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

Extract

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.

Comment

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.