Weekly Journal Scan: a legacy cardiorenal effect of empagliflozin in patients with chronic kidney disease?

This comment refers to ‘Long-Term Effects of Empagliflozin in Patients with Chronic Kidney Disease’ which was published in the New England Journal of Medicine, https://doi.org/10.1056/NEJMoa2409183. It is estimated that ∼700 million individuals are affected by CKD worldwide. Slowing CKD progression and preventing the development of end-stage kidney disease, dialysis, or kidney transplantation is crucial, due to their significant impact on quality of life, CV outcomes, and mortality.3 The SGLT2 inhibitors are emerging as an important disease-modifying therapy for these patients, preserving kidney function by reduction of glomerular hyperfiltration through tubuloglomerular feedback, a mechanism that operates independently of their effects on glycaemic control.4 Additional mechanisms underlying the cardiorenal benefits of SGLT2 inhibitors include a reduction in oxidative stress, down-regulation of proinflammatory and profibrotic pathways, modulation of mitochondrial function and autophagy, that may act in concert with improved blood pressure and glycaemic control.5 In patients with CKD, regardless of the presence or absence of diabetes, SGLT2 inhibitors were shown to improve renal and CV outcomes.1,6 The EMPA-KIDNEY trial demonstrated the beneficial cardiorenal effects of empagliflozin in a wide population of patients with CKD at increased risk of progressing to end-stage kidney disease, with or without diabetes, and/or albuminuria.1 However, the trial was stopped early for efficacy at an interim analysis, thereby limiting the duration of follow-up to 2 years.