Primary Prevention of CKD for Heart and Kidney Health: Ready for Primetime?

Chronic kidney disease (CKD) affects more than 850 million individuals worldwide and is a major contributor to global morbidity and premature mortality. Most CKD burden arises from early stages of disease, when reductions in estimated glomerular filtration rate (eGFR) are modest and symptoms often absent. CKD and cardiovascular disease share a bidirectional relationship mediated by common risk factors and pathophysiologic pathways. Even mild reductions in eGFR or low-grade albuminuria are associated with adverse cardiovascular outcomes. Accumulating evidence suggests that primary prevention of CKD may be feasible. In this narrative review, we examine pharmacologic strategies with potential relevance to preventing incident CKD among individuals without established disease at baseline, defined by eGFR ≥60 mL/min/1.73 m2 and absence of albuminuria. Evidence derives largely from secondary and post hoc analyses of cardiovascular outcome trials evaluating sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), mineralocorticoid receptor antagonists (MRAs), and angiotensin receptor-neprilysin inhibitors (ARNIs). Across multiple trials, SGLT2 inhibitors consistently attenuate eGFR decline and reduce incident or progressive albuminuria, including among participants without CKD at baseline, providing the most consistent evidence supporting a potential role in primary prevention. GLP-1 RAs demonstrate similar but less uniform effects, driven largely by reductions in albuminuria. Evidence supporting MRAs and ARNIs for primary prevention is more limited and less consistent. Although randomized trials specifically designed to evaluate incident CKD are lacking, these findings suggest that therapies developed for cardiometabolic disease may modify early markers of kidney injury. A selective, risk-based approach to earlier intervention may represent an emerging strategy to preserve kidney health and reduce long-term cardiovascular and renal risk.