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CKD in individuals with CKD Sylvia E. Rosas, MD, MSCE University of Pennsylvania Philadelphia VA Medical Center 3/19/2011.

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Presentation on theme: "CKD in individuals with CKD Sylvia E. Rosas, MD, MSCE University of Pennsylvania Philadelphia VA Medical Center 3/19/2011."— Presentation transcript:

1 CKD in individuals with CKD Sylvia E. Rosas, MD, MSCE University of Pennsylvania Philadelphia VA Medical Center 3/19/2011

2 Objectives Brief overview of pathophysiology of CKD.

3 All-cause Mortality and CV Events According to Estimated GFR Go, et al. NEJM 2004

4 CKD is prevalent in CVD Ix, et al., 2003; Anavekar, et al., 2004; Shlipak, et al., 2004, McClellan et al, CAD CrCl ≤60 mL/min AMI GFR <60 mL/min CHF GFR ≤60 mL/min 23% 46% 33% Patients With CKD (%) CVA GFR ≤60 mL/min 43%

5 Cause of death with graft function (DWGF) among renal transplant recipients Ojo, KI 2000

6 Dialysis Patients have higher Coronary Calcification Score compared to CAD patients Adapted from Braun J et al. Am J Kid Dis. 1996;27: Age (years) Mean Coronary Calcium Score CAD-no ESRD Dialysis

7 Diabetes mellitus Hypertension Cardiovascular disease Family members of patients with ESRD Note on pediatric patients: –CKD may start with childhood obesity –No recommendations for routine testing The people to test are those at greatest risk

8 Kidney damage for > 3 mo, as defined by structural or functional abnormalities of the kidney, with or w/o decreased GFR, manifest by either Pathological abnormalities; or Markers of kidney damage, including abnormalities in the composition of the blood or urine, or abnormalities in imaging tests GFR 3 mo, with or w/o kidney damage Definition of CKD

9 Vascular Calcification Inductive vs. inhibitory process Inductive processInhibitory process Pyrophosphate MGP, Osteopontin and osteoprotegerin Fetuin (a) Smad 6 BMP2 Cbfa1 Phos, PTH and Vitamin D

10 Stages of Chronic Kidney Disease (CKD) 1 Description GFR (ml/min/1.73m 2 ) Stage 1 (National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Am J Kidney Dis 39[Suppl 1]: S1-S266, 2002)

11 Giachelli, KI 2009

12 Ca load in the vessel wall is high in patients on dialysis Shroff et al. Dialysis Induces Apoptosis and Vascular Calcification. Circulation. 2008;118; Calcium accumulation in the vessel wall begins predialysis

13 Dialysis leads to VSMC apoptosis Shroff et al. Circulation 2008

14 Normal heteropycnotic nuclei Cytoplasmic vacuoles and matrix vesicles vesicular debris

15 Risk Factors for Vascular Calcification in CKD Risk FactorIntimaMedia Dyslipidemia√ Advanced age√√ HTN√Reciprocal Male√ Smoking√ Diabetes√√ Inflammation√ (local)√ (systemic) Goodman et al, AJKD 2004

16 Risk Factors for Vascular Calcification in CKD Risk FactorIntimaMedia Reduced GFR √ Hypercalcemia √ Positive Ca balance √ Hyperphosphatemia √√ PTH abnormalities Vitamin D administration √ Duration of treatment with dialysis √ Goodman et al, AJKD 2004

17 Electron Beam Tomography

18 EBCT Coronary Calcium Scoring Hn x-factor (Agatston Scoring) >400 4 Area = 15 mm 2 Peak CT = 450 Score = 15 x 4 = 60 Area = 8 mm 2 Peak CT = 290 Score = 8 x 2 = 16 Total Score = 

19 Atherosclerosis Intimal Calcification Types of Vascular Calcification Medial Calcification or Mönckeberg’s sclerosis

20 Association between CRP and WBC quintiles and coronary calcification Roe, Rosas, Atherosclerosis, 2010

21 Mortality and cardiovascular event free survival in patients with and without CAC Roe, Rosas, Atherosclerosis, 2010 No CAC CAC

22 Coronary calcification predicts cardiovascular events and mortality Roe, Rosas, Atherosclerosis, 2010

23 Change in CAC score over time in renal transplant recipients Schankel, Rosas AJT 2007

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25 Coronary calcification progression predicts cardiovascular events and mortality n = 87 Roe, Rosas, Atherosclerosis, 2010

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