Effect of SGLT-2 inhibitors on acute kidney injury in patients with heart failure: a systematic review and meta-analysis.

ABSTRACT

BACKGROUND: Sodium glucose cotransporter-2 (SGLT-2) inhibitors are known to reduce hospitalization and cardiovascular mortality in various heart failure (HF) populations, potentially through enhanced excretion of water and sodium. However, there are concerns regarding the risk of acute kidney injury (AKI) associated with their use. This meta-analysis aimed to unravel the effects of SGLT-2 inhibitors on risk of AKI in a variety of patients with HF. METHODS: This study conducted a comprehensive literature search using PubMed, EMBASE, Cochrane Library, and clinicaltrials.gov for studies published up to January 1, 2024. Data were analyzed using both random-effects or fixed-effects models to estimate the overall relative risk (RR) with a 95% confidence interval (CI). RESULTS: Our analysis included 25,172 patients with HF from 16 randomized controlled trials. Treatment with SGLT-2 inhibitors led to a 28% reduction in the risk of AKI progression compared to placebo (RR 0.72, 95% CI 0.61-0.85, p<0.0001), without an increased risk of hypotension (RR 1.21, 95% CI 0.87-1.70, p = 0.26) and hypovolemia (RR 2.26, 95% CI 0.70-7.33, p = 0.17). Notably, SGLT-2 inhibitors significantly decreased AKI in specific subgroups, including patients with HF with reduced ejection fraction (RR 0.59, 95% CI 0.43-0.80, p = 0.0007), those treated with empagliflozin (RR 0.70, 95% CI 0.57-0.88, p = 0.002) or dapagliflozin (RR 0.74, 95% CI 0.57-0.98, p = 0.04), in studies with a follow-up of at least 1 year (RR 0.67, 95% CI 0.55-0.82, p = 0.0001), and in patients aged 65 years or older (RR 0.72, 95% CI 0.61-0.85, p < 0.0001). CONCLUSION: Use of SGLT-2 inhibitors did not increase the incidence of AKI regardless of the ejection fraction environment (chronic and acute), type of SGLT-2 inhibitors, or patient age.