death was driven by lesser effects in participants with moderately increased albuminuria (P heterogeneity=0.03), but no effect modification was observed when albuminuria was fitted as a continuous variable (P heterogeneity=0.94). Cardiovascular and safety outcomes were mostly consistent across albuminuria levels including increased risks for amputation across albuminuria subgroups (P heterogeneity=0.66). Greater absolute risk reductions in the renal composite outcome were observed in participants with severely increased albuminuria (P heterogeneity=0.004). CONCLUSIONS: The proportional effects of canagliflozin on renal and cardiovascular outcomes are mostly consistent across patients with different levels of albuminuria, but absolute benefits are greatest among those with severely increased albuminuria. CI - Copyright (c) 2019 by the American Society of Nephrology. FAU - Neuen, Brendon L AU - Neuen BL AUID- ORCID: 0000-0001-9276-8380 AD - The George Institute for Global Health, University of New South Wales, Sydney, Australia. FAU - Ohkuma, Toshiaki AU - Ohkuma T AD - The George Institute for Global Health, University of New South Wales, Sydney, Australia. FAU - Neal, Bruce AU - Neal B AD - The George Institute for Global Health, University of New South Wales, Sydney, Australia. FAU - Matthews, David R AU - Matthews DR AD - Oxford Centre for Diabetes, Endocrinology and Metabolism, Harris Manchester College, University of Oxford, Oxford, UK. FAU - de Zeeuw, Dick AU - de Zeeuw D AD - University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Mahaffey, Kenneth W AU - Mahaffey KW AD - Department of Medicine, Stanford Center for Clinical Research, Stanford University School of Medicine, Stanford, California. FAU - Fulcher, Greg AU - Fulcher G AD - Royal North Shore Hospital, Sydney, Australia; and. FAU - Li, Qiang AU - Li Q AD - The George Institute for Global Health, University of New South Wales, Sydney, Australia. FAU - Jardine, Meg AU - Jardine M AD - The George Institute for Global Health, University of New South Wales, Sydney, Australia. FAU - Oh, Richard AU - Oh R AD - Janssen Research & Development, LLC, Raritan, New Jersey. FAU - Heerspink, Hiddo L AU - Heerspink HL AD - The George Institute for Global Health, University of New South Wales, Sydney, Australia. AD - University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. FAU - Perkovic, Vlado AU - Perkovic V AD - The George Institute for Global Health, University of New South Wales, Sydney, Australia; vperkovic@georgeinstitute.org.au. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190917 PL - United States TA - J Am Soc Nephrol JT - Journal of the American Society of Nephrology : JASN JID - 9013836 RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0SAC974Z85 (Canagliflozin) SB - IM MH - Aged MH - Albuminuria/*drug therapy MH - Canagliflozin/adverse effects/*therapeutic use MH - Cardiovascular System/*drug effects MH - Diabetes Mellitus, Type 2/*drug therapy MH - Female MH - Glomerular Filtration Rate/*drug effects MH - Humans MH - Male MH - Middle Aged MH - Sodium-Glucose Transporter 2 Inhibitors/*therapeutic use PMC - PMC6830803 OTO - NOTNLM OT - SGLT2 inhibitor OT - albuminuria OT - canagliflozin OT - cardiovascular OT - renal EDAT- 2019/09/19 06:00 MHDA- 2020/06/02 06:00 PMCR- 2020/11/01 CRDT- 2019/09/19 06:00 PHST- 2019/01/21 00:00 [received] PHST- 2019/07/16 00:00 [accepted] PHST- 2019/09/19 06:00 [pubmed] PHST- 2020/06/02 06:00 [medline] PHST- 2019/09/19 06:00 [entrez] PHST- 2020/11/01 00:00 [pmc-release] AID - ASN.2019010064 [pii] AID - 2019010064 [pii] AID - 10.1681/ASN.2019010064 [doi] PST - ppublish SO - J Am Soc Nephrol. 2019 Nov;30(11):2229-2242. doi: 10.1681/ASN.2019010064. Epub 2019 Sep 17.