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Rapid and Simultaneous Initiation of Guideline-Directed Kidney Therapies in Patients with CKD and Type 2 Diabetes
Ahmed Mustafa Rashid1, Muhammad Shahzeb Khan1,2,3, David Z I Cherney4
1Baylor Scott and White Research Institute, Baylor Scott and White Health, Dallas, Texas.
Insights
Chronic kidney disease (CKD) and type 2 diabetes increase cardiovascular risk. This review examines the safety of rapidly initiating four key CKD therapies to reduce this risk.
Area of Science:
- Nephrology
- Cardiology
- Endocrinology
Background:
- Global incidence of chronic kidney disease (CKD) is rising, significantly driven by type 2 diabetes.
- Patients with CKD and type 2 diabetes face elevated cardiovascular risk, often surpassing the risk of kidney failure.
- Current treatment guidelines advocate for a
- four pillars
- approach to CKD therapy to mitigate cardiovascular-kidney risk.
Purpose of the Study:
- To review the safety profiles of guideline-recommended therapies for CKD.
- To discuss challenges in the rapid sequence initiation of these therapies in patients with CKD.
- To address the need for data on simultaneous or rapid initiation strategies to reduce residual cardiovascular-kidney risk.
Main Methods:
- Literature review of existing evidence on the safety and tolerability of guideline-recommended CKD therapies.
- Analysis of data from clinical trials and real-world settings regarding individual and combined therapy use.
- Exploration of potential safety concerns and challenges associated with rapid sequence initiation of multiple agents.
Main Results:
- Individual therapies (renin-angiotensin system inhibitors, SGLT2 inhibitors, nonsteroidal MRA, GLP-1 RAs) show efficacy in mitigating cardiovascular and kidney events.
- Residual cardiovascular and kidney risks remain significant despite individual therapy use.
- Limited data exist on the safety and tolerability of rapid sequence or simultaneous initiation of all four therapeutic pillars in CKD patients.
Conclusions:
- Optimal timing for initiating the four pillars of CKD therapy remains an open question.
- Rapid sequence initiation strategies, mirroring heart failure management, may reduce long-term cardiovascular-kidney risk.
- Further research is needed to establish the safety and tolerability of rapid initiation protocols in high-risk CKD populations.
Abstract:
The global incidence of 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, sodium-glucose cotransporter 2 inhibitor, nonsteroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists, has been advocated to reduce cardiovascular-kidney risk. Although 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, 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.
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