Novel Therapies in Diabetic Kidney Disease and Risk of Hyperkalemia: A Review of the Evidence From Clinical Trials

Concerns about hyperkalemia may result in the underuse of established and novel therapies that improve kidney and/or cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). Hyperkalemia-related issues are of particular relevance in patients with CKD, who are commonly receiving other hyperkalemia-inducing agents such as renin-angiotensin-aldosterone system inhibitors and nonsteroidal mineralocorticoid receptor antagonists. In contrast, sodium/glucose transporter 2 (SGLT2) inhibitors mitigate the risk of serious hyperkalemia in clinical trials. We aim to review recent evidence surrounding the risk of hyperkalemia in patients with T2DM and CKD treated with established and novel therapies for diabetic kidney disease, focusing on SGLT2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists. We conclude that SGLT2 inhibitors can be used safely in patients with T2DM at high CV risk with CKD without increasing the risk of hyperkalemia. Routine potassium monitoring is generally required when finerenone is used as a kidney- and CV-protective agent in patients with T2DM. Based on existing data, when added to the standard of care, combining SGLT2 inhibitors with finerenone is safe and has the potential to exert additional cardiorenal benefits in patients with diabetic kidney disease. The use of potassium binders should be considered to enable optimal doses of guideline-based therapies for patients with diabetic kidney disease to maximize the kidney and CV benefits.