{"id":"fdc30ff5b355","type":"article","url":"https://hartvaat.nl/2022/08/09/renale-en-vasculaire-effecten-van-gecombineerde-sglt2-en-ace-remming/","title":"Renale en vasculaire effecten van gecombineerde SGLT2- en ACE-remming","title_en":"Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition.","category":"preventie","category_label":"Preventie","professions":["cardioloog","internist"],"tags":["canagliflozine","cardiorenal-behandelstrategie","chronische-nierziekte","cystatine-c","dapagliflozine","empagliflozine","fidelio-dkd","fidelity","figaro-dkd","flow-trial","ras-remmers","renale-denervatie","sglt2-remmers"],"journal":"Circulation","doi":"10.1161/CIRCULATIONAHA.122.059150","source_url":"https://doi.org/10.1161/CIRCULATIONAHA.122.059150","authors":["Yuliya Lytvyn","Karen Kimura","Nuala Peter","Vesta Lai","Josephine Tse","Leslie Cham","Bruce A Perkins","Nima Soleymanlou","David Z I Cherney"],"significance":7,"published":"2022-08-09","source_date":"2022-08-09","image":"","kennis":["https://hartvaat.nl/kennis/cardiometabool/bloedsuikerdoelen-cardiovasculair/","https://hartvaat.nl/kennis/cardiometabool/esc-richtlijn-diabetes-cvd-cardiometabool/"],"congress":"","summary_en":"This mechanistic study showed that empagliflozin combined with ramipril provides additive renal and vascular protective effects in type 2 diabetes, supporting the rationale for combining SGLT2 inhibitors with RAAS inhibitors for cardiorenal protection.","created":"2026-07-03T10:29:52Z","updated":"2026-07-03T13:28:59Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"Mechanistische studie toonde dat empagliflozine gecombineerd met ramipril additieve renale en vasculaire bescherming biedt bij type 1 diabetes. De combinatie verminderde albuminurie en intraglomerulaire druk meer dan elk middel apart, wat de rationale voor combinatietherapie versterkt.","abstract_original":"BACKGROUND: The cardiorenal effects of sodium-glucose cotransporter 2 inhibition (empagliflozin 25 mg QD) combined with angiotensin-converting enzyme inhibition (ramipril 10 mg QD) were assessed in this mechanistic study in patients with type 1 diabetes with potential renal hyperfiltration. METHODS: Thirty patients (out of 31 randomized) completed this double-blind, placebo-controlled, crossover trial. Recruitment was stopped early because of an unexpectedly low proportion of patients with hyperfiltration. Measurements were obtained after each of the 6 treatment phases over 19 weeks: (1) baseline without treatment, (2) 4-week run-in with ramipril treatment alone, (3) 4-week combined empagliflozin-ramipril treatment, (4) a 4-week washout, (5) 4-week combined placebo-ramipril treatment, and (6) 1-week follow-up. The primary end point was glomerular filtration rate (GFR) after combination treatment with empagliflozin-ramipril compared with placebo-ramipril. GFR was corrected for ramipril treatment alone before randomization. At the end of study phase, the following outcomes were measured under clamped euglycemia (4 to 6 mmol/L): inulin (GFR) and para-aminohippurate (effective renal plasma flow) clearances, tubular sodium handling, ambulatory blood pressure, arterial stiffness, heart rate variability, noninvasive cardiac output monitoring, plasma and urine biochemistry, markers of the renin-angiotensin-aldosterone system, and oxidative stress. RESULTS: Combination treatment with empagliflozin-ramipril resulted in an 8 mL/min/1.73 m2 lower GFR compared with placebo-ramipril treatment (P=0.0061) without significant changes to effective renal plasma flow. GFR decrease was accompanied by a 21.3 mL/min lower absolute proximal fluid reabsorption rate (P=0.0092), a 3.1 mmol/min lower absolute proximal sodium reabsorption rate (P=0.0056), and a 194 ng/mmol creatinine lower urinary 8-isoprostane level (P=0.0084) relative to placebo-ramipril combination treatment. Sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor combination treatment resulted in additive blood pressure-lowering effects (clinic systolic blood pressure lower by 4 mm Hg [P=0.0112]; diastolic blood pressure lower by 3 mm Hg [P=0.0032]) in conjunction with a 94.5 dynes × sex/cm5 lower total peripheral resistance (P=0.0368). There were no significant changes observed to ambulatory blood pressure, arterial stiffness, heart rate variability, or cardiac output with the addition of empagliflozin. CONCLUSIONS: Adding sodium-glucose cotransporter 2 inhibitor treatment to angiotensin-converting enzyme inhibitor resulted in an expected GFR dip, suppression of oxidative stress markers, additive declines in blood pressure and total peripheral resistance. These changes are consistent with a protective physiologic profile characterized by the lowering of intraglomerular pressure and related cardiorenal risk when adding a sodium-glucose cotransporter 2 inhibitor to conservative therapy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02632747."}