Effect of canagliflozin on renal and cardiovascular outcomes across different levels of albuminuria: Data from the CANVAS program

Brendon L. Neuen, Toshiaki Ohkuma, Bruce Neal, David R. Matthews, Dick De Zeeuw, Kenneth W. Mahaffey, Greg Fulcher, Qiang Li, Meg Jardine, Richard Oh, Hiddo L. Heerspink, Vlado Perkovic

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background If SGLT2 inhibitors protect the kidneys by reducing albuminuria as hypothesized, peoplewith 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] 30-300mg/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 m2 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 effectmodification 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.

Original languageEnglish
Pages (from-to)2229-2242
Number of pages14
JournalJournal of the American Society of Nephrology
Volume30
Issue number11
DOIs
Publication statusPublished - Jan 1 2019

All Science Journal Classification (ASJC) codes

  • Nephrology

Fingerprint Dive into the research topics of 'Effect of canagliflozin on renal and cardiovascular outcomes across different levels of albuminuria: Data from the CANVAS program'. Together they form a unique fingerprint.

  • Cite this

    Neuen, B. L., Ohkuma, T., Neal, B., Matthews, D. R., De Zeeuw, D., Mahaffey, K. W., Fulcher, G., Li, Q., Jardine, M., Oh, R., Heerspink, H. L., & Perkovic, V. (2019). Effect of canagliflozin on renal and cardiovascular outcomes across different levels of albuminuria: Data from the CANVAS program. Journal of the American Society of Nephrology, 30(11), 2229-2242. https://doi.org/10.1681/ASN.2019010064