Abstract and Introduction
Abstract
Purpose of Review: The objective of this review is to discuss if chronic kidney disease (CKD) leads to chronic heart failure (CHF), and does worsening CHF lead to CKD progression and how a new medication class can modify the risk of both outcomes.
Recent Findings: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are similarly effective on cardiovascular (CV) – and kidney-related outcomes in the presence of CV and CKD.
Summary: SGLT2 inhibitors can reduce the risk of CHF events and CKD progression, and may have synergistic effects in patients with cardiorenal syndrome.
Introduction
Chronic kidney disease (CKD) is a strong and independent risk factor for cardiovascular disease (CVD), and worsening CVD can lead to CKD progression. Through multiple mechanisms, CKD can drive accelerated atherosclerosis,[1] and cardiorenal physiology can certainly complicate heart failure (HF) and management. Studies have shown that patients undergoing dialysis have a 30-fold higher risk for deaths from CVD than the general population.[2] The prevalence of CVD in patients with CKD is about 63% compared to only 5.8% for non-CKD patients in the United States.[3]
HF is the leading cardiovascular (CV) complication in patients with CKD and as kidney function declines its prevalence increases. The treatment of HF in patients with CKD is unclear, as there is often a different phenotype (largely HF with preserved ejection fraction [HFpeF]), and patients with advanced CKD are routinely excluded from clinical trials of HF medications. Moreover, CKD often complicates HF due to poor renal perfusion, preexisting intrinsic renal disease, and as a result of the effects of medications used to treat HF.[4]
Therapies targeting Renin-Angiotensin Aldosterone System (RAAS) activation are recommended in the management of CV risk in patients with CKD. Recently studies evaluating the newest class of antihyperglycemic agents for the treatment of diabetes mellitus lead to the evaluation of CV safety which in turn revealed not only safety but efficacy is reducing CV and kidney outcomes.[5–7] This new class of medications is the sodium-glucose cotransporter-2 (SGLT2) inhibitors.
SGLT-2 receptors are located in the early proximal tubule and reabsorb 90% of filtered glucose. SGLT-1 is a low-capacity transporter that takes care of the other 10%.[8] SGLT-2 inhibitors have been shown to improve the glycemic control with a low risk of hypoglycemia, independently of insulin secretion.
In patients with diabetes, trials have shown that SGLT-2 inhibitors reduce the risk of all-cause mortality, other CV events and surprisingly these trials also showed a reduction in HF in patients with diabetes. This further showed very promising findings for the role of SGLT-2 inhibitors in improving outcomes in HF and CKD. The results of these trials emphasized the importance of the kidney–heart connection. In this context, recent trials results have shown equal efficacy of SGLT-2 inhibitors in preventing cardiorenal outcomes in patients with and without diabetes mellitus.[]