Helical/Spiral CT. 2-4 slice 8-16 slice 16-32 slice 32-64 slice Helical/Spiral CT.
-
Upload
basil-fields -
Category
Documents
-
view
237 -
download
3
Transcript of Helical/Spiral CT. 2-4 slice 8-16 slice 16-32 slice 32-64 slice Helical/Spiral CT.
Helical/Spiral CT
2-4 slice
8-16 slice
16-32 slice
32-64 slice
Helical/Spiral CT
Arterial Calcification Increases Mortality Risk
‡Carotid artery, abdominal aorta, iliofemoral axis, and legs P<0.0001 for each increase in number of arteries calcified
n=110
1
Follow-up (months)
0
0.25
0.5
0.75
0 20 40 60 80
Pro
bab
ility
of
surv
ival
0 arteries‡ calcified
1 artery calcified
2 arteries calcified
3 arteries calcified
4 arteries calcified
73% mortalityin patients with4 arterial sites
calcified
Blacher J, Guerin AP, Pannier B et al. Hypertension 2001;38:938-942
Other Types of Calcification Predict Risk in CKD-5
Wang A, JASN 2003
Valve Calcification Predicts All-Cause Mortality and Cardiovascular Mortality in Peritoneal
Dialysis Patients
Wang AYM et al. JASN 2003
Follow-up time (months)
363024181260
Cumu
lative
Sur
vival
(%)
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
0.0
Valves calcifed
Both Mitral and
Aortic
Either Mitral or
Aortic
Neither
P<0.0005
Follow-up time (months)
363024181260
Cum
ulat
ive
Sur
viva
l (%
)
1.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
0.0
Valves Calcified
Both Mitral and
Aortic
Either Mitral or
Aortic
Neither
P<0.0005
All-Cause Mortality Cardiovascular Mortality
How Do these Methods Correlate?
Abdominal Aorta X-ray Score
ROC characteristics for a + abdominal X-ray score predicting a CACS> 30
Sensitivity= 0.74
Specificity= 0.77
L1
L2
L3
L4
Bellasi A. et al, KI 2006
Impacting Outcome in CKD
Sevelamer attenuates the progression of coronary artery and aorta calcification in
hemodialysis patients
Chertow GM, Burke SK, Raggi P, and the Treat to Goal Working Group
Kidney Int Vol 62; 2002
Treat-to-Goal Study Study Design
BL EBCT
Titrate dose:P=3.0-5.0 mg/dLCa <10.5 mg/dL
26 wk EBCT
Titrate dose:P=3.0-5.0 mg/dLCa < 10 mg/dL
PTH 150-300 pg/mL
Vitamin D if PTH >300 pg/mLIf P >5.5 mg/dL
2 weeks 12 weeks 40 weeks
Calcium binder Extended treatmentWashout
Extended treatmentSevelamerWashout
52 wk EBCT
Chertow GM et al. Kidney Int 2002;62:245-252
Randomize
Treat-to-Goal StudyBaseline Demographics
Smoker
Diabetes
BMI (kg/m2)
Sex (% male)
Time on dialysis (years)
Age (years)
8%
33%
26 ± 5
66%
2.9
56 ± 16
Calcium
3%
32%
26 ± 5
64%
3.6
57 ± 14
Sevelamer
Race (% white) 66% 71%
Chertow GM et al. Kidney Int 2002;62:245-252
Mea
n s
eru
m p
ho
sph
oru
s (m
g/d
L)
Treatment (weeks)
-3 -1 0 1 2 3 4 5 6 7 8 9 10 11 12 16 20 24 28 32 36 40 44 48 524.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
8.0Sevelamer (S): 6.5 g/day (~8 800 mg tablets) Calcium acetate (C): 4.6 g/day (~7 667 mg tablets)
S=5.1 C=5.1
Treat-to-Goal StudySerum Phosphorus
Chertow GM et al. Kidney Int 2002;62:245-252
Treat-to-Goal StudySerum Calcium
Study (weeks)
-2 0 3 6 9 12 16 20 24 28 32 36 40 44 48 52
10.5
10.0
9.5
9.0
8.5
S=9.50C=9.70
S = 9.40C = 9.30
Sevelamer Calcium
Chertow GM et al. Kidney Int 2002;62:245-252
Mea
n s
eru
m c
alci
um
(m
g/d
L)
Serum Ca x P Product
Study Week
-2 0 3 6 9 12 16 20 24 28 32 36 40 44 48 52
Ser
um C
alci
um x
Pho
spho
rus
Pro
duct
(m
mol
2 /L
2 )
3.5
4.0
4.5
5.0
5.5
6.0
6.5
S=5.72C=5.59
S=3.88C=4.00
Calcium Sevelamer
Treat-to-Goal StudyCoronary Artery and Aortic Calcification
CalciumSevelamer
Coronary artery Aorta
*Within treatment P<0.0001; between treatment groups P=0.02
Chertow GM et al. Kidney Int 2002;62:245-252
0
6
14*
25*
0
5
10
15
20
25
30
Week 26 Week 52
Med
ian
% c
han
ge
1
5
24*
28*
0
5
10
15
20
25
30
35
Week 26 Week 52
Me
dia
n %
ch
an
ge
Between group: P=0.03 (coronary), P=0.01 (aorta)
Sevelamer Calcium
Med
ian
ch
ang
e (%
)
-7%
0
10
20
30
40
60
70
90
20%
83%
66%
-10
-5
50
80
Coronary artery Aorta
P=NS
P=NS
P<0.0001
P<0.0001
Treat-to-Goal Study: 2-Year European Data Coronary Artery and Aortic Calcification
Asmus HG et al. NDT 2005; 20:1653-1661
“RIND trial”
Objective
The primary aims of this study were
To assess the degree of coronary artery calcification in a cohort of patients new to hemodialysis, and
To compare the impact of Sevelamer versus calcium containing phosphate binders on the development and progression of coronary artery calcification.
Block G et al Kidney International, Vol68(4): 1815-1824 (2005)
Materials and methods
Sevelamer Extended treatmentRANDOMIZEw/in 90 days
of HD
0 EBCT scan
Titrate doseP <6.5 mg/dL
Ca2+ <10.2 mg/dL
USUAL clinical practice
Calcium binder
Extended treatment
6 mo 12 mo 18 mo EBCT scans
Titrate doseP <6.5 mg/dL
Ca2+ <10.2 mg/dLPTH 150-300 pg/mL
Maintain dialysate Ca=2.5 mEq/L
•Renagel patients can receive Ca supplementation at night.•Dialysate Ca concentration was maintained at 2.5 mEq/l (1.25 mmol/l) throughout the study period.
Block G et al Kidney International, Vol68(4): 1815-1824 (2005)
Patients New to Dialysis and Established Patients
Prevalence of Coronary Calcification in CKD
*Russo D et al Am J Kidney Dis 2004;44:1024-1030 (CrCl =33 ml/min)**Spiegel D et al. Hemod Internat 2004: 8:265*** Chertow GM et al. Kidney Int 2002;62:245-252
40%*
57%**
83%***
0%
20%
40%
60%
80%
100%
Russo et al RIND TTG
Results: medication P-binders use:
– Of the 55 patients in the calcium arm, 38 received calcium carbonate only, 3 received calcium acetate only, and 14 received both medications during the 18-month study period.
– The average dose of Sevelamer was 8 g/day (10 pills), and the average dose of calcium was 5.75 g of CaCO3 or 9.2 g of Ca-acetate
Vitamin D use: slightly higher use in the Sevelamer group, but not statistically significant. Average doses were similar in both groups.
Statins: There were no statistically significant differences in the use of statins between the two groups.
Block G et al Kidney International, Vol68(4): 1815-1824 (2005)
Average Phosphorus Control by Binder
4.4
4.6
4.8
5.0
5.2
5.4
5.6
5.8
6.0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Study month
Ser
um
ph
osp
ho
rus
Renagel Calcium
Block, GA et al. Kidney Int 2005; 68:1815-1824
average dose 8 g/dayaverage dose elemental Ca 2.3 g/day
Mean Serum Calcium Level by Binder
8.5
8.7
8.9
9.1
9.3
9.5
9.7
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
Study month
Ser
um
cal
ciu
m (
alb
.co
rrec
ted
)
Renagel Calcium
Block, GA et al. Kidney Int 2005; 68:1815-1824
Results: Coronary Calcification
0
20
40
60
80
100
120
140
Sevelamer Ca Salts
SevelamerCa Salts
P<0.002
Block G et al Kidney International, Vol68(4): 1815-1824 (2005)
11x greater increase
Results: Median Coronary Artery Calcium Score
0
50
100
150
200
250
300
350
Baseline 6 months 12 months 18 months
Me
dia
n C
AC
S
Sevelamer Calcium
N=45
N=54N=55
N=51
N=53
N=45
N=47
N=40
N=45
Block G et al Kidney International, Vol68(4): 1815-1824 (2005)
Median Change in Total Coronary Artery Calcium Score by Diabetic Status-RIND
Sev
elam
er
Cal
cium
Sev
elam
er
Cal
cium
020406080
100120140160180
6 months
12 months
18 months
Diabetes
Med
ian
Ch
ang
e in
T
ota
l CA
CS
No Diabetes
PTH=293
PTH=229
P=0.038
P=0.015
Galassi A et al NDT 2006
Russo D, Kid Int, Advance Online, 5 September 2007
Progression of coronary artery calcification in predialysis patients with CaCO3 or Sevelamer
800P =0.001
P =0.001 NS
Initial
Final750
650
550
450
350
250
150
700
600
500
400
300
200
10050
0
Controls(n =29)
Sevelamer(n =27)
Calciumcarbonate(n =28)
TC
S
Figure 2: Initial (white bars) and final (dark bars) absolute TCS incontrols (n = 29) and in patients assigned to calcium carbonate(n = 28) and sevelamer (n =27). Numbers are mean and s.e.
Russo D, Kid Int, Advance Online, 5 September 2007
Annual progression of coronary artery calcification in predialysis patients
Controls(n=29)
Sevelamer(n=27)
Calciumcarbonate
(n=28)
TC
S
020406080
100120140160180200220240260280
320300
Figure 3: Annualized progression of TCS in controls (n = 29) and in patients assigned to calcium carbonate (n = 28) and sevelamer (n = 27).Numbers are mean and s.e.
RIND mortality
Baseline Coronary Artery ScoreIs a Strong Predictor of Mortality
0
20
40
60
80
100
Per
cen
t S
urv
ival
0
20
40
60
80
100
Per
cen
t S
urv
ival
Days
0 365 730 1095 1460 1825 2190
n=129
P=0.0035
Zero
<400
>400
Block GA et al. KI 2007
Increased Mortality in Patients Randomized to Calcium vs Sevelamer
0
20
40
60
80
100
Per
cen
t S
urv
ival
Days
0 365 730 1095 1460 1825 2190
n=129
P=0.0214
Sevelamer
Calcium
Cox Proportional Hazard Regression Model
Age
Race
Gender
Diabetes
Baseline CCS
Calcium vs. Sevelamer p=0.02 (HR 2.2)
Block GA et al. KI 2007
The Dialysis Clinical Outcomes Revisited (DCOR) Trial
Suki WN et al. Effects of Sevelamer and Calcium-Based Phosphate Binders on Mortality in Hemodialysis Patients
Kidney Int 2007;online Aug 29th
Study Design Primary study endpoint
– all-cause mortality
Secondary study endpoints
– cause-specific mortality (cardiovascular, infection, and other causes), and
– all-cause hospitalizations
Treatment interactions with each of the pre-defined prognostic factors were assessed: race, age (<65 or ≥65 years), sex, diabetes, primary cause of ESRD, and dialysis vintage
– a statistically significant interaction was required as a gating step prior to strata-specific subset analysis
Patient Disposition
*Did not discontinue from study prior to death or study cessation. In addition, 11 sevelamer patients and 18 calcium patients who discontinued early died during the 90-day follow-up period and were included in the mortality analyses (sevelamer, N=562; calcium, N=535).
RandomizedN = 2103
SevelamerN = 1053
Calcium-based binder N = 1050
Terminated Early (N=533)• Consent withdrawn (n=83)• Investigator decision (n=151)• Lost to follow-up (n=99)• Adverse event (n=50)• Renal transplant (n=46)• Changed dialysis modality (n=26)• Clinical site closure (n=19)• Other (n=70)
Completed study*N = 517
Terminated Early (N=502)• Consent withdrawn (n=69)• Investigator decision (n=94)• Lost to follow-up (n=108)• Adverse event (n=81)• Renal transplant (n=59)• Changed dialysis modality (n=22)• Clinical site closure (n=22)• Other (n=47)
Completed study*N = 551
All-Cause Mortality Overall Study Population
Time (Years)
Cu
mu
lati
ve I
nci
de
nce
of
All
-Cau
se M
ort
alit
y
CalciumSevelamer
1050 640 430 161 1053 656 449 196
No. at Risk
1 2 3 40
0.0
0.1
0.2
0.3
0.4
0.5
0.6
SevelamerCalcium
p = 0.40
HR = 0.93 (0.79 - 1.10)
For patients on treatment for 2 years, a difference between groups appears to emerge
(time-treatment interaction, p = 0.02)
All-Cause Mortality
0 1 2 3 40
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Time (Years)
Cu
mu
lati
ve I
nci
de
nce
of
All
-Cau
se M
ort
alit
y
p = 0.02
HR = 0.77 (0.61- 0.96)
Patients 65 Years
Time (Years)
1 2 3 400
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
SevelamerCalcium
p = 0.21
HR = 1.18 (0.91- 1.53)
Patients <65 Years
SevelamerCalcium
CalciumSevelamer
472 274 185 62 455 275 196 97
No. at Risk578 366 245 99 598 381 253 99
Multiple hospitalizations
1.7
1.9
1
1.5
2
Mu
ltip
le h
os
pit
aliz
ati
on
ra
te
(/p
ati
en
t-y
ea
r)Multiple hospitalizations
1.7
1.9
1
1.5
2
Mu
ltip
le h
os
pit
aliz
ati
on
ra
te
(/p
ati
en
t-y
ea
r)
A Comparison of Sevelamer and Calcium-Based Phosphate Binders on Hospitalization in Hemodialysis: Secondary
Analysis of DCOR Using Claims Data
Sevelamer Calcium
Unadjusted RR (referent: calcium) 0.90, P=0.03Adjusted RR* (referent: calcium) 0.89, P=0.02*Adjusted for demographic variables and prestudy cardiovascular comorbidity.
St. Peter W, Liu J, Weinhandl E, et al. AJKD 2008;51:445-454
Hospital Days
12.3
13.9
10
12
14
Ra
te f
or
ho
sp
ita
l da
ys
(/
pa
tie
nt-
ye
ar)
Hospital Days
12.3
13.9
10
12
14
Ra
te f
or
ho
sp
ita
l da
ys
(/
pa
tie
nt-
ye
ar)
Sevelamer Calcium
Unadjusted RR (referent: calcium) 0.88, P=0.05Adjusted RR* (referent: calcium) 0.88, P=0.03*Adjusted for demographic variables and prestudy cardiovascular comorbidity.
St. Peter W, Liu J, Weinhandl E, et al. AJKD 2008;51:445-454
A Comparison of Sevelamer and Calcium-Based Phosphate Binders on Hospitalization in Hemodialysis: Secondary
Analysis of DCOR Using Claims Data
What happened to the BONE?
Treat-to-Goal StudySerum Intact Parathyroid Hormone
Study (weeks)-2 0 12 16 20 24 28 32 36 40 44 48 52
0
50
100
150
200
250
300
350
400
Sevelamer Calcium
PTH below targetS=30%C=57%P=0.001
Chertow GM et al. Kidney Int 2002;62:245-252
Med
ian
ser
um
iP
TH
(p
g/d
L)
Time 0 1 & 2 Years f/u
Change in vertebral bone density
-8
-6
-4
-2
0
2
4
6
Sevelamer Calcium saltsTrabecularCortical
*
**P<0.05
%
ch
ang
e (h
ou
nsf
ield
un
its)
5%
2%
-7%
-2%
Raggi P. J Bone Min Res 2005;20:764-772
Total Hip Bone Mass Predicts Survival in Patients with CKD Stage 5
Survival (d)Survival (d)
14001400120012001000100080080060060040040020020000
Cu
mu
lati
ve S
urv
ival
Cu
mu
lati
ve S
urv
ival
1.01.0
0.80.8
0.60.6
0.40.4
0.20.2
NormalNormal
Osteopenia (T-score -1.0 – 2.5 SD)Osteopenia (T-score -1.0 – 2.5 SD)
Osteoporosis(T-score >-2.5 SD)Osteoporosis(T-score >-2.5 SD)
N=88P=0.03N=88P=0.03
Taal et al. Kidney Int. 2003;63: 1116-1120Taal et al. Kidney Int. 2003;63: 1116-1120
Summary
CVC is highly prevalent in CKD 5 CVC is linked with a poor prognosis in CKD 5 Sevelamer stopped progression of CVC in maintenance
HD pts (2002) Sevelamer inhibited progression of CVC in new
hemodialysis pts (2005) Sevelamer inhibited progression of CVC in pre-dialysis pts
(2007) Calcium salts were associated with reduced and
sevelamer with increased vertebral trabecular bone density (2005)
Renvela: New sevelamer “without” HCl and GI symptoms RIND: Sevelamer reduced mortality [HR: 2.2] (2007) DCOR: Pts >65 y/o treated w/ Sevelamer had fewer deaths,
fewer hospitalizations, lower overall cost of care (2008)
Wash-out up to 6 weeks
Sevelamer +/- Atorvastatin (N= 100 patients)
Ca Acetate + Atorvastatin (N= 103 patients)
EBCT Baseline EBCTWeek 26
1:1 randomization
Discontinuation of: all P-binders Ca supplements lipid-lowering agents vit D analogues
Randomized if: Serum P > 5.5 mg/dl LDL-C > 80 mg/dl Baseline EBCT score 30-
7000
P-binder: dose titration to achieve level of 3.5-5.5 mg/dl PTH target 150-300 pg/ml Dialysate Ca level maintained at 2.5 mEq/L throughout study
period
EBCTWeek 52
CARE-2 Study Design
Qunibi W, Moustafa M, Muenz LR, et al. AJKD. 2008
Chertow GM, Burke SK, Raggi P. Treat to Goal Working Group. Kidney Int. 2002;62:245-252.
0%
6%
14%
25%
0%
5%
10%
15%
20%
25%
30%
6 months 12 months
Med
ian
% C
han
ge
in C
AC
Sevelamer Calcium
*Within treatment P<0.001
*
*
Qunibi W, Moustafa M, Muenz LR, et al. AJKD. 2008; Advance On Line
n = sev 100 80 68 n = ca 103 71 58
*Significant within treatment
14%
30%
20%
29%
0%
5%
10%
15%
20%
25%
30%
35%
6 months 12 monthsM
edia
n %
Ch
ang
e in
CA
C
Sevelamer Calcium Acetate
CARE 2
**
*
*
Treat to Goal
Change in Coronary Artery Calcium Score
100
150
200
250
300
350
400
450
500
550
0 30 60 90 120
150
180
210
240
270
300
330
360
100
150
200
250
300
350
400
450
500
550
0 30 60 90 120150180210240270300330360
1. Chertow GM et al. Kidney Int. 2002;62:245-252;2. Qunibi W et al. Am J Kidney Dis. 2008; 51:952-965.
Treat to Goal CARE-2
Lo
g M
ean
iPT
H (
pg
/mL
)
Study day Study day
PTH Levels in TTG and CARE-2
SevelCalcium
Observed increase: 2.3%/y
Question 2
The administration of non-calcium-based phosphate binders results in slowing of cardiovascular calcification only in de novo dialysis patients
1. True
2. False
Question 2
The administration of non-calcium-based phosphate binders results in slowing of cardiovascular calcification only in de novo dialysis patients
1. True
2. False - CORRECT
Question 4
The multivariable adjusted mortality with sevelamer treatement in RIND was:
1. 3.1-fold higher than with calcium-based binders
2. 4.7-fold lower than with calcium-based binders
3. Not significantly different compared with calcium-based binders
4. 2.2-fold lower than calcium-based binders
Question 4
The multivariable adjusted mortality with sevelamer treatement in RIND was:
1. 3.1-fold higher than with calcium-based binders
2. 4.7-fold lower than with calcium-based binders
3. Not significantly different compared with calcium-based binders
4. 2.2-fold lower than calcium-based binders - CORRECT
Question 5
In the DCOR study, the progression of vascular calcification among calcium salts and sevelamer-treated patients was the same
1. True
2. False
Question 5
In the DCOR study, the progression of vascular calcification among calcium salts-treated and sevelamer-treated patients was the same
1. True
2. False - CORRECT
Question 6
In DCOR, the survival of patients above and below age 65 was a pre-specified end-point at the time of study design
1. True
2. False
Question 6
In DCOR, the survival of patients above and below age 65 was a pre-specified end-point at the time of study design
1. True - CORRECT
2. False
Question 7
At the conclusion of this meeting:
1. I know much more about the current issues regarding dialysis patients
2. I am EXTREMELY BORED with dialysis talks
3. I am going to the pharmacy IMMEDIATELY to buy Sevelamer for my own use!
4. I am going to leave my job and get a new one with Genzyme VenCAC
5. ……I want to be like RAGGI when I grow up!
Question 7
At the conclusion of this meeting:
1. I know much more about the current issues regarding dialysis patients
2. I am EXTREMELY BORED with dialysis talks
3. I am going to the pharmacy IMMEDIATELY to buy Sevelamer for my own use!
4. I am going to leave my job and get a new one with Genzyme VenCAC
5. ……I want to be like RAGGI when I grow up!
P Evenepoel, Kidney International (2007) 71, 376–379.
The Pleiotrophic Activites of SevelamerThe Pleiotrophic Activites of Sevelamer