{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T06:51:31Z","timestamp":1781679091972,"version":"3.54.5"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a cornerstone of heart failure (HF) therapy; however, landmark trials systematically excluded patients with severe renal impairment. Consequently, prescribing SGLT2i for HF patients with advanced chronic kidney disease (CKD stage 4) remains a clinical \u201cblind spot\u201d due to fears of acute kidney injury. This study aimed to evaluate the long-term efficacy and renal safety of SGLT2i in this vulnerable, real-world population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This single-center, retrospective observational cohort study evaluated HF patients with a baseline estimated glomerular filtration rate (eGFR) of 15\u201329\u2005mL\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      treated between January 2021 and December 2024. To minimize confounding by indication, a rigorous 1:1 propensity score matching (PSM) was performed. The primary efficacy outcome was a composite of heart failure hospitalization (HHF) or cardiovascular death. The primary safety outcome was major adverse kidney events (MAKE), defined as a sustained \u226540% eGFR decline, initiation of dialysis, or renal death. Long-term eGFR slopes were analyzed using linear mixed-effects models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following PSM, the final analysis cohort comprised 320 balanced patients (160 in the SGLT2i group and 160 in the control group), with a median baseline eGFR of 22.4\u2005mL\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      . Over a median follow-up of 2.1 years, the SGLT2i group demonstrated a 38% relative risk reduction in the primary efficacy composite outcome compared to controls (30.6% vs. 45.6%; adjusted HR 0.62, 95% CI 0.44\u20130.87,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.005). The incidence of the primary safety outcome (MAKE) was statistically comparable between the two groups (14.4% vs. 16.9%; adjusted HR 0.86, 95% CI 0.52\u20131.43,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.550), with no significant excess in severe acute kidney injury or hyperkalemia. Following an initial early \u201cdip\u201d in eGFR (\u22122.1\u2005mL\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      ), SGLT2i utilization was associated with a significantly shallower annualized eGFR decline trajectory compared to standard care (\u22121.2 vs. \u22123.5\u2005mL\/min\/1.73\u2005m\n                      <jats:sup>2<\/jats:sup>\n                      per year,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In high-risk, real-world HF patients complicated by advanced CKD (Stage 4), SGLT2i therapy appears to be associated with substantial cardiovascular benefits and may attenuate long-term renal function decline. These findings suggest that severe renal impairment should not instinctively preclude the utilization of this life-saving therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1849205","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T05:51:50Z","timestamp":1781675510000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Long-term efficacy and renal safety of SGLT2 inhibitors in patients with heart failure and advanced chronic kidney disease (stage 4): a propensity score-matched retrospective cohort study"],"prefix":"10.3389","volume":"13","author":[{"given":"Weihua","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Cardiology, Fugou Huimin Traditional Chinese Medicine Hospital","place":["Zhoukou, Henan, 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