Semin Nephrol. 2026 Jun 30:151689. doi: 10.1016/j.semnephrol.2026.151689. Online ahead of print.
ABSTRACT
Chronic kidney disease progresses through convergent mechanisms involving hemodynamic stress, proteinuria, inflammation, fibrosis, and metabolic disturbance. Barry Brenner's hyperfiltration hypothesis established these processes as drivers of ongoing injury, and landmark trials established that renin-angiotensin-aldosterone system (RAAS) inhibition slows progression and improves clinical outcomes, marking a shift from supportive care to disease-modifying treatment. Treatment options have since expanded, with newer therapeutic classes providing additional kidney and cardiovascular benefit alongside emerging agents with more targeted mechanisms of action. Approaches to prognostic assessment have also advanced through biomarkers, genetics, imaging, and digital tools, although integration into clinical practice remains incomplete. More than 4 decades after their introduction, RAAS inhibitors remain a core component of kidney protection, with newer therapies complementing rather than replacing them.
PMID:42379972 | DOI:10.1016/j.semnephrol.2026.151689