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2013 .
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30 kDa
165
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-
1
Elliot S. et al. Exp. Hematology 2008; 36: 1573-1584
:
)
O2
HIF-1/pVHL
HIF –
Erslev & Beutler. Williams Hematology (fifth edition) 1995; 425–41
2
O2-
HIF
,
B12
:
(
)
)
-
O2
Hb
.
EPO
O2
precursor cells
Hb
3
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O2
Hb
.
EPO
precursor cells
O2
Hb
(%)
Hb <12
50
45
40
35
30
25
20
15
10
5
0
, Hb <11
;
44.1
5.2
1.8
1.3
90
/1.73
60-89
2)
30-59
15-29
Astor et al. Arch Intern Med. 2002;162:1401-1408
4
.
.
.
2008; 6: 41-47
5
D-
TNF-
Adapted from Silverberg et al. Kidney Int. 2003;64(Suppl 86):S40-S47
6
Hb
1.00
0.95
Hb
13.0 g/dL
0.90
12-12.9 g/dL
0.85
0.80
11-11.9 g/dL
<10 g/dL
0.75
10-10.9 g/dL
Log-rank test: P=0.0001
0.70
0
3 6
9 12 15 18 21 24 27 31 33 37
.
Hb
Levin et al. Nephrol Dial Transplant. 2006;21:370-377
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KDIGO 2012 .
Hb
,
,
):
TSAT
30%
500
,
8
,
Normal Hematicrit Study (
Canada-Europe Study (
CHOIR (
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CREATE (
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TREAT (
,
2
, III-IV
)–
CHOIR:
(
)
III-IV .
0.30
,
,
)
)
)
)
,
,
HB 13,5
Hb 13.5 g/dL
Hb 11.3 g/dL
0.25
0.20
0.15
0.10
: 125 vs 97
HR=1.34 (1.03–1.74)
Log rank test p=0.03
0.05
0.00
0
3
6
9
12 15 18 21 24 27 30 33 36 39
Month
1
2
715 654 587 520 457 355
717 660 594 539 499 397
270 176 101
293 182 107
72
67
55
44
23
23
Singh et al. N Engl J Med 2006;355:2085–2098
9
TREAT
1.
2
)
2.
3.
–
1,92
4.
(post-hoc
)
Pfeffer M. et al. N Engl J Med 2009; 3561 (21): 2019-2032
:
Hb
11.0-12.9 g/dL
n=58 058
5
MICS
3
(HR)
2
1
0.8
MICS=malnutrition-inflammation
complex syndrome
Hb (g/dL)
Regidor et al. J Am Soc
Nephrol. 2006;17:1181-1191
10
15972
,
:
11
Hb
-C
)
6
.
Hb
Gilbertson D.T. et al. Clin J Am Soc Nephrol 2008; 3:133-138
?
KDIGO 2012
3.4.1.
Hb 100
(2D)
3.4.2.
Hb
100
(2C)
3.4.3.
…
5
Hb
90 100
,
90
(2B)
Hb
3.4.5.
Hb
,
100
Hb,
(
)
KDIGO Anemia Work Group. KDIGO ClinicalPtactice Guideline for Anemia in
CKD. Kidney Int. Suppl. 2012:2: XXX-XXX.
11
Hb
III
105
.
??
105
?
ERBP: 11-12 g/dL (without intentionally
exceeding 13 g/dL)
K/DOQI: 11-12 g/dL (should not be greater
than 13 g/dL)
KDIGO 2012:
3.5.1.
115
(2C)
3.5.2.
,
115
,
130
(1A)
)
3.6.
,
12
(
)
Goodkin D.A. et al. J Am Soc Nephrol 2011; 22: 358–365
?
3.3.
(
)
(
,
–
(1B)
) (1B),
(2C)
[KDIGO 2012]
,
Hb<100 ,
,
,
Hb,
,
6-8
,
,
,
Rizzo J.D. et al. J Clin Oncol 2010; 28: 4996-5010
13
,
,
,
,
Sun C.H. et al. N Engl J Med 1989; 321: 151-157
14
Lorenz M. et al.
2002
438
39,7%
Vanrenterghem Y.
et al.
2003
4263
38,6%
Shibagaki Yu. et al.
2004
192
Imoagene-Oyedeji
A. et al.
2006
626
Chhabra D. et al.
2008
1023
2008
1280
.
20% (
)
72% (1
40% (3
20,3% (12
13% (Hb<11
.)
.)
.)
)
53%
,
:
3
.
15
-
,%
100
90
80
.- .
70
p < 0.002
60
Hct 30 (Hb 10 g/dl)
Hct > 30 (Hb > 10 g/dl)
50
40
0
2
6
10
14
18
22
26
)
Djamali A et al. Transplantation 2003; 76:816-20.
*
(n = 108)
(n = 231)
p
7 (6.9)
4 (1.7)
0.04
,
66.4 ± 18.7
70.7 ± 17.1
0.03
,
12 (11.1)
7 (3)
0.004
, n (%)
.
n (%)
*Hb < 13
, < 12
Kamar N, Rostaing L. Transplantation 2008; 85:1120-4.
16
12
.
1.0
p < 0.002
0.9
12
(n = 499)
.
(n = 127)
0.8
10
20
30
40
50
60
,
*Hb < 12
70
.
Imoagene-Oyedeji AE et al. J Am Soc Nephrol
2006; 17:3240-7.
KDIGO
22.2:
,
,
,
,
(Not graded)
Kidney Disease: Improving Global Outcomes (KDIGO)
Transplant Work Group. KDIGO clinical practice guideline for the
care of kidney transplant recipients.
American Journal of Transplantation 2009; 9(Suppl 3): S1–S157.
17
,
.
p
4/5 .
(n = 72)
(n = 72)
11.8 ± 1.5 g/dl
11.9 ± 1.2 g/dl
0.51
31%
19%
0.12
41%
79%
0.027
Hb
(Hb < 11 g/dl)
,
Akbari A et al. Nephron Clin Pract 2007; 107: c7-c13.
CAPRIT
,
,
(
)
Epoetin beta
13
*
n = 70
15 g/dl
R
10.5
.
n = 70
11.5 g/dl
24
.
*eCrCl < 50 ml/min/ 1.73 m2
18
(CAPRIT)
Hb
2
(eCrCl)
,
,
,
12,9
2
p
, n=62
, n=63
11,3
< 0,001
5,9
2,4
2
1,73
1,73
0,03
2
95%
80%
< 0,01
3
13
< 0,01
0
4
0,03
Choukroun G. et al. J Am Soc Nephrol 2012; 23(2): 360-368
(
6
.
)
Choukroun G. et al. J Am Soc Nephrol 2012; 23(2): 360-368
19
Hb
!
Hb
125
)
Hb
125
Hb
140
Heinze G. et al. BMG 2009; 339:b 4018
I.
(
)
(
)
II.
(
III. CERA (
)
)
IV.
(
,
)
20
,
> 130
B12,
./
,
,
,
,
,
:
,
,
KDIGO Anemia Work Group. KDIGO Clinical Ptactice Guideline for Anemia in
CKD. Kidney Int. Suppl. 2012:2: XXX-XXX.
®
~ 60 kDa
Macdougall IC, Eckhardt K-U. Lancet 2006; 368:947-53. Macdougall IC et al.
Poster presentation at ASN Congress 2003, San Diego, USA. J Am Soc Nephrol
2003; 14:769A. Abstract SU-PO1063. Jarsch M et al. Poster presentation at
ASH Congress 2006, Orlando, USA. Blood 2006; 108:452a. Abstract 1578.
21
,
=
:
1
(± SE)
)
1
1
2
3*
4
4,5
†
Mean (SD)
* CKD patients not on dialysis
6.8 ± 0.6
19.4 ± 2.5
8.8 ± 0.5
24.2 ± 2.6
25.3 ± 2.2
48.8 ± 5.2
-
69.6 (29.8)†
133 ± 9.8
137 ± 21.9
134 ± 19
139 ± 20
1. Halstenson et al. Clin Pharmacol Ther. 1991:50:702-12
2. Macdougall et al. J Am Soc Nephrol. 1999;10:2392-95
3. Padhi et al. Clin Pharmacokinet. 2006;45:503-10
4. Macdougall et al. Am J Kidney Dis. 2006;47:A41
5. Macdougall et al. J Am Soc Nephrol. 2005;16:759A
22
,
(ARCTOS)
Hb >13 g/dL
Hb
Mean (SD) Hb (g/dL)
Patients (%)*
16
15
14
13
12
11
10
9
8
7
40
P=0.0001
33,5
30
20
12,4
10
0
BL
1
2
3
4
5
6
* 1 Hb >13 g/dL
Q2W SC (n=162)
8
QW SC (n=162)
Macdougall et al. Clin J Am Soc Nephrol. 2008;3:337-47
:
Hb
?
(
)
Hb
?
23
1
.
)
.
300000000
140000
250000000
120000
)
100000
200000000
80000
150000000
60000
100000000
40000
50000000
20000
0
0
2008. 2009. 2010. 2011. 2012.
2008. 2009. 2010. 2011. 2012.
., 2013,
., 2013,
24
1
1
2000
.
3 166,9
6000
6 333
5 710
6000
11 420
75
8 822,22
75
8 822
100
11 245,08
100
11 245
4 822,64
120
19 291
30
., 2013,
200
64 000
12
– 6 * 11 245,08 = 67 470,48
(
16 000 = 1,3
12
. – 15,96
1,9
)
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. = 134 892,32
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( 67 422
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(
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)
.
3
)
2,5
., 2013,
25
Hb
ESA (
)
:
MAXIMA
PROTOS
RUBRA
STRIATA
: American Society of Nephrology 40th Annual
Meeting, October 31-November 5, 2007
Hb
ESA (
)
•
C.E.R.A.
,
,
• C.E.R.A.
Hb,
: American Society of Nephrology 40th Annual
Meeting, October 31-November 5, 2007
26
12
100
Hb
(
.2
)
100
Hb 120-125
.
Hb
10
Hb,
2
2
(1
,
,1
–
)
Hb
, 2012
,
*
,
27
., 30 .,
Hb 58 ,
,
40
< 50
,
,
,
.
,
,
., 52 ., .
, Hb 105 ,
., 44 .,
,
, Hb 65 ,
., 29
,
.
5, , Hb 95
., ,
.
5,
, Hb 91
., 34 .,
, 1,5
0,11
, Hb 100 ,
180
,
25
150
(
)
21
+++,
,
+
,
,
, Cr
–
,
-
+
(ESA)
Fe,
Hb
,
Hb
ESA
Hb
,
28
29