{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:48:40Z","timestamp":1784224120755,"version":"3.55.0"},"reference-count":54,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiorenal Med"],"abstract":"<jats:p>Background: Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease and kidney failure worldwide. Over the past 3 decades, management has evolved from strict glycemic and blood pressure control to targeted therapies that modify disease progression. Summary: The DCCT\/EDIC (1993) confirmed the impact of intensive glycemic and multifactorial risk factor management. But the early 1990s established the foundation of nephroprotective therapy with the Captopril Trial (1993) in type 1 diabetes and subsequent IRMA-1 (2001), IDNT (2001), and the RENAAL (2001) studies established renin-angiotensin-system blockade as the first disease-specific therapy. More than a decade later, sodium-glucose cotransporter-2 (SGLT2) inhibitors transformed care, with EMPA-REG OUTCOME (2015) and CANVAS (2017) studies first demonstrating kidney benefits as secondary outcomes, which were confirmed in subsequent dedicated kidney trials: CREDENCE (2019), DAPA-CKD (2020), and EMPA-KIDNEY (2022) studies, demonstrating consistent reductions in kidney failure and cardiovascular mortality. Finerenone further advanced outcomes in FIDELIO-DKD (2020) and FIGARO-DKD (2021), and combination therapy with SGLT2 inhibition showed additive benefit in the CONFIDENCE (2025) study. Most recently, the FLOW (2024) trial confirmed glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as promising fourth pillar of nephroprotective therapies. Key Messages: Together, these advances, termed the \u201cFantastic Four,\u201d have redefined standards of care in DKD. This review synthesizes pivotal clinical trials and highlights evolving strategies to guide individualized treatment and future research.<\/jats:p>","DOI":"10.1159\/000550423","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T17:00:52Z","timestamp":1768323652000},"page":"44-57","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic Advances in Diabetic Kidney Disease: 30 Years of Evidence and the Rise of the \u201cFantastic Four\u201d in 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