Contemporary management of advanced chronic kidney disease: An evidence-based review.

Abstract

Chronic kidney disease (CKD) is a major contributor to global morbidity and mortality, traditionally managed through renin-angiotensin system (RAS) inhibition and supportive care. Recent therapeutic advances have transformed this landscape, offering targeted interventions that modify disease progression and improve cardiovascular and renal outcomes. This review summarizes emerging treatments across key domains of CKD management. Sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated robust cardiorenal benefits, particularly in patients with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors are now widely used in CKD and heart failure, including among non-diabetic populations. GLP-1 receptor agonists are approved for T2DM and cardiovascular risk reduction, with recent expansion to CKD in T2DM. Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), particularly finerenone, provide additional cardiorenal protection with a lower risk of hyperkalemia than traditional steroidal agents. In autosomal dominant polycystic kidney disease (ADPKD), tolvaptan remains the only approved disease-modifying therapy, with clinical trials and real-world data supporting its efficacy across a range of disease stages. Emerging regenerative strategies, including mesenchymal stem cell (MSC) therapy and xenotransplantation using genetically modified pig kidneys, have shown early promise in preclinical models and limited human studies. While further research is needed to optimize patient selection and long-term outcomes, these approaches represent important future directions in nephrology. Together, these developments mark a shift toward mechanism-based, precision therapies in CKD care. Internal medicine clinicians are pivotal in identifying appropriate candidates for these treatments and integrating evolving evidence into practice to improve patient outcomes.