Acute kidney injury and adverse renal events in patients receiving SGLT2-inhibitors: A systematic review and meta-analysis
Open Access
- 9 December 2019
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Medicine
- Vol. 16 (12), e1002983
- https://doi.org/10.1371/journal.pmed.1002983
Abstract
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). 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). 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.Keywords
This publication has 19 references indexed in Scilit:
- Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: Analysis of the FDA adverse event report system databaseNutrition, Metabolism and Cardiovascular Diseases, 2017
- Systematic review of prognostic prediction models for acute kidney injury (AKI) in general hospital populationsBMJ Open, 2017
- Can SGLT2 Inhibitors Cause Acute Renal Failure? Plausible Role for Altered Glomerular Hemodynamics and Medullary HypoxiaDrug Safety, 2017
- Sodium‐glucose co‐transporter‐2 inhibitors and risk of adverse renal outcomes among patients with type 2 diabetes: A network and cumulative meta‐analysis of randomized controlled trialsDiabetes, Obesity and Metabolism, 2017
- Acute kidney injury from SGLT2 inhibitors: potential mechanismsNature Reviews Nephrology, 2016
- Empagliflozin and Progression of Kidney Disease in Type 2 DiabetesNew England Journal of Medicine, 2016
- Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion InjuryPLOS ONE, 2016
- Acute kidney injury: short-term and long-term effectsCritical Care, 2016
- Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 DiabetesNew England Journal of Medicine, 2015
- World Incidence of AKIClinical Journal of the American Society of Nephrology, 2013