Targeting Inflammatory, Fibrotic, Hemodynamic, and Metabolic Pathways in Chronic Kidney Disease: Emerging Pharmacotherapies and Precision Treatment Strategies

Chronic kidney disease (CKD) is a progressive and heterogeneous disorder that remains a major cause of premature mortality, cardiovascular morbidity, and kidney failure worldwide. Although renin–angiotensin system inhibitors, sodium–glucose cotransporter 2 inhibitors, and nonsteroidal mineralocorticoid receptor antagonists have improved outcomes, many patients continue to have residual albuminuria, declining estimated glomerular filtration rate, and elevated cardiovascular risk. This review summarizes recent advances in CKD pharmacotherapy, focusing on therapies targeting inflammatory, fibrotic, hemodynamic, endothelial, and metabolic pathways. Emerging approaches include glucagon-like peptide-1 receptor agonists, aldosterone synthase inhibitors, endothelin receptor antagonists, dual endothelin–angiotensin receptor antagonists, soluble guanylate cyclase modulators, anti-inflammatory therapies, anti-fibrotic agents, and metabolic modulators. Evidence from major outcome trials, including DAPA-CKD, EMPA-KIDNEY, FIDELIO-DKD, FIGARO-DKD, SONAR, PROTECT, and FLOW, supports a shift toward layered, mechanism-based therapy. However, implementation requires careful patient selection, monitoring for adverse effects such as hyperkalemia, fluid retention, gastrointestinal intolerance, hypotension, and hepatic safety. Future CKD management will likely integrate early detection, biomarker-guided risk stratification, genomics, digital health, and artificial intelligence to enable personalized, multi-targeted treatment strategies and improve long-term renal and cardiovascular outcomes globally.