Heerspink, HJL;
Oshima, M;
Zhang, H;
Li, J;
Agarwal, R;
Capuano, G;
Charytan, DM;
... Jardine, MJ; + view all
(2022)
Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial.
American Journal of Kidney Diseases
, 79
(2)
244-256.e1.
10.1053/j.ajkd.2021.05.005.
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Abstract
RATIONALE AND OBJECTIVE: Canagliflozin reduced the risk of kidney failure and related outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) in the CREDENCE trial. This analysis of CREDENCE trial data examines the effect of canagliflozin on the incidence of kidney-related adverse events (AEs). STUDY DESIGN: A randomized, double-blind, placebo-controlled, multicenter, international trial. SETTING AND PARTICIPANTS: 4,401 trial participants with T2DM, CKD, and urinary albumin:creatinine ratio >300-5000mg/g. INTERVENTIONS: Participants were randomly assigned to receive canagliflozin 100mg/day or placebo. OUTCOMES: Rates of kidney-related AEs were analyzed using an on-treatment approach, overall and by screening estimated glomerular filtration rate (eGFR) strata (30-<45, 45-<60, and 60-<90 mL/min/1.73m2). RESULTS: Canagliflozin was associated with a reduction in the overall incidence rate of kidney-related AEs (60.2 vs 84.0 per 1,000 patient-years; hazard ratio [HR]: 0.71 [95% confidence interval (CI): 0.61, 0.82]; P<0.001), with consistent results for serious kidney-related AEs (HR: 0.72 [95% CI: 0.51, 1.00]; P=0.05) and acute kidney injury (AKI; HR: 0.85 [95% CI: 0.64, 1.13]; P=0.3). The rates of kidney-related AEs were lower with canagliflozin relative to placebo across the 3 eGFR strata (HRs of 0.73, 0.60, and 0.81 for eGFR 30-<45, 45-<60, and 60-<90 mL/min/1.73m2, respectively; P-interaction=0.3), with similar results for AKI (P-interaction=0.9). Full recovery of kidney function within 30 days after an AKI event occurred more frequently with canagliflozin versus placebo (53.1% vs 35.4%; odds ratio: 2.2 [95% CI: 1.0, 4.7]; P=0.04). LIMITATIONS: Kidney-related AEs including AKI were investigator-reported and collected without central adjudication. Biomarkers of AKI and structural tubular damage were not measured and creatinine data after an AKI event were not available for all participants. CONCLUSION: Canagliflozin compared to placebo was associated with a reduced incidence of serious and non-serious kidney-related AEs in patients with T2DM and CKD. These results highlight the safety of canagliflozin with regard to adverse kidney disease events.
| Type: | Article |
|---|---|
| Title: | Canagliflozin Reduces Kidney-Related Adverse Events in Type 2 Diabetes and CKD: Findings From the Randomized CREDENCE Trial |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1053/j.ajkd.2021.05.005 |
| Publisher version: | https://doi.org/10.1053/j.ajkd.2021.05.005 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Canagliflozin, SGLT2 inhibitor, drug safety, renal-related adverse events |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10129422 |
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