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

Courtesy of Kevin Martin, MD Calcified Plaque

Goodman WG et al, NEJM 2000

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

Keelan et al, Circ 2000

London GM, JASN 2003

Okuno et al, AJKD 2007

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

Haydar A et al, Kidney Int 2004

London GM, Kidney Int 2003

Klassen et al, JAMA 2002

Raggi P et al, Hypertension 2007

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

CAC and Minerals…

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

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

Kuro-o M et al, Nature 1997

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

Tsujikawa H et al, Mol Endocrinol 2003

+D Users- D Users

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

Rodriguez M et al, Kidney Int 2008

Cardus A et al, JBMR 2007

CAC and LVH tightly linked

Who Progresses?

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

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

Circulation 2009

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

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