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Figure Legends
Figure 1.
Enrollment flow of study patients
*Ineligible due to exclusion criteria, such as non-adherence to treatment or withdrawal
of consent.
#excluded
Figure 2.
due to CVD events, death, or missing data.
Rates of each outcome among study patients according to their baseline ER
A. Cardiac events.
B. All-cause mortality.
C. MACE.
D. HF events.
ERI, erythropoietin resistance index; MACE, major adverse cardiovascular events; HF,
heart failure.
Figure 3.
Relationship between time-dependent ERI and each outcome
Fujii H, et al. page 32
ERI, erythropoietin resistance index; MACE, major adverse cardiovascular events
The colors of the bars represent the same ERI group for each outcome (low ERI group,
gray bar; middle ERI group, orange bar; and high ERI group, light blue bar).
Figure 4.
ERI changes during the study period
ERI, erythropoietin resistance index.
Fujii H, et al. page 33
Supplemental figures
Supplemental Figure 1 (Figure S1).
Changes in the prescription of iron-containing
medications during the study period
Supplemental Figure 2 (Figure S2).
Changes in TSAT during the study period
TSAT, transferrin saturation.
Supplemental Figure 3 (Figure S3).
Changes in the percentage of patients on on-line
HDF during the study period
HD, hemodialysis; HF, hemofiltration; HDF, hemodiafiltration.
Figure 1
Click here to access/download;Figure;PARAMOUNT HD (Figure 1) R1.pptx
Exclusion#
41 patients
Marginal Structural Model
Analysis Set
3,993 patients
Exclusion#
723 patients
Landmark Analysis Set
3,311 patients
Figure 2A
Click here to access/download;Figure;renamed_879f4.pptx
A Cardiac events
(%) 100
Survival Probability
99
98
97
96
95
94
93
92
91
90
ERI low
ERI medium
ERI high
Log-rank trend test p value 0.20
Log-rank test p value 0.44
Figure 2B
Click here to access/download;Figure;renamed_bb7b0.pptx
B All-cause mortality
(%) 100
Survival Probability
99
98
97
96
95
94
93
92
91
90
ERI low
ERI medium
ERI high
Log-rank trend test p value <.0001
Log-rank test p value <.0001
Figure 2C
Click here to access/download;Figure;renamed_c50c2.pptx
C MACE
(%) 100
Log-rank trend test p value 0.0049
Log-rank test p value 0.012
Survival Probability
99
98
97
96
95
94
93
92
91
90
ERI low
ERI medium
ERI high
Figure 2D
Click here to access/download;Figure;renamed_535e9.pptx
D Heart failure
(%) 100
Survival Probability
99
98
97
96
95
94
93
92
91
90
ERI low
ERI medium
ERI high
Log-rank trend test p value 0.169
Log-rank test p value 0.374
Figure 3
Click here to access/download;Figure;renamed_b598c.pptx
4.5
* P < 0.05
T1
T2
T3
95% Confidence Interval
Hazard Ratio for T1
3.5
2.5
1.5
0.5
Cardiac Disease Events
Total N=3,993
N=298
Mortality
N=371
MACE
N=435
Heart Failure Events
N=134
Figure 4
Click here to access/download;Figure;renamed_5d755.pptx
0.15
Low
Medium
High
(T1)
(T2)
(T3)
0.10
0.05
0.00
0 1
2 3 4
5 6 7 8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
(month)
Table 1(Editable version)
Click here to access/download;Table(Editable version);PARAMOUNT HD (Table 1).docx
Table 1. Baseline characteristics of patients
All
(n = 3,312)
Low ERI
(n = 1,104)
Medium ERI
(n = 1,104)
High ERI
(n = 1,104)
p-value
Age (year)
65.5 ± 11.9
63.3 ± 12.1
65.7 ± 11.8
67.6 ± 11.5
<.0001
Sex (male) (%)
2,110 (63.7)
763 (69.1)
700 (63.4)
647 (58.6)
<.0001
22.0 ± 3.7
22.8 ± 3.8
22.0 ± 3.7
21.2 ± 3.4
<.0001
Systolic BP (mmHg)
150.3 ± 21.7
150.2 ± 22.2
150.5 ± 21.5
150.2 ± 21.4
0.943
Diastolic BP (mmHg)
78.1 ± 13.6
79.7 ± 13.5
77.6 ± 13.5
77.1 ± 13.6
<.0001
Pulse pressure (mmHg)
72.2 ± 17.0
70.5 ± 17.1
72.9 ± 16.9
73.1 ± 16.8
<.001
HT (%)
2,656 (80.2)
871 (78.9)
886 (80.3)
889 (81.4)
0.592
DM (%)
1,373 (41.5)
466 (42.2)
465 (42.1)
442 (40.0)
0.503
CVD (%)
1,725 (52.1)
543 (49.2)
572 (51.8)
610 (55.3)
0.017
RAS-I (%)
1,716 (51.8)
512 (46.4)
597 (54.1)
607 (55.0)
<.0001
β-blocker (%)
287 (8.7)
105 (9.5)
89 (8.1)
93 (8.4)
0.452
Statin (%)
654 (19.7)
245 (22.2)
225 (20.4)
184 (16.7)
0.004
Antiplatelet (%)
1,440 (43.5)
484 (43.8)
448 (40.6)
508 (46.0)
0.035
Vitamin D (%)
1,591 (48.0)
550 (49.8)
519 (47.0)
522 (47.3)
0.350
Phosphate binder (%)
2735 (82.6)
950 (86.1)
896 (81.2)
889 (80.5)
<.001
BMI (kg/m2)
Calcium containing (%)
1,972 (59.5)
672 (60.9)
658 (59.6)
642 (58.2)
0.429
167 (5.0)
74 (6.7)
60 (5.4)
33 (3.0)
<.001
1,789 (54.0)
639 (57.9)
579 (52.4)
571 (51.7)
0.006
816 (24.6)
283 (25.6)
268 (24.3)
265 (24.0)
0.640
HD vintage (years)
7.9 ± 7.4
7.7 ± 7.3
7.7 ± 7.1
8.4 ± 7.7
0.037
HD time (hours)
11.5 ± 2.5
11.7 ± 2.4
11.6 ± 2.4
11.2 ± 2.7
<.0001
Online HDF (%)
450 (13.6)
170 (15.4)
143 (13.0)
137 (12.4)
0.215
3,041 (91.8)
1,022 (92.6)
1,030 (93.3)
989 (89.6)
0.032
Graft (%)
215 (6.5)
64 (5.8)
62 (5.6)
89 (8.1)
Catheter (%)
12 (0.4)
5 (0.5)
1 (0.1)
6 (0.5)
Others (%)
44 (1.3)
13 (1.2)
11 (1.0)
20 (1.8)
Kt/V
1.5 ± 0.3
1.5 ± 0.3
1.5 ± 0.3
1.5 ± 0.4
0.168
Hemoglobin (g/dL)
10.7 ± 1.0
10.9 ± 0.9
10.7 ± 1.0
10.4 ± 1.0
<.0001
Alb (g/dL)
3.7 ± 0.4
3.7 ± 0.4
3.7 ± 0.4
3.6 ± 0.4
<.0001
CRP (mg/dL)
0.4 ± 1.0
0.3 ± 0.9
0.3 ± 0.8
0.5 ± 1.1
<.0001
154.2 ± 34.1
157.4 ± 32.9
153.9 ± 33.9
151.4 ± 35.1
<.001
9.1 ± 0.8
9.1 ± 0.7
9.1 ± 0.7
9.1 ± 0.9
0.649
Iron containing (%)
Others (%)
Iron agents (%)
Type of blood access
A-V fistula (%)
T-Chol (mg/dL)
cCa (mg/dL)
P (mg/dL)
iPTH (pg/mL)
Fe (µg/dL)
Ferritin (ng/mL)
TSAT (%)
5.3 ± 1.3
5.4 ± 1.3
5.3 ± 1.4
5.2 ± 1.3
0.010
167.3 ± 146.1
170.0 ± 129.0
165.6 ± 146.8
166.3 ± 161.1
0.794
60.6 ± 26.6
62.0 ± 25.2
63.0 ± 27.2
57.2 ± 27.0
<.0001
111.1 ± 228.5
103.3 ± 130.2
121.8 ± 325.7
108.0 ± 181.2
0.149
24.9 ± 11.6
24.8 ± 10.9
25.5 ± 11.9
24.2 ± 12.1
0.046
BMI, body mass index; BP, blood pressure; HT, hypertension; DM, diabetes mellitus; CVD, cardiovascular disease; RAS-I, reninangiotensin-aldosterone inhibitor; HD, hemodialysis; HDF, hemodialysis filtration; A-V fistula, arteriovenous fistula; Alb, albumin; CRP,
C-reactive protein; T-Chol, total cholesterol; cCa, corrected calcium; P, phosphate; iPTH, intact parathyroid hormone; Fe, iron; TSAT,
transferrin saturation.
Values are presented as mean ± standard deviation.
Table 2(Editable version)
Click here to access/download;Table(Editable version);PARAMOUNT HD (Table 2).docx
Table 2. Cox regression analysis
Reference
Cardiac events
All-cause mortality
MACE
Heart failure
Tertile of ERI
HR
95% CI
p-value
Medium
1.04
0.71-1.53
0.82
High
1.06
0.72-1.58
0.76
Medium
1.36
0.94-1.97
0.10
High
1.48
1.03-2.13
0.03
Medium
1.37
0.99-1.90
0.05
High
1.31
0.94-1.84
0.11
Medium
1.02
0.56-1.86
0.94
High
1.12
0.62-2.04
0.71
Low
Low
Low
Low
MACE, major adverse cardiovascular events; ERI, erythropoietin resistance index; HR, hazard ratio; CI, confidence interval.
Table 3(Editable version)
Click here to access/download;Table(Editable version);PARAMOUNT HD (Table 3).docx
Table 3. The positive effect of iron containing medications and online HDF on ESA sensitivity
Estimate value
Standard error
Iron containing medications
-0.00198
0.000537
0.0002
Online HDF
-0.00188
0.000738
0.0158
HDF, hemodiafiltration.
...
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