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Effect of SGLT-2 Inhibition on Acute Kidney Injury: A Systematic Review and Meta-Analysis
37 Pages Posted: 20 Jun 2019
More...Abstract
Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have a positive effect on the progression of chronic kidney disease, but there is a concern that they might cause acute kidney injury (AKI).
Purpose: Systematic review and meta-analysis of the effect of SGLT2i on renal adverse events (AE) in randomised controlled trials and controlled observational studies.
Data Sources: PubMed, EMBASE, Cochrane library and ClinicalTrials.gov were searched without date restriction until 4 April 2019.
Study Selection: 109 randomized trials (n=89783) with a minimum follow-up of 12 weeks and 5 observational studies (n=83934) that provided information on at least one adverse renal outcome (AKI, combined renal AE or hypovolemia related events) were included.
Data Extraction: Data extraction was performed using a standardized data form and any discrepancies were resolved by consensus.
Data Synthesis: In 28 trials 339 serious AEs due to AKI were reported. SGLT2i reduced the odds of suffering AKI by 32% (OR 0.68 [95% CI 0.55-0.85], p<0.001. A total of 997 AKI AEs were published in 36 trials (OR 0.76 [95% CI 0.67-0.87], p<0.001. Empagliflozin, dapagliflozin and canagliflozin had a comparable benefit on the SAE and AE rate. In the observational studies 777 AKI events were reported. SGLT2i had a protective effect (OR 0.40 [95% CI 0.33-0.48], p<0.001). AEs related to hypovolemia were more commonly reported in SGLT2i treated patients (OR 1.22 [95% CI 1.11-1.35], p<0.001).
Limitations: This analysis is based on non-adjudicated safety endpoints and the severity of AKI (stage I-III) is not reported.
Conclusions: SGLT2i prevents AKI with and without hospitalisation in randomized trials and the real-world setting, despite the fact that more AEs related to hypovolemia are reported.
Funding Statement: The authors state: "No external funding."
Declaration of Interests: J. Menne has received lecture fees from Boehringer Ingelheim and Astra Zeneca; H. Haller has received lecture fees and research funds and has served on advisory boards for Boehringer Ingelheim and Astra Zeneca. E. Dumann and B. Schmidt have no conflict of interest.
Ethics Approval Statement: PRISMA diagram available.
Suggested Citation: Suggested Citation