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