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Hjertekarsygdom ved kronisk nyreinsufficiens

Hjertekarsygdom ved kronisk nyreinsufficiens. Susanne Bro Rigshospitalet, København 5. Marts 2010. Kronisk nyresygdom. Ca. 4 % af befolkningen har kronisk nyresygdom stadium 3-5. Risiko for hjertekarsygdom er væsentligt øget ved kronisk nyresygdom.

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Hjertekarsygdom ved kronisk nyreinsufficiens

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  1. Hjertekarsygdom ved kronisk nyreinsufficiens Susanne Bro Rigshospitalet, København 5. Marts 2010

  2. Kronisk nyresygdom Ca. 4 % af befolkningen har kronisk nyresygdom stadium 3-5

  3. Risiko for hjertekarsygdom er væsentligt øget ved kronisk nyresygdom CV event: Hospitalization for CAD, HF, ischemic stroke, PAD Go et al, N Engl J Med 2004

  4. Karsygdom ved uræmi • Aterosklerose • Stive kar / vaskulære calcifikationer

  5. Hjertesygdom ved uræmi

  6. Uræmisk versus klassisk hjertekarsygdom • Unge patienter • Hurtig progression • Pludselig uventet hjertedød • Højere risiko for komplikationer • Ikke-klassiske risikofaktorer • Statiner virker ikke

  7. Risikofaktorer for hjertekarsygdom ved uræmi • Uræmi-specifikke • Anæmi • Hypervolæmi • Dyslipidæmi • Høj plasma fosfat • Høj PTH • Høj plasma homocysteine? • Inflammation • Oksidativt stress • Klassiske • Hypertension • Diabetes • Tobak • Høj plasma cholesterol • BMI • Fysisk inaktivitet

  8. En musemodel for uræmisk aterosklerose ApoE-/- mice J Am Soc Nephrol 2003

  9. Uræmi accelererer aterogenesen Uremic aorta Control aorta J Am Soc Nephrol 2003

  10. Er genekspressions-profilen anderledes i uræmiske arterier? Microarray Tissue RNA cRNA Uremic aorta

  11. Genekspressions-profiler:opregulering af inflammationsgener i karvæggen og nedregulering af gener relateret til muskelceller Inflammation Muscle structure Arterioscler Thromb Vasc Biol 2006

  12. Uræmi øger dannelsen af antistoffer mod oxideret LDL Arterioscler Thromb Vasc Biol 2007

  13. Effekten af RAS hæmning på uræmisk aterosklerose er uafhængig af blodtrykket Arterioscler Thromb Vasc Biol 2007

  14. Enalapril reducerer inflammation og oksidativt stress Arterioscler Thromb Vasc Biol 2007

  15. Renal Dysfunction Potentiates Foam Cell Formation by Repressing ABCA1 Yiqin Zuo, Patricia Yancey, Iris Castro, Wasif Khan, Masaru Motojima, Iekuni Ichikawa, Agnes B. Fogo, MacRae F. Linton, Sergio Fazio, Valentina Kon Methods and Results—We examined the impact of renal dysfunction on macrophage cholesterol homeostasis in theapoE_/_ mouse model of atherosclerosis. Renal impairment induced by uninephrectomy dramatically increased macrophage cholesterol content, linked to striking impairment of macrophage cholesterol efflux. This blunted efflux was associated with downregulation of the cholesterol transporter ATP-binding cassette transporter A1 (ABCA1) and activation of the nuclear factor-kappa B (NF-B). Treatment with the angiotensin receptor blocker (ARB) losartandecreased NF-B and restored cholesterol efflux. Conclusions—Our findings show that mild renal dysfunction perturbs macrophage lipid homeostasis by inhibitingcholesterol efflux, mediated by decreased ABCA1 transporter and activation of NF-B, and that ARB can restore cholesterol efflux. (Arterioscler Thromb Vasc Biol. 2009;29:1277-1282.)

  16. Konklusion og perspektiver • Uræmisk versus klassisk • hjertekarsygdom: • Andre patofysiologiske mekanismer • Inflammation og oksidativt stress ser ud til at spille en rolle • Mangel på kliniske RCTs

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