1. Vascular Calcification: Bones, Blood Vessels, and Outcomes Ravi Thadhani, MD, MPH Associate Professor of Medicine Harvard Medical School Massachusetts General Hospital Disclosures: Grant Support from Abbott

3. Courtesy of Kevin Martin, MD Calcified Plaque

4. Goodman WG et al, NEJM 2000

5. Schwarz et al, NDT Plaque Morphology in ESRD - Increased Media Thickness - Excess Calcification

6. Keelan et al, Circ 2000

7. London GM, JASN 2003

8. Okuno et al, AJKD 2007

9. DeLoach et al, NDT 2009 Aortic calcification and CVD events in Transplanted Patients

10. Haydar A et al, Kidney Int 2004

11. London GM, Kidney Int 2003

12. Klassen et al, JAMA 2002

13. Raggi P et al, Hypertension 2007

14. What has been linked with calcification? Ca P Ca X P Fetuin OPG LDL Matrix-Gla Protein hsCRP IL-6 TNF-  ??

15. CAC and Minerals…

16. Frequent dialysis reduces need for P binders, but is this the mechanism of benefit?

17. Normally, mesenchymal stem cells differentiate to adipocytes, osteoblasts, chondrocytes, and vascular smooth muscle cells (VSMC) Moe SM, JASN 2008

18. Kuro-o M et al, Nature 1997

19. Yumita et al, Tohuku J Exp Med 1996 Tsujikawa et al, Mol Endocrinol 2003

20. Tsujikawa H et al, Mol Endocrinol 2003

21. +D Users- D Users

22. All Groups CEU, CHB, and JPT +16% +21% p=0.0045 p=0.0036 Friedman, Afkarian, et al, In Press

23. Rodriguez M et al, Kidney Int 2008

24. Cardus A et al, JBMR 2007

25. CAC and LVH tightly linked

26. Who Progresses?

27. What do the Statin Data tell us? Fellström et al, NEJM 2009

28. 55 yo F on HD for 8 years, dies of a CVA IVST=1.4cm; EF 60%, Mod-Sev Concentric Hypertrophy

29. Circulation 2009

30. Some Ongoing Trials Examining Calcification in ESRD PRIMO I & II – Paricalcitol and LVH, MRI of Aorta Included Cinacalcet + Low Dose Vitamin D (ADVANCE Trial) P-Binders and CAC: Sevelamer, Phos-Lo, Fosrenol Bisphosphonates and Calcification and BMD Phosphate Control and Calcification

31. Conclusions Calcification and Outcomes linked? Can Calcification be Modified? What interventions accelerate/decelerate calcification? What Biomarkers do we follow?