Guideline-Recommended Disease-Modifying Therapies for Patients with Cardiorenal Disease: A Call-to-Action Narrative Review.

Substantial gaps exist between recommendations for guideline-directed medical therapy (GDMT) for chronic kidney disease (CKD) and its use in real-world clinical practice. This includes suboptimal dosing of renin-angiotensin system inhibitors (RASi), low uptake of sodium-glucose co-transporter 2 inhibitors (SGLT2i) for CKD, and low uptake and/or transient use of potassium binders to manage RASi-induced hyperkalemia. Suboptimal RASi therapy deprives patients of the full cardiorenal benefits associated with RASi, and increases the risk of cardiorenal adverse events and mortality. Hyperkalemia can be managed and optimal RASi dosing can be continued by using novel potassium binders, such as sodium zirconium cyclosilicate or patiromer. Similarly, low uptake of SGLT2i might be associated with the concern of an accelerated decline in estimated glomerular filtration rate and, therefore, disease progression when initiating SGLT2i. Numerous clinical trials have demonstrated that adding SGLT2i to RASi therapy can improve clinical outcomes and prolong patient survival in CKD. The recently published Kidney Disease: Improving Global Outcomes (KDIGO) 2024 clinical practice guideline for the evaluation and management of CKD extends the recommendation of SGLT2i to individuals with CKD without diabetes, reinforces the cardiorenal benefits of optimized RASi, recommends the addition of newer drug classes in suitable patients with CKD, and notes the use of novel potassium binders to manage hyperkalemia and enable optimal use of GDMT. In doing so, the guideline targets achievement of the "quadruple aim" of GDMT in CKD, i.e., enabling optimal use of RASi and SGLT2i in most patients, along with nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists in diabetic kidney disease. This manuscript constitutes a call to action to raise awareness of the growing clinical and economic burdens of CKD and to promote a united approach to the early detection and optimal treatment of CKD through stricter adherence to GDMT.