Evidence-Based Cardiovascular-Kidney-Metabolic Therapies in Kidney Transplant Recipients

Area of Science:

• Nephrology
• Cardiology
• Pharmacology

Background:

• Cardiovascular-kidney-metabolic (CKM) syndrome impacts kidney transplant recipients (KTRs).
• Novel pharmacological agents are being developed to improve combined heart-kidney outcomes in CKM syndrome.
• Evidence for these agents in KTRs is evolving.

Purpose of the Study:

• To review current evidence on novel pharmacological agents for KTRs with CKM syndrome.
• To identify key drug classes for improving heart-kidney outcomes in KTRs.
• To discuss drug interactions, tolerability, and specific cardiovascular conditions in KTRs.

Main Methods:

• Systematic review of pivotal clinical trials and meta-analyses.
• Analysis of evidence for renin-angiotensin-aldosterone system inhibitors, SGLT2 inhibitors, GLP-1 RAs, MRAs, ARNIs, and statins.
• Consideration of drug interactions with immunosuppressants and tolerability.

Main Results:

• Renin-angiotensin-aldosterone system inhibitors remain foundational.
• Sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists show support for use in KTRs with comorbidities.
• Evidence for mineralocorticoid receptor antagonists and angiotensin receptor-neprilysin inhibitors is insufficient for routine use.
• Statins demonstrate impact on the post-transplant metabolic milieu.

Conclusions:

• Four key pillars for improving heart-kidney outcomes in KTRs: RAAS inhibitors, statins, SGLT2 inhibitors, and GLP-1 RAs.
• Practical considerations include drug interactions and tolerability.
• Further randomized trials are needed to confirm benefits in this vulnerable population.