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

CKD in individuals with CKD

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CKD in individuals with CKD. Sylvia E. Rosas, MD, MSCE University of Pennsylvania Philadelphia VA Medical Center 3/19/2011. Objectives. Brief overview of pathophysiology of CKD. All-cause Mortality and CV Events According to Estimated GFR Go, et al. NEJM 2004. CKD is prevalent in CVD. - PowerPoint PPT Presentation

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Page 1: CKD in individuals with CKD

CKD in individuals with CKD

Sylvia E. Rosas, MD, MSCEUniversity of Pennsylvania

Philadelphia VA Medical Center3/19/2011

Page 2: CKD in individuals with CKD

Objectives

• Brief overview of pathophysiology of CKD.

Page 3: CKD in individuals with CKD

All-cause Mortality and CV

Events According to

Estimated GFR Go, et al. NEJM 2004

Page 4: CKD in individuals with CKD

CKD is prevalent in CVD

Ix, et al., 2003; Anavekar, et al., 2004; Shlipak, et al., 2004, McClellan et al, 2006.

0

20

40

60

CADCrCl ≤60 mL/min

AMI GFR <60 mL/min

CHFGFR ≤60 mL/min

23%

46%

33%

Pat

ien

ts W

ith

CK

D (

%)

CVAGFR ≤60 mL/min

43%

Page 5: CKD in individuals with CKD

Cause of death with graft function (DWGF) among renal transplant

recipients 1988-1997

Ojo, KI 2000

Page 6: CKD in individuals with CKD

Dialysis Patients have higher Coronary Calcification Score compared to CAD

patients

Adapted from Braun J et al. Am J Kid Dis. 1996;27:394-401.

0

500

1000

1500

2000

2500

28-39 40-49 50-59 60-69

Age (years)

Mea

n C

oro

nar

y C

alci

um

Sco

re

CAD-no ESRDDialysis

Page 7: CKD in individuals with CKD

• 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

Page 8: CKD in individuals with CKD

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 < 60 ml/min/1.73m2 for > 3 mo, with or w/o kidney damage

Definition of CKD

Page 9: CKD in individuals with CKD

Vascular Calcification

Inductive vs. inhibitory process

Inductive process Inhibitory processPyrophosphate

MGP, Osteopontin and osteoprotegerin

Fetuin (a)

Smad 6

BMP2

Cbfa1

Phos, PTH and Vitamin D

Page 10: CKD in individuals with CKD

Stages of Chronic Kidney Disease (CKD)1

Description GFR (ml/min/1.73m2) 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)

Kidney damage with normal or increased GFR

> 90 1

Kidney damage with mild decrease in GFR

60-89* 2

Moderate decrease in GFR

30-59 3

Severe decrease in GFR 15-29 4

Kidney failure < 15 or dialysis 5

Page 11: CKD in individuals with CKD

Giachelli, KI 2009

Page 12: CKD in individuals with CKD

Ca load in the vessel wall is high in patients on dialysis

Shroff et al . Dialysis Induces Apoptosis and Vascular Calcification. Circulation. 2008;118;1748-1757.

Calcium accumulation in the vessel wall begins predialysis

Page 13: CKD in individuals with CKD

Dialysis leads to VSMC apoptosisShroff et al . Circulation 2008

Page 14: CKD in individuals with CKD

Dialysis leads to VSMC apoptosisShroff et al . Circulation 2008

Normal

heteropycnotic nuclei

Cytoplasmic vacuoles and

matrix vesicles

vesicular debris

Page 15: CKD in individuals with CKD

Risk Factors for Vascular Calcification in CKD

Risk Factor Intima Media

Dyslipidemia √

Advanced age √ √

HTN √ Reciprocal

Male √

Smoking √

Diabetes √ √

Inflammation √ (local) √ (systemic)

Goodman et al, AJKD 2004

Page 16: CKD in individuals with CKD

Risk Factors for Vascular Calcification in CKD

Risk Factor Intima Media

Reduced GFR √

Hypercalcemia √

Positive Ca balance √

Hyperphosphatemia √ √

PTH abnormalities

Vitamin D administration

Duration of treatment with dialysis

Goodman et al, AJKD 2004

Page 17: CKD in individuals with CKD

Electron Beam TomographyElectron Beam Tomography

Page 18: CKD in individuals with CKD

EBCT Coronary Calcium ScoringEBCT Coronary Calcium Scoring

Hn x-factor(Agatston Scoring)

130-199 1

200-299 2

300-399 3

>400 4

Area = 15 mmArea = 15 mm22

Peak CT = 450Peak CT = 450Score = 15 x 4 = 60Score = 15 x 4 = 60

Area = 8 mmArea = 8 mm22

Peak CT = 290Peak CT = 290Score = 8 x 2 = 16Score = 8 x 2 = 16

Total Score = Total Score =

Page 19: CKD in individuals with CKD

AtherosclerosisIntimal Calcification

Types of Vascular Calcification

Medial Calcification or Mönckeberg’s sclerosis

Page 20: CKD in individuals with CKD

Association between CRP and WBC quintiles and coronary

calcification

Roe, Rosas, Atherosclerosis, 2010

Page 21: CKD in individuals with CKD

Mortality and cardiovascular event free survival in patients with and without

CAC

Roe, Rosas, Atherosclerosis, 2010

No CAC

CAC

Page 22: CKD in individuals with CKD

Coronary calcification predicts cardiovascular events and mortality

Roe, Rosas, Atherosclerosis, 2010

Page 23: CKD in individuals with CKD

Change in CAC score over time in renal transplant recipients

Schankel, Rosas AJT 2007

Page 24: CKD in individuals with CKD

Annualized Rate of Change by Subject Categories

050

100150200250

All

No

calc

ifica

tion

Det

ecta

ble

calc

ifica

tion

Non

-pr

ogre

ssor

s

Pro

gres

sorsAg

atso

n s

core

un

its

ARC mean

ARC median

Schankel, Rosas AJT 2007

Page 25: CKD in individuals with CKD

Coronary calcification progression predicts cardiovascular events and

mortality

n = 87

Roe, Rosas, Atherosclerosis, 2010