ckd in individuals with ckd

CKD in individuals with CKD

Sylvia E. Rosas, MD, MSCEUniversity of Pennsylvania

Philadelphia VA Medical Center3/19/2011

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

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%

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

recipients 1988-1997

Ojo, KI 2000

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

• 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

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

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

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

Giachelli, KI 2009

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

Dialysis leads to VSMC apoptosisShroff et al . Circulation 2008

Dialysis leads to VSMC apoptosisShroff et al . Circulation 2008

Normal

heteropycnotic nuclei

Cytoplasmic vacuoles and

matrix vesicles

vesicular debris

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

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

Electron Beam TomographyElectron Beam Tomography

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 =

AtherosclerosisIntimal Calcification

Types of Vascular Calcification

Medial Calcification or Mönckeberg’s sclerosis

Association between CRP and WBC quintiles and coronary

calcification

Roe, Rosas, Atherosclerosis, 2010

Mortality and cardiovascular event free survival in patients with and without

CAC

Roe, Rosas, Atherosclerosis, 2010

No CAC

CAC

Coronary calcification predicts cardiovascular events and mortality

Roe, Rosas, Atherosclerosis, 2010

Change in CAC score over time in renal transplant recipients

Schankel, Rosas AJT 2007

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

Coronary calcification progression predicts cardiovascular events and

mortality

n = 87

Roe, Rosas, Atherosclerosis, 2010

Sylvia.rosas@uphs.upenn.edu