Cardiorenal Benefits of SGLT2 Inhibitors in Patients with Chronic Kidney Disease and Concomitant Hypertension

Uncontrolled hypertension is both a driver of chronic kidney disease (CKD) and a complication of the disease, as well as a risk factor for cardiovascular disease (CVD). Therefore, renal protective agents with antihypertensive properties are desirable for management of cardiorenal syndrome in CKD. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are emerging as a new class of renal protective agents, with robust efficacy in delaying progression of CKD and reducing cardiovascular events. Here, we present an overview of SGLT2 inhibitors and discuss the alternative mechanisms contributing to the antihypertensive and cardiorenal benefits of SGLT2 inhibitors, with a focus on people with CKD and concomitant hypertension. We also explore the role of SGLT2 as a central node in the pathways underlying these mechanisms.

Beyond its well-known renal benefit, SGLT2 inhibitors have shown blood pressure (BP)-lowering effects in people with CKD, with an average reduction of 3-5 mm Hg in systolic BP. Clinical evidence has shown that SGLT2 inhibitors confer cardiorenal protective effects in patients with CKD regardless of diabetes status, and these benefits appear to extend to individuals with hypertensive CKD. The antihypertensive effects of SGLT2 inhibitors were also demonstrated in patients with CKD and hypertension. While osmotic diuresis is thought to be a predominant mechanism underlying the antihypertensive effects of SGLT2 inhibitors in the CKD population, we believe that the underlying mechanisms are likely to be multifactorial, with alternative pathways also involved, particularly in hypertension-associated CKD.

Given the rising incidence of hypertension and CKD, the BP-lowering and cardioprotective effects of SGLT2 inhibitors could provide additional value in using this drug class for management of patients with CKD who have hypertension. Further subgroup analyses or larger studies on this specific population will provide more insights into the role of SGLT2 inhibitors in improving cardiorenal outcomes in this setting.