PMID- 34029680
OWN - NLM
STAT- MEDLINE
DCOM- 20220202
LR  - 20220202
IS  - 1523-6838 (Electronic)
IS  - 0272-6386 (Linking)
VI  - 79
IP  - 2
DP  - 2022 Feb
TI  - Canagliflozin and Kidney-Related Adverse Events in Type 2 Diabetes and CKD: 
      Findings From the Randomized CREDENCE Trial.
PG  - 244-256.e1
LID - S0272-6386(21)00626-0 [pii]
LID - 10.1053/j.ajkd.2021.05.005 [doi]
AB  - RATIONALE & 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 (Canagliflozin and Renal Events in Diabetes 
      with Established Nephropathy Clinical Evaluation) 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 & PARTICIPANTS: 
      4,401 trial participants with T2DM, CKD, and urinary albumin-creatinine ratio 
      >300-5,000 mg/g. INTERVENTIONS: Participants were randomly assigned to receive 
      canagliflozin 100 mg/d 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/1.73 
      m(2)). 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% 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/1.73 m(2), respectively; P = 0.3 for interaction), with similar results 
      for AKI (P = 0.9 for interaction). 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. CONCLUSIONS: Compared with placebo, canagliflozin 
      was associated with a reduced incidence of serious and nonserious kidney-related 
      AEs in patients with T2DM and CKD. These results highlight the safety of 
      canagliflozin with regard to adverse kidney-related AEs. FUNDING: The CREDENCE 
      trial and this analysis were funded by Janssen Research & Development, LLC, and 
      were conducted as a collaboration between the funder, an academic steering 
      committee, and an academic research organization, George Clinical. TRIAL 
      REGISTRATION: The CREDENCE trial was registered at ClinicalTrials.gov with 
      identifier number NCT02065791.
CI  - Copyright (c) 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All 
      rights reserved.
FAU - Heerspink, Hiddo J L
AU  - Heerspink HJL
AD  - The George Institute for Global Health, UNSW Sydney, Sydney, Australia; 
      Department of Clinical Pharmacy and Pharmacology, University of Groningen, 
      University Medical Center Groningen, Groningen, the Netherlands. Electronic 
      address: h.j.lambers.heerspink@umcg.nl.
FAU - Oshima, Megumi
AU  - Oshima M
AD  - The George Institute for Global Health, UNSW Sydney, Sydney, Australia; 
      Department of Nephrology and Laboratory Medicine, Kanazawa University, Kanazawa, 
      Japan.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Renal Division of Peking University First Hospital, Beijing.
FAU - Li, Jingwei
AU  - Li J
AD  - The George Institute for Global Health, UNSW Sydney, Sydney, Australia; 
      Department of Cardiology, Xinqiao Hospital, Army Military Medical University, 
      Chongqing, China.
FAU - Agarwal, Rajiv
AU  - Agarwal R
AD  - Indiana University School of Medicine and VA Medical Center, Indianapolis, IN.
FAU - Capuano, George
AU  - Capuano G
AD  - Janssen Research & Development, LLC, Raritan, NJ.
FAU - Charytan, David M
AU  - Charytan DM
AD  - Nephrology Division, NYU School of Medicine and NYU Langone Medical Center, New 
      York, NY; Baim Institute for Clinical Research, Boston, MA.
FAU - Craig, Jagriti
AU  - Craig J
AD  - Janssen Research & Development, LLC, Raritan, NJ.
FAU - de Zeeuw, Dick
AU  - de Zeeuw D
AD  - Department of Clinical Pharmacy and Pharmacology, University of Groningen, 
      University Medical Center Groningen, Groningen, the Netherlands.
FAU - Di Tanna, Gian Luca
AU  - Di Tanna GL
AD  - The George Institute for Global Health, UNSW Sydney, Sydney, Australia.
FAU - Levin, Adeera
AU  - Levin A
AD  - Division of Nephrology, University of British Columbia, Vancouver, BC, Canada.
FAU - Neal, Bruce
AU  - Neal B
AD  - The George Institute for Global Health, UNSW Sydney, Sydney, Australia; The 
      Charles Perkins Centre, University of Sydney, Sydney, Australia; Imperial College 
      London, London, United Kingdom.
FAU - Perkovic, Vlado
AU  - Perkovic V
AD  - The George Institute for Global Health, UNSW Sydney, Sydney, Australia; The Royal 
      North Shore Hospital, Sydney, Australia.
FAU - Wheeler, David C
AU  - Wheeler DC
AD  - The George Institute for Global Health, UNSW Sydney, Sydney, Australia; 
      Department of Renal Medicine, UCL Medical School, London, United Kingdom.
FAU - Yavin, Yshai
AU  - Yavin Y
AD  - Janssen Research & Development, LLC, Raritan, NJ.
FAU - Jardine, Meg J
AU  - Jardine MJ
AD  - The George Institute for Global Health, UNSW Sydney, Sydney, Australia; Concord 
      Repatriation General Hospital, Sydney, Australia.
LA  - eng
SI  - ClinicalTrials.gov/NCT02065791
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20210523
PL  - United States
TA  - Am J Kidney Dis
JT  - American journal of kidney diseases : the official journal of the National Kidney 
      Foundation
JID - 8110075
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0SAC974Z85 (Canagliflozin)
SB  - IM
MH  - Canagliflozin/adverse effects
MH  - *Diabetes Mellitus, Type 2/diagnosis/drug therapy/epidemiology
MH  - Double-Blind Method
MH  - Glomerular Filtration Rate
MH  - Humans
MH  - Kidney
MH  - *Renal Insufficiency, Chronic/diagnosis/epidemiology
MH  - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects
OTO - NOTNLM
OT  - Canagliflozin
OT  - SGLT2 inhibitor
OT  - acute kidney injury (AKI)
OT  - drug safety
OT  - kidney disease progression
OT  - kidney function
OT  - renal safety
OT  - renal-related adverse events
OT  - sodium/glucose cotransporter 2 (SGLT2)
OT  - type 2 diabetes mellitus (T2DM)
EDAT- 2021/05/25 06:00
MHDA- 2022/02/03 06:00
CRDT- 2021/05/24 20:24
PHST- 2020/09/02 00:00 [received]
PHST- 2021/05/06 00:00 [accepted]
PHST- 2021/05/25 06:00 [pubmed]
PHST- 2022/02/03 06:00 [medline]
PHST- 2021/05/24 20:24 [entrez]
AID - S0272-6386(21)00626-0 [pii]
AID - 10.1053/j.ajkd.2021.05.005 [doi]
PST - ppublish
SO  - Am J Kidney Dis. 2022 Feb;79(2):244-256.e1. doi: 10.1053/j.ajkd.2021.05.005. Epub 
      2021 May 23.