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
Patients With CKD (%)
60
46%
43%
40
33%
23%
20
0
CAD
CrCl ≤60 mL/min
AMI
GFR <60 mL/min
CHF
GFR ≤60 mL/min
CVA
GFR ≤60 mL/min
Ix, et al., 2003; Anavekar, et al., 2004; Shlipak, et al., 2004, McClellan et al, 2006.
Cause of death with graft function
(DWGF) among renal transplant
recipients 1988-1997
Ojo, KI 2000
Mean Coronary Calcium Score
Dialysis Patients have higher Coronary
Calcification Score compared to CAD
patients
2500
CAD-no ESRD
Dialysis
2000
1500
1000
500
0
28-39
40-49
50-59
60-69
Age (years)
Adapted from Braun J et al. Am J Kid Dis. 1996;27:394-401.
The people to test are those at greatest risk
• 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
Definition of 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
Vascular Calcification
Inductive vs. inhibitory process
Inductive process
Inhibitory process
BMP2
Pyrophosphate
Cbfa1
MGP, Osteopontin
and osteoprotegerin
Phos, PTH and
Vitamin D
Fetuin (a)
Smad 6
Stages of Chronic Kidney Disease (CKD)1
Description
GFR (ml/min/1.73m2)
Stage
Kidney damage with
normal or increased GFR
> 90
1
Kidney damage with mild
decrease in GFR
60-89*
2
Moderate decrease in
GFR
Severe decrease in GFR
30-59
3
15-29
4
Kidney failure
1(National
< 15 or dialysis
5
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)
Giachelli, KI 2009
Ca load in the vessel wall is high in patients
on dialysis
Calcium
accumulation
in the vessel
wall begins
predialysis
Shroff et al . Dialysis Induces Apoptosis and Vascular Calcification. Circulation. 2008;118;1748-1757.
Dialysis leads to VSMC apoptosis
Shroff et al . Circulation 2008
Dialysis leads to VSMC apoptosis
Shroff et al . Circulation 2008
heteropycnotic
nuclei
Normal
vesicular
debris
Cytoplasmic
vacuoles and
matrix
vesicles
Risk Factors for Vascular
Calcification in CKD
Risk Factor
Dyslipidemia
Advanced age
Intima
√
√
Media
HTN
Male
Smoking
Diabetes
Inflammation
√
√
√
√
√ (local)
Reciprocal
√
√
√ (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 Tomography
EBCT Coronary Calcium Scoring
Area = 15 mm2
Peak CT = 450
Score = 15 x 4 = 60
Area = 8 mm2
Peak CT = 290
Score = 8 x 2 = 16
Total Score = S
Hn x-factor
(Agatston Scoring)
130-199
1
200-299
2
300-399
3
>400
4
Types of Vascular Calcification
Atherosclerosis
Intimal 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
No CAC
CAC
Roe, Rosas, Atherosclerosis, 2010
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
P ro g re s s o rs
Non p ro g re s s o rs
D e te c ta b le
c a lc ific a tio n
No
c a lc ific a tio n
A ll
A g a ts o n s c o re u n its
A n n u alized R ate o f C h an g e b y S u b ject C ateg o ries
250
200
150
100
50
0
A R C m ean
A R C m edian
Schankel, Rosas AJT 2007
Coronary calcification progression
predicts cardiovascular events and
mortality
n = 87
Roe, Rosas, Atherosclerosis, 2010
Sylvia.rosas@uphs.upenn.edu