Rapid and Simultaneous Initiation of Guideline-Directed Kidney Therapies in Patients with CKD and Type 2 Diabetes

The global incidence of chronic kidney disease (CKD) continues to rise, with type 2 diabetes as a major contributor. At any stage of CKD, patients with concurrent CKD and type 2 diabetes are at heightened cardiovascular risk and have a greater likelihood of dying from cardiovascular causes than progressing to kidney failure. Consequently, the use of ‘four pillars’ of CKD therapy, including renin-angiotensin system inhibitors (RASi), sodium-glucose cotransporter 2 inhibitors (SGLT2i), nonsteroidal mineralocorticoid receptor antagonists (ns-MRA), and glucagon-like peptide-1 receptor agonists (GLP1-RAs), has been advocated to reduce cardiovascular-kidney risk. While these therapies can mitigate cardiovascular and kidney events when used individually, the residual risks of these events remain high across major clinical trials testing these therapies separately as well as in real-world clinical settings. This raises the question about when to optimally initiate these therapies, including strategies that start these agents in rapid sequence, or even simultaneously, in order to reduce long-term risk, thereby mirroring best-practices with rapid titration schedules in patients with heart failure. However, initiating all four therapies simultaneously in the setting of CKD has not yet been tested due to lack of data on safety and tolerability in this high risk population. Data regarding the safety profile of rapid sequence initiation remain limited. Therefore, our aim was to review the existing evidence on the safety profiles of guideline-recommended therapies and discuss the challenges associated with rapid sequence initiation of these treatments in patients with CKD.