:

;
;
. MSc PhD

. &
, ...


2.400 mg

2 30 mg
24

Despopoulos, Color Atlas of Physiology 2003

ADA Positional Statement: Diabetes Care 2015

: 2,5mg/mmol
: 3,5
/

24/ 30 mg

20

30

mg/mmol

300 mg

200

>3g

5000

GFR (mL/min)

150

100

1000

50

200

20

0
5

10

15

20

(mg/24 h)

25

Strippoli et al. J Nephrol 2003;16:487499

25%
40-50%
, , , ,

, ,
, ,
,

S III:

28,8% (20-40%)

16% (11-40%)

( , , )

6,1% & 9,7%

40

5.1%

5-7%

Jones CA: Am J Kidney Dis 2002

 PREVEND:

(%)

16,4
11,5
6,6

Hillege, J Intern Med 20

 NEFRON

eGFR <60ml/min/1,73m2
2
(n=3.893)

20,1 %
4,1 %
3,2 %

7,3 %
12,4 %

1 2

eGFR <60ml/min/1,73m2

Thomas et.al., MJA, 185,140-144,20

LVH

CRP

LVH

vWf
QTc

CRP
, IL

 100

60

/
/
/
/

x 2,8

50

x 2,0

40
30

x 1,7

x 2,1
x 2,5

20
x 2,3

10
0

CHF*

AMI*

CVA/TIA*

PVD*

ASVD*

* CHF= , AMI= , CVA/TIA=

/ , PVD= ,
ASVD= . SVD AMI, CVD/TIA PVD. 1.
Foley RN, et al. J Am Soc Nephrol 2005;16:48995.

 :

(CV)
GFR

CV

( 100 )

40
35
30
25
20
15
10
5
0
60

4559

3044

1529

<15

GFR
CV
, ,
(mL/min)

1. Go AS, et al. N Engl J Med 2004;351:1296305.

m
m
H
16
0
>

27
0
>

A/
C

ra
tio

>

0,

65

m
m
ol
/L

m
g/
m

m
ol

N=2.085; 10

Arterioscler Thromb Vasc Biol. 1999;19(8):1992-1997.

PREVEND:

40.856

3
518

(.. 5
10 mg/L 10 20
mg/L) 1,29

Hazard
Ratio

Hillege: Circulation 2002

4
3
2
1
0

<140

140160

>160

(mmHg)

N = 2085; 10-year follow-up; prospective, open-ended, population-based cohort.

Borch-Johnsen K, et al. Arterioscler Thromb Vasc Biol. 1999;19:1992-1997.

, , , , .,
2,7 (1,56-4,70)
JACC, 151,18,1775-83 2008

:
2

(g/ml)
1.0

15 (n=328)
16-40 (n=88)

41-200 (n=62)

0.5

0.0
5

10

Schmitz et al. Diab Med 1988;5:12634

A: - <150
mg/L
1.
0
0.9

B: - 150300
mg/L
40

0.8

0.7
0.6
0.5
0

C
: p <0,001

(%)

&
2

p <0,001
30
20
10
0

0 10 20 30 40 50 60 70 80 90

C: - >300
mg/L

-,
Miettinen H et al. Stroke. 1996;27:20332039.

<140/90 mmHg

LDL
<100 mg/dl ( )
<70 mg/dl ( )

,

Weir MR. Clin J Am Soc Nephrol 2007

Ang I

Ang II

Brown MJ. Heart 2001;86:113120

0
25

50

73
75
100

Baseline > 1,5 mg/dl

4
%

mmHg

Collaborative Study Group:

Lewis EJ et al. N Engl J Med 1993;329:1456-1462.

 1
40

, ,
(%)

30
* p = 0,006

20

*
10

0
0

2
()

Lewis EJ et al. N Engl J Med 1993;329:1456-1462.

Mean albumin/creatinine ratio

MICRO-HOPE
3.0

Placebo

2.5
2.0

P=0,02

1.5

P=0.001

1.0
0.5
0

4.5

HOPE Study Investigators, Lancet 2000;355:253-59

Ang I

Ang II

ARB

Brown MJ. Heart 2001;86:113120

MARVAL

icroAlbuminuria Reduction
with VALsartan Study

80 mg
5 mg

24

140/80 mmHg

332 2

135/78 mmHg

22%
vs. 14,5%

126/76 mmHg

Viberti: Circulation 2002

RENAAL

:140/74 mmHg
142/74 mmHg placebo
p=0,59

% with event

30
20

L
0

P (+CT)
L (+CT)

762
751

12
689
692

762
751

50
% with event

% with event

Risk Reduction: 25%

p=0.006

10

0
P (+CT)
L (+CT)

20

10

30

Risk Reduction: 28%

p=0.002

24
Months

36

554
583

295
329

48

12

24
Months

36

48

715
714

610
625

347
375

42
69

40

Risk Reduction: 20%

p=0.010

30

20

10
0

36
52
P (+CT)
L (+CT)

12

24
Months

36

48

762
751

715
714

610
625

347
375

42
69

Brenner et al. NEJM 2001

Median Percent Change

RENAAL:

40
20

0
p=0,0001

-20

35%

-40
-60

P (+CT)
L (+CT)

12

24
Months

36

48

762
751

632
661

529
558

390
438

130
167
Brenner et al. NEJM 2001

IRMA 2:

18

16
24%
14

(%)

RRR=70%
P<0.001

RRR=39%

P=0.08

14.9

24%

12
9.7

10
8
6

34%
5.2

4
2
0

(n=201)

150 mg
(n=195)

300 mg
(n=194)

Parving H-H, et al. N Engl J Med 2001;345:870-878.

IRMA 2:

(%)

20

150 mg
300 mg

15
10
5
0
0

12
()

18

22

24

Parving H-H, et al. N Engl J Med 2001;345:870-878.

IRMA 2:

110

Placebo
150 mg 20
300 mg 10

108

112

Urinary
Albumin Excretion (%)

(mmHg)

106
104
102
100
98

12

18

24

()

*P<0,001 vs. placeb

-10
-20
-30
-40
-50

*
0

12

18

24

()

Parving, HH et al. NEJM 2001;345: 87

RENAAL: CV
(<30%)

RR 1.92
RR
2.7

De Zeeu: Circulation 2004

RENAAL:
(>30%)
CV
50%


18%
27%

De Zeeu: Circulation 2004

 1
-

DCCT: 1.441 1

( 39%) ( 54%)
The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977-86.

UKPDS:
HbA1c 0,9%
11 ,
( )
*Vs

(12 )

12%
16%
25%
29%
24%
33%

P value

0,029
0,052
0,0099
0,0031
0,046
<0,001
UKPDS Group. Lancet. 1998;352:837-853.

(%)

UKPDS 33:

-34 %
-67 %

-74 %
UKPDS Group (UKPDS 33). Lancet 1998;352:83753.



ADVANCE:
5 11.140
HbA1c :

6,5%

7,5%

:
65%
9%
30%

Percovic V et al., Kidney Int. 83 (3), Mar,

2013


: ADVANCE
4,3 (N=11.140)

150
125
100

18%

100

33%*

96

81

75
50

20%

120

Placebo
+

*P=0,005 placebo
Zoungas S, et al. Diabetes Care 2009;32:206874.

 GREACE:

, (n=703)
, (n=97)
, (n=783)

15
10
5
0
-5
-10

CrCl (%)

CrCl (%)

(CHD) : 12% 24,5%

(RR 0,49, P<0,0001)
5%
(HR 0,84, P=0,003)
10%
SC Q1 (n=200)
SC Q3 (n=200)

(HR
0,73,
P<0,001)
UC Q1 (n=200)
UC Q3 (n=200)
, (n=17)

6 12 18 24 30 36 42 48

SC Q2 (n=200)
UC Q2 (n=200)

SC Q4 (n=200)
UC Q4 (n=200)

20
15
10
5
0
-5
-10

6 12 18 24 30 36 42 48

(SC 4)

* (P<0,05) , CrCl =
,
Q = , SC = , UC =

Athyros VG, et al. Curr Med Res Opin 2002;4:2208.

Athyros VG, et al. J Clin Pathol 2004;57:72834.


()
GFR (E)
:
()

ADA 2015
Cockroft-Gault
Ccr(ml/min)=

(140-) x . x (0,85 . )
72 x Cr

MDRD
GFR(ml/min/1.73m2)=

186 x Cr (-1.154) x

(0.203)

x (0.72 )




, 2


,

:
HbA1c <7%

(RAS):
/ ARBs

Bowman

:
LDL <100 mg/dL,
<70 mg/dL ( )

<130/80
mmHg

( II)
II

ARB =
1. Perkins BA, et al. N Engl J Med 2003;348:228593. 2. Gerstein HC, et al. JAMA 2001;286:4216. 3. Jude AE et
al. QJM 2002;95:371377;
4. National Kidney Foundation. Am J Kidney Dis. 2007;49(Suppl 2):S4261. 5. American Diabetes Association.