PMID- 31815931
OWN - NLM
STAT- MEDLINE
DCOM- 20200220
LR  - 20200220
IS  - 1549-1676 (Electronic)
IS  - 1549-1277 (Print)
IS  - 1549-1277 (Linking)
VI  - 16
IP  - 12
DP  - 2019 Dec
TI  - Acute kidney injury and adverse renal events in patients receiving 
      SGLT2-inhibitors: A systematic review and meta-analysis.
PG  - e1002983
LID - 10.1371/journal.pmed.1002983 [doi]
LID - e1002983
AB  - BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent a new 
      class of oral hypoglycemic agents used in the treatment of type 2 diabetes 
      mellitus. They have a positive effect on the progression of chronic kidney 
      disease, but there is a concern that they might cause acute kidney injury (AKI). 
      METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of the 
      effect of SGLT2is on renal adverse events (AEs) in randomized controlled trials 
      and controlled observational studies. PubMed, EMBASE, Cochrane library, and 
      ClinicalTrials.gov were searched without date restriction until 27 September 
      2019. Data extraction was performed using a standardized data form, and any 
      discrepancies were resolved by consensus. One hundred and twelve randomized 
      trials (n = 96,722) and 4 observational studies with 5 cohorts (n = 83,934) with 
      a minimum follow-up of 12 weeks that provided information on at least 1 adverse 
      renal outcome (AKI, combined renal AE, or hypovolemia-related events) were 
      included. In 30 trials, 410 serious AEs due to AKI were reported. SGLT2is reduced 
      the odds of suffering AKI by 36% (odds ratio [OR] 0.64 [95% confidence interval 
      (CI) 0.53-0.78], p < 0.001). A total of 1,089 AKI events of any severity (AEs and 
      serious AEs [SAEs]) were published in 41 trials (OR 0.75 [95% CI 0.66-0.84], p < 
      0.001). Empagliflozin, dapagliflozin, and canagliflozin had a comparable benefit 
      on the SAE and AE rate. AEs related to hypovolemia were more commonly reported in 
      SGLT2i-treated patients (OR 1.20 [95% CI 1.10-1.31], p < 0.001). In the 
      observational studies, 777 AKI events were reported. The odds of suffering AKI 
      were reduced in patients receiving SGLT2is (OR 0.40 [95% CI 0.33-0.48], p < 
      0.001). Limitations of this study are the reliance on nonadjudicated safety 
      endpoints, discrepant inclusion criteria and baseline hypoglycemic therapy 
      between studies, inconsistent definitions of renal AEs and hypovolemia, varying 
      follow-up times in different studies, and a lack of information on the severity 
      of AKI (stages I-III). CONCLUSIONS: SGLT2is reduced the odds of suffering AKI 
      with and without hospitalization in randomized trials and the real-world setting, 
      despite the fact that more AEs related to hypovolemia are reported.
FAU - Menne, Jan
AU  - Menne J
AUID- ORCID: 0000-0003-0255-6590
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
FAU - Dumann, Eva
AU  - Dumann E
AUID- ORCID: 0000-0001-7378-2072
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
FAU - Haller, Hermann
AU  - Haller H
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
FAU - Schmidt, Bernhard M W
AU  - Schmidt BMW
AD  - Department of Nephrology and Hypertension, Hannover Medical School, Hannover, 
      Germany.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20191209
PL  - United States
TA  - PLoS Med
JT  - PLoS medicine
JID - 101231360
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Glucosides)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - HDC1R2M35U (empagliflozin)
SB  - IM
MH  - Acute Kidney Injury/*drug therapy
MH  - Benzhydryl Compounds/therapeutic use
MH  - Canagliflozin/therapeutic use
MH  - Diabetes Mellitus, Type 2/chemically induced/*drug therapy
MH  - Glucosides/therapeutic use
MH  - Humans
MH  - Hypoglycemic Agents/*adverse effects/therapeutic use
MH  - Sodium-Glucose Transporter 2 Inhibitors/*adverse effects/therapeutic use
PMC - PMC6901179
COIS- I have read the journal's policy and the authors of this manuscript have the 
      following competing interests: JM has received lecture fees from Boehringer 
      Ingelheim and Astra Zeneca. HH has received lecture fees, advisory board 
      Consultant fees, and Research funds from Boehringer Ingelheim and Astra Zeneca.
EDAT- 2019/12/10 06:00
MHDA- 2020/02/23 06:00
PMCR- 2019/12/09
CRDT- 2019/12/10 06:00
PHST- 2019/06/26 00:00 [received]
PHST- 2019/11/11 00:00 [accepted]
PHST- 2019/12/10 06:00 [entrez]
PHST- 2019/12/10 06:00 [pubmed]
PHST- 2020/02/23 06:00 [medline]
PHST- 2019/12/09 00:00 [pmc-release]
AID - PMEDICINE-D-19-02279 [pii]
AID - 10.1371/journal.pmed.1002983 [doi]
PST - epublish
SO  - PLoS Med. 2019 Dec 9;16(12):e1002983. doi: 10.1371/journal.pmed.1002983. 
      eCollection 2019 Dec.