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

Pivotal clinical trials have heralded several new classes of pharmacological agents focused on improving combined heart-kidney outcomes among patients with cardiovascular-kidney-metabolic syndrome. This review compiles the current evidence pertaining to the use of these novel, exciting classes of agents among kidney transplant recipients. Treatment with renin-angiotensin-aldosterone system inhibitors continues to remain the backbone of pharmacological management among kidney transplant recipients for several indications. Data from systematic reviews and meta-analyses support the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists with several comorbidities. However, evidence for both nonsteroidal and steroidal mineralocorticoid receptor antagonists and angiotensin receptor-neprilysin inhibitors is emerging and not adequate to support routine clinical use in kidney transplant recipients. Finally, data from randomized controlled trials on statins serve as a reminder of their impact in the metabolic milieu following kidney transplantation. Using the recently introduced paradigm of cardiovascular-kidney-metabolic syndrome, this review proposes that four pharmacological agents constitute the key pillars for improving downstream heart-kidney outcomes based on existing evidence - renin-angiotensin-aldosterone system inhibitors, statins, sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. Furthermore, this review highlights relevant practical drug interactions with immunosuppressants and considerations of tolerability of these agents among kidney transplant recipients. Finally, this review discusses specific management considerations for coronary heart disease, heart failure and atrial fibrillation with unique nuances applicable to kidney transplant recipients. There remains a critical need for randomized trials in this vulnerable population focused on improvement in combined heart-kidney outcomes.