Патогенез МКН-ХБП и современные методы лечения

.,
.
:
(
2
)
R. Owen
1862 .
1880 . I. Sandstrom,
Uppsala (
(
)
)
F. Mandle
1925 .
»(
)
1883 . R. Lucas
1
3
XX
«
»,
1943 . S. Liu
C. Su
«
» ,
,
,
4
F. Albright
1937 .
,
45
,
H. Ellis (1997),
,
,
D. Sherrard
1993 .
,
20
,
5
)
2
5
.
,
,
,
,
KDIGO (Kidney
Diseases Improving Global Outcomes)
2006 .
CKD-MBD
(Chronic Kidney Disease-Mineral and Bone Disorder) –
(
,
),
6
D
3
7
1.
(
)
Na+ = H+
2.
)
3.
4.
Na+
5.
;
(
)
,
6.
8
1.
2.
4
D3
9
1.
2.
-
3.
D
: 7DBP
CH2
HO
D3
OH
D3
:
)
)
CH2
HO
25(OH)
:
D2
D3
, 25D)
OH
)
24-
CH2
OH
HO
,25(OH)2
,
, 1,25D)
D3
24-hydroxylase
24,25(OH)2D3
,24,25(OH)2D3
5
1
1
2+
1,25(OH)2D3
VD
R
R
R
R
2+
VD
1,25(OH)2D3
:
•
•
•
1,25(OH)2D3
23 (FGF 23)
FGF-23 –
32
,
,
257
30-60
.
FGF-23
,
(FGFR)
FGF-23
,
NaPi1
1,25(
25(
)D3
, FGF-23
)2D3
24,25(
)2D3
6
FGF 23 (2)
FGF 23
,
,
FGF 23
FGFR
FGF 23
FGF 23
.
,
1,25(
)2D3
FGF 23 (3)
FGF 23
FGF 23
,
Pi,
,
,
FGF 23
7
Klotho (1)
Klotho,
,
1997 . (
13
,
)
1014
(
)
NH2
ADAM17
980
ADAM10
Klotho,
,
,
FGF 23, Klotho
plexus
,
,
choroidal
Klotho
,
,
,
,
),
Klotho
Klotho (2)
Klotho
FGF 23
,
Klotho
FGF 23
FGF 23
(TRPV5)
(ROMK)
,
(TRPC6)
, Klotho
,
Klotho
,
Klotho
8
D. Sherrard (1993)
•
:
(
)
(
•
•
)
:
,
9
1
9
(CaR)
(VDR)
25(
1,25(OH)2D3
)D3
, FGF-23
(L.Quarles, 2012)
FGF-23,
,
1,25(
1,25(
)2D3
)2D3,
,
,
,
,
,
20
10
,
3
4
7
6
5
4
3
2
1
0
110-199
< 60
/1,73
200-299
300-399
400-499
461
2
500+
90
Johnson et al. National Kidney Foundation Spring Clinical Meeting,Chicago, IL April, 2006
21
VDR
:
3
4
CaSR
5
Tokumoto et al., Kidney Int., 2002
22
11
)
:
)
-
D
,
,
)
:
23
2
4
• 1,25(
•
)2D3
(OH)D3
• 22
-1,25(
, one alfa
)2D3
(OH)D2
19-
-1,25(
)2D2
24
12
)
,%
1- 84,%
(
Marianne Rix et al, Nephrol Dial Transplant (2004) 19: 870–876
D
n = 67,399
100
90
(%)
90
(%)
n = 16,483
100
80
80
70
70
60
60
50
50
40
40
30
3-
30
:
59%
20
51%
p<0.001
10
2-
20
:
73%
p=0.04
10
0
64%
0
0
5
10
15
20
25
30
35
0
40
(
5
10
15
20
25
30
35
40
)
Teng M et al., N Engl J Med 2003;349:446–56.
26
13
2)
(
,
24
48
Am Heart J 2012; 164: 902-909.e2.
27
II
(
40
100
20
0
VDR (-/-)
60
200
VDR (+/+)
80
300
VDR (-/-)
.)
400
100
*
*
120
.
500
II,
140
*
VDR (+/+)
600
0
VDR(+/+)
VDR(-/-)
Kong et al., ASN Meeting, 2005
28
14
,
CaSR
CaSR
2
9
,
CaSR
(
Ca2+.
)I
II
CaSR,
Ca2+,
III
,
,
(
)
CaSR
II
,
,
,
,
CaSR
29
3
[
100
)
300 - 499
1000
500 - 800
>800
80
(
1200
]
800
60
600
40
–65%*
–31%*
20
400
(
–49%*
200
)
=
: 150-300
0
0
-6
300 - 499
500 - 800
> 800
.
.3
.6
n = 275
n = 435
n = 606
n = 328
n = 483
n = 660
Ureña et al, Nephrol Dial Transplant 2009;24:2852-9.
. 12
.
12
30
15
100
90
80
70
60
%50
40
30
20
10
0
2,24
2704
74%
74%
,
0,58
Glen T. Schumock et al., Nephron Clin Pract 2011;117:c151–c159
3
2
INTIMA
MEDIA
90%
Mönckeberg)
60%
30%
:
20%
:
)
,
,
,
,
,
.
32
16
(
)
33
5
)
1
0
1
0.75
2
0.5
3
0.25
4
p<0.0001
N = 110
0
0
20
40
60
(
80
)
Blacher et al., Hypertension, 2001
34
17
3
5
Al
Ca
Mg
(
,
)
(Fosrenol)
(
435
235
+
)
35
3
6
18
3
7
Ca x
3,5
)
7
,
6,5
RenaGel
6
5,5
2,5
Ca x
5
2
Ca x P (
3
4,5
0
1 Pi 2
3
4
5
6
7
8
9
10 11 12
,
Ca x P
E. Slatopolsky et al., Kidney Int, 1999; v.55, p 299
3
8
80
75
70
60
50
40
141
52
37
30
20
10
0
0
0
1
Chertow GM et al., Kidney International 2002; 62:245-252
19
,
:
«
»
,
20