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Activation of the renin-angiotensin system (RAS) plays a central role in the pathogenesis of DKD by promoting intraglomerular hypertension, albuminuria, inflammation, oxidative stress, and progressive fibrosis. Angiotensin II-mediated efferent arteriolar constriction increases glomerular capillary pressure, while non-hemodynamic effects, including upregulation of transforming growth factor-\u03b2, NADPH oxidase-dependent reactive oxygen species generation, and podocyte apoptosis, contribute to structural kidney injury. Large, randomized trials have consistently demonstrated that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers reduce albuminuria, slow the glomerular filtration rate decline, and delay kidney failure across different stages of DKD. Evidence also supports cardiovascular benefits, including reduced heart failure events, in patients with DKD. A reduction in albuminuria is closely correlated with long-term kidney outcomes, underscoring its role as a mechanistic and therapeutic marker. Concerns regarding safety in advanced chronic kidney disease have been addressed by recent evidence indicating that routine discontinuation of RAS blockade does not improve kidney function and may increase cardiorenal risk. Although newer agents have expanded the therapeutic options, RAS inhibition remains the foundational therapy for DKD. This review summarizes the mechanistic basis, clinical evidence, safety considerations, and contemporary perspectives of RAS blockade in DKD.<\/jats:p>","DOI":"10.23876\/j.krcp.26.225","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T07:38:50Z","timestamp":1785224330000},"page":"867-875","update-policy":"https:\/\/doi.org\/10.23876\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Renin-angiotensin system blockade in diabetic kidney disease: an old pillar that still stands at the core of therapy"],"prefix":"10.23876","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0466-3664","authenticated-orcid":true,"given":"Dong 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