MINISTRY OF EDUCATION AND TRANING MINISTRY OF NATIONAL DEFENCE
VIETNAM MILITARY MEDICAL UNIVERSITY
NGUYỄN VĨNH HƯNG
STUDY ON HEMODYNAMIC INDEX OF KIDNEY ARTERIES
AND GLOMERULAR FILTRATION RATE
IN ESSENTIAL HYPERTENSION PATIENTS
Specialist: Nephrology-Urology
Code: 62.72.01.46
Epitomize of PhD thesis
Hanoi - 2014
Research completed in:
VIETNAM MILITARY MEDICAL UNIVERSITY
Supervisor I: AssProf. PhD HA HOANG KIEM
Supervisor I: AssProf. PhD DINH THI KIM DUNG
Scientific reviewer I: Ass.Prof TRAN VAN CHAT
Scientific reviewer II: Ass.Prof DOAN VAN DE
Scientific reviewer III: AssProf. PhD NGUYEN VAN QUYNH
Thesis will be presented in university examiner assembly
In Vietnam military medical university
At
hour
min, day
month
Find thesis in
1. National library
2. Vietnam military medical university
year 2014
INTRODUCTION
Hypertension (HTA) is cause and consequences of CKD. Renal
failure is severe of HTA and affects quality of life’s patients and is the
heavy burnde of social. USRDS 2005 showed 27% FSRD caused by
HTA, HTA is 2nd caused less than diabetes 51%. WHO warned HTA in
Vietnam will be most important cause of ESRD in near future.
HTA lead increasing of blood flow of kidney and intragromerular
pressure increase. Belong the time, normal structure of gromeruli will be
destroyed, sclerosis and kidney function decreased and the end ESRD.
HTA destroyed all kinds of kiney arteries by the longtime hype
pressure. This procedure is dangerous because it hell is “silent”. Signes
appearred late, when loss kidney function.
Doppler ultrasound is non-invasive intervention for diagnose
follow up kidney arteries disorder. This technique help find out early
injury caused by HTA. There are many research about disease caused by
HTA. Therefore need more research in hemodynamic kidney arteries
and gromerular filtration rate. Information received help diagnose early,
prevent kidney complication of HTA.
OBJECTIF
1. Study on hemodynamic index (HI)(speed of blood flow, blood flow
volume, resistance index, pulsasitive index); Plasma renin concentration
(PCR) and gromerular fitration rate (GFR) in essential HTA with
negative macroalbuminuria.
2. Relationship of blood flow volume (FV) of kidney arteries, GFR with
PRC, and anothers hemodynamics index.
NEWCONTRIBUTION OF THESIS
- Result received reconfirms HI of kidney arteries, GFR depend on
HTA situation: Stage of HTA, time of HTA.
- Warning
clinical
physics
evaluate
completely,
systematic,
chronology HI, GFR, PCR in essential patients to prevent renal
injuries.
CONTENT OF THESIS
Thesis have 124 pages: Introduction 2 pages, Chapter 1:
Background
24 pages, Chapter 2: Subjects and method 15 pages,
Chapter 3: Result 33 pages, Chapter 4: Discusion 29 pages.
Thesis has 44 tables, 3 schemas, 3 images. References 162: in
Vietnamese 26 and 146 in English.
Chapter 1
BACKGROUND
1.1.
Kidney injuries caused by HTA
Early, changing of function passed in the longtime recurred if
right treated. Later, sclerosis accelerated and dimension of kidney
decreases cause ERSD.
GFR in early time maintain with low FV (flow volume) but later
GFR decreased and ESRD at the end.
All of kidney arteries injured but mostly in afferent arteries. The
character of histological injuries’ is intimae artery and endothelia
destruction sclerosis, necroses all of the arteries.
1.2. GFR disorder in HTA
Theory, changing of pressure lead changing function, later
structure destroyed, belong the time abnormal struction decreases
function. Actually, most of CKD hypertensions aren’t treated. In early
time of HTA, GFR in normal ranger or increase lightly. Late, when MAU
appeared, GFR in normal range. If patient aren’t under good HTA
controlled; Microalbumin or clinical protein in uria appeared, GFR
decrease significally, clinical signs of renal failure more severe.
GFR loss in HTA patient caused by renal auto regulation system
dysfunction. Auto regulation contraction of afferent arteries and refection
tubulo-glomerular system disordes. HTA chonic patient from epithelial
dysfunction and structural arteries destroyed. Intragromerular pressure
decreased with blood pressure higher than 80mmHg and increase with BP
higher than 160mmHg.
1.1 . Renal artery interventional method
-
Direct method:
+ Ultrasound color Doppler
+ Digital angiography
+ MRI
-
Indirect
+ Intravenous urography, image nuclear
+ Biochemical test
1.2 . Researches hemodynamic index and GFR in HTA patients in
Vietnam and global.
MDRD research showed CKD patient have slower decreased of GFR if
volume controlled HTA compared non-controlled. Resumed of 9 clinical
researches on the changing of GFR in HTA patients: CKD patient noncontrolled HTA (more than 140/90mmHg) – GFR decreased 12ml/min/year.
Inversing well control HTA (<130/80mmHg) GFR decreased 2ml/min/year.
(similar normal subject).
Peterson and al conclude RI and PI of renal arteries have closed
relationship with another HI and GFR.
In Vietnam, Tran Bui (2002) evaluated HI of renal arteries by Doppler
ultrasound. 35 normal subject competed 35 hypertensive’s patients with age
30-79. Blood follow (BF) in subject is 842ml/min. (HTA) (decreased
significality patients 262ml/min =24%.
Huynh Van Nhuan 2005 studied on 36 CKD compared 22 normal
showed RI and PI increased significality (0,79 compared 0,665) 2,13
compared 1,22.
Chapter 2
SUBJECT AND METHOD
2.1. Subject:
- 333 peoples divide 2 groups: 136 normal and 197 HTA patients with age
40-90; among them 91 male and 106 female.
- Patients followed up in E hospital with essential HTA diagnosed,
proteinuria negative, GFR > 60ml/min.
2.2 Method:
- Perspective, controlled, description.
- Time of study: Jan/09 – Jan/2012
- Location: E hospital
2.2.2 Steps of study
Step 1: Chose study subject
Clinical consultation; BP measured, urin test 10 index, ultrasound kidney
and urology system.
Step 2:
- Measured BP; GFR test, MAU test, ultrasound Doppler kidney arteries.
- Collect research parameters recorded, and stopped all of HTA
treatments possible
Step 3: Analyze parameters collected by mathematical statistic SPSS 10.0
- Mean, SD
- Relationship under
- Compare mean, %
- Result statistical signification with p<0,05
- Result presented schema, table, image
Chapter 3
RESULT OF RESEARCH
3.1 Character of subjects
Table 3.1: Mean age
Gender
Male (n=165)
Age (
X
± SD) (year)
HTA (n = 197)
Control (n = 136)
59,1 ± 10,2
60,6 ± 9,7
p
>0,05
Female (n=168)
59,3 ± 9,3
59,3 ± 9,5
p
>0,05
>0,05
all
59,2 ± 9,7
60,0 ± 9,6
>0,05
>0,05
Comment: mean age of HTA patients isn’t different normal subject with
p≥0,05 the same for gender
Table 3.2. Stage of HTA
Age
stage I n (%)
Stage II n (%)
p
all n (%)
40-50
38 (88,4)
5 (10,6)
< 0,05
43 (21,8)
51-60
35 (63,6)
20 (36,4)
< 0,05
55 (27,9)
61-70
16 (25,8)
46 (74,2)
< 0,05
62 (31,5)
> 70
2 (5,4)
35 (94,6)
< 0,05
37 (18,8)
All
91(46,2)
106(53,8)
< 0,05
197 (100)
Comment: percentage of HTA stage I higher than stage II sihnificaltly. No one
stageIII
3.2.
Plasma concentration of renin (mg/l)
Table 3.3: PCR (mg/l)by age
Age
Renin (
X
± SD) (mg/l)
p
HTA(n=197)
Control (n=136)
40-50(n=43)
2,70± 0,86
1,16 ± 0,11
< 0,05
51-60(n=55)
2,29 ± 0,71
1,27 ± 0,17
< 0,05
61-70(n=62)
2,24 ± 0,54
1,26 ± 0,17
< 0,05
>70(n=37)
1,75 ± 0,40
1,27 ± 0,17
< 0,05
all
2,26 ± 0,72
1,25 ± 0,16
< 0,05
p
< 0,05
>0,05
Comment: PRC mean in HTA group higher than normal significaltly p<0,05.
More young more different in normal group PRC don’t change with age but in
HTA group PRC decreased with age.
Table 3.4: Percentage increased-decreased PRC
Age
Increased
Normal
( >1,57 mg/l) n
(0,93 - 1,57mg/l) n
(%)
34 (23,6)
39 (27,1)
48 (33,3)
23 (16,0)
144 (73,1)
40-50(n=43)
51-60(n=55)
61-70(n=62)
>70(n=37)
All
Decreased
(%)
9 (17,0)
16(30,2)
14 (26,4)
14 (26,4)
53 26,9)
(<0,93 mg/l) n (%)
0
0
0
0
0
Comment: We defined normal range level of PRC 0,93-1,57 from table3.6. In
research 144 HTA PRC increased 73,1% and no one decreased different
significantly.
3.3. Microalbuminuria
Table 3.5: Microalbuminuria
Microalbuminuria
Gender
MAU (+) n (%)
Concentration (mg/24h) (
X
± SD)
Male (n=91)
32 (56,1)
43,9 ± 64,3
Female (n=106)
25 (43,9)
31,5 ± 60,9
p
< 0,05
>0,05
All (n=197)
57 (28,9)
37,9 ± 62,9
Comment: 57 patients with microalbuminuria (+) is 28,9%. among microalbumin
(+), male 56,1% female is 43,9%, diferent significalty p<0,05.
Table 3.6: microalbuminuria by time of HTA
Time (year)
<1 (n=39)
Microalbumin (+)
Microalbumin (-)
n (%)
n (%)
5 (8,8)
13 (9,3)
1-5 (n=67)
34 (59,6)
109 (77,8)
>5 (n=91)
18 (31,6)
18 (12,9)
p
<0,05
<0,05
All
57 (28,9)
140 (71,1)
Comment: microalbumin (+) increased by time and diferent significalty p<0,05
compared microalbumin negative.
Table 3.7: microalbuminuria by stage of HTA
Stage
Microalbumin (+) n
Microalbumin (-) n
(%)
(%)
I (n=91)
13 (22,8)
78 (55,7)
<0,05
II (n=106)
44 (77,2)
62 (44,3)
<0,05
p
<0,05
>0,05
OR
p
4,258
Comment: Microalbuminuria
(+) increased by stage HTA significalty p<0,05.
Patients HTA stage II risk microalbumin niệu (+) higher 4,258 time stage I. diferent
significalty p<0,05 microalbumin (+) and microalbumin niệu (-) by stage.
3.4. Gromerular filtration rate (GFR)
Table 3.8: GFR (ml/min) by age
Age
GFR (
HTA (n=197)
X
± SD ) (ml/min)
Control (n=136)
p
40-50(1)
(nb=43)(nc=20)
51-60(2)
(nb=55)(nc=42)
61-70(3)
(nb=62)(nc=44)
> 70(4)
(nb=37)(nc=30)
All
(nb=197)(nc=136)
p
86,3 ± 8,5
103,9 ± 11,0
<0,05
81,6 ± 9,3
95,7 ± 10,2
<0,05
72,4 ± 6,3
85,3 ± 8,6
<0,05
73,2 ± 6,5
82,4 ± 9,1
<0,05
78,2 ± 8,8
90,6 ± 9,5
<0,05
p¹ p² <0,05
p¹ p²<0,05
(pº: p2/1; p¹: p3/1; p²: p4/1; p³: p4/2) (nb: HTA; nc: Control).
Comment: GFR decreased by age in two group significalty.
Table 3.9: GFR (ml/min) by HTA stage
X
GFR (
± SD ) (ml/min)
stage I (n=91)
stage II (n=106)
87,5 ± 8,7
86,6 ± 7,2
80,7 ± 9,3
83,1 ± 9,3
77,1± 7,5
75,3± 7,1
76,2 ± 7,9
73,0 ± 6,3
81,1 ± 8,6
75,6 ± 7,9
Age
40-50 (n=43)
51-60 (n=55)
61-70 (n=62)
> 70 (n=37)
All (n=197)
p
>0,05
>0,05
>0,05
>0,05
<0,05
Comment: GFR diferent significalty p<0,05 betwen stage I and II.
Table 3.10: GFR (ml/min) by time of HTA
Time (year)
<1 (n=39)
GFR (
X
± SD ) (ml/min)
71,5 ± 23,9
1-5 (n=67)
78,1 ± 19,3
>5 (n=91)
81,8 ± 18,9
All (n=197)
78,2 ± 8,8
p
> 0,05
Comment: by time HTA, GFR seem decreased but not significalty.
3.5.
Hemodynamic index of kidney arteries
Table 3.11: Blood flow volume (ml/min) right and left by age
Age
40-50
51-60
61-70
> 70
All
BFV (
X
± SD) (ml/min)
Right
Left
p
all
HTA
476,6 ± 88,9
505,1 ± 82,1
>0,05
981,6 ± 170,2
Control
597,6 ± 64,3
605,9 ± 63,8
>0,05
1203,5 ± 127,7
p
<0,05
<0,05
HTA
443,8 ± 66,0
473,2± 67,7
>0,05
909,8 ± 139,9
Control
546,1 ± 94,1
556,2 ± 89,1
>0,05
1102,3 ± 182,8
p
<0,05
<0,05
HTA
429,7 ± 20,0
461,2 ± 26,4
>0,05
890,9 ± 42,9
Control
500,9 ± 151,2
502,6 ± 150,9
>0,05
1003,5 ± 301,6
p
<0,05
>0,05
HTA
434,6 ± 13,0
459,2 ± 21,1
>0,05
893,8 ± 29,7
Control
454,2 ± 147,4
461,9 ± 146,9
>0,05
916,1 ± 293,8
p
>0,05
>0,05
HTA
444,8 ± 58,0
473,7 ± 57,5
>0,05
916,5 ± 116,6
Control
518,8 ± 131,9
525,4 ± 131,2
>0,05
1044,2 ± 262,6
p
<0,05
<0,05
Comment: BFV no different betwen kidney right and left.
<0,05
<0,05
<0,05
>0,05
<0,05
Table 3.12: BFV by time HTA
BFV (
Age
X
± SD) (ml/min)
Stgae I (n=91)
Stage II (n=106)
p
990,3 ± 179,3
915,7 ± 27,8
<0,05
922,6 ± 172,5
887,3 ± 39,7
<0,05
898,7 ± 27,1
888,2 ± 47,1
>0,05
890,9 ± 42,9
> 70 (4)(n=37)
880,7 ± 39,9
894,5 ± 29,6
>0,05
893,8 ± 29,7
All (n=197)
945,8 ± 161,6
891,4 ± 39,9
<0,05
40-50 (1)
(n=43)
51-60 (2)
(n=55)
61-70 (3)
(n=62)
All
981,6 ±
170,2
909,8 ±
139,9
916,5 ±
116,6
Comment: BFV in HTA sage II lower than HTA stage I significalty.
Table 3.13: Speed of blood flow (cm/s) by position
Index
Vs (
Vd (
Vm (
X
X
X
± SD) (cm/s)
± SD) (cm/s)
± SD) (cm/s)
Entry of artery
Hile
Parenchyme
p
98,0 ± 7,2
51,7 ± 6,0
32,3 ± 4,9
<0,05
33,9 ± 4,9
22,3 ± 4,9
13,5 ± 4,7
<0,05
50,8 ± 5,0
35,3 ± 4,9
20,4 ± 4,9
<0,05
Comment: BF different in 3 position, decreased from out to centre.
Table 3.14: RI, PI
Index
Entry of artery
Hile
Parenchyme
Right
0,63 ± 0,08
0,59 ± 0,08
0,59 ± 0,09
Left
0,64 ± 0,08
0,62 ± 0,09
0,59 ± 0,09
All
0,63 ± 0,06
0,61 ± 0,07
0,59 ± 0,08
Right
1,00 ± 0,15
0,92 ± 0,18
0,98 ± 0,18
Left
1,04 ± 0,18
0,95 ± 0,12
0,97 ± 0,15
All
1,02 ± 0,14
0,94 ± 0,11
0,97 ± 0,14
RI
(
X
± SD)
PI
(
X
± SD)
Comment: RI , PI decreased from outside to parenchym. No different betwen right
and left.
3.6. Relationship of BFV, GFR, PCR
3.6.1. Parameters of entry position
Table 3.15: BFV (ml/min) by microalbuminuria
BFV (
Age
X
± SD) (ml/phút)
p
Mcroalbumin (+)
Microalbumin (-)
(n=57)
(n=140)
40-50 (n=43)
895,5 ± 11,8
990,5 ± 176,5
>0,05
51-60 (n=55)
866,3 ± 54,7
919,4 ± 151,3
>0,05
61-70 (n=62)
885,6 ± 57,2
895,6 ± 24,3
>0,05
> 70 (n=37)
895,6 ± 33,9
892,7 ± 27,6
>0,05
All (n=197)
885,4 ± 49,9
929,2 ± 132,6
>0,05
Comment: In group microalbuminuria (+) BFV seem decreased compared group
microalbumin (-) but not significalty.
Table 3.16. Relationship of BFV with speed flow and artery surface
Right
Left
Parameters
HTA
control
HTA
control
Vm (cm/s)
53,3
53,3
48,3
48,7
BFV (ml/min)
444,8
518,8
473,7
525,4
Surface (cm2)
0,14
0,16
0,16
0,18
Comment: BFV and surface of kidnet arteries decreased in group HTA significalty
but not Vm.
Table 3.17: Relationship of BFV with another parameters
Parameters
GFR
Renin (PCR)
RI
PI
Mean blood pressure
r
0,279 (Pearson)
0,076 (Spearman)
-0,136 (Pearson)
-0,150 (Pearson)
-0,126 (Spearman)
p
<0,05
0,290
<0,05
<0.05
0,078
Comment: BFV had relationship with GFR (r = 0,279 và p<0,05) and RI, PI but not
with PCR.
3.6.2. GFR Correlation with another parameters
Bảng 3.18: GFR (ml/min) by Microalbuminuria
GFR (
Stage HTA
X
± SD) (ml/min)
p
Microalbumin (+)
Microalbumin (-)
(n=57)
(n=140)
I (n=91)
78,8 ± 8,0
81,5 ± 9,3
>0,05
II (n=106)
73,1 ± 6,8
77,4 ± 8,1
>0,05
All (n=197)
74,4 ± 7,1
79,7 ± 8,5
>0,05
p
>0,05
>0,05
Comment: GFR in microalbumin (+) lower than group (-) but not significalty
p>0,05.
Bảng 3.19: Correlation of GFR with another parameters
Parameters
r
p
BP systolic
-0,096 (Pearson)
0,177
PCR
0,033(Spearman)
0,643
Vm
0,174 (Pearson)
0,014
RI
-0,300 (Pearson)
<0,001
PI
-0,127 (Pearson)
0,076
Comment: GFR had no collerated with BPS, PCR, PI but collerated with Vm and RI.
3.6.3. Correlation of RI and PI
Bảng 3.20: RI, PI by microalbuminuria
RI-PI
Entry
RI (
PI (
Hile
RI (
PI (
Parenchy
m
RI (
PI (
X
X
X
X
X
X
± SD)
± SD)
± SD)
± SD)
± SD)
± SD)
Microalbumin (+)
Microalbumin (-)
(n=57)
(n=140)
0,66 ± 0,08
0,61 ± 0,07
1,02 ± 0,19
0,99 ± 0,13
0,60 ± 0,09
0,59 ± 0,07
0,89 ± 0,18
0,94 ± 0,18
0,60 ±0,08
0,58 ±0,09
1,01 ±0,22
0,97 ±0,16
p
<0,05
>0,05
>0,05
>0,05
>0,05
>0,05
Comment: group microalbumin (+) have RI, PI no different with microalbumin (-).
Table 3.21: Correlation of RI, PI with BP and PCR
RI
PI
r
p
r
p
Mean BP
-0,032
0,652
0,072
0,317
BP systolic
0,096
0,179
0,059
0,410
BP diastolic
-0,039
0,586
0,056
0,433
Renin PCR
-0,168
0,019
-0,018
0,797
Comment: RI , PI had no related with BP and PCR
Chapter 4.
DISCUSSION
4.1. Characteristics of age
Our study shows that hypertension increases with age: under 50 years group was
21.8%, the age group 50-60 is 27.9%, the group of 61-70 years was 31.5%; 70-yearold group was 18.8%. The results of our study are similar to the study by Pham Thi
Kim Lan (2002), Dong Van Thanh (2011). According to the JNC VII, hypertensive
kidney disease increases with age. Most cases are diagnosed with kidney disease are
hypertension, the middle-aged and elderly people. These groups are very difficult to
distinguish the vascular damage due to age or due to hypertension.
4.2. Blood pressure
Analysis by stage of hypertension we found: There are 91 patients with stage I
accounted for 46.2%. 106 patients with stage II, 53.8%. The difference in this
proportion significantly p <0.05. Most patients with hypertension in this study was
mild to moderate. In this study, no patients with stage III hypertension. According to
the classification of hypertension by the world health organization, hypertensive
patients with stage III when there are more than 2 target organ damage. Meanwhile,
the agency is soon hurt the eyes and kidneys. When excluding patients with
proteinuria were broadly positive, the patient did not see any blood pressure over 2
organ damage.
4.3. Change the concentration of blood rennin
Important mechanism between renal damage and hypertension role of
aldosterone-renin-angiotensin system. We examined blood parameters renin to learn
this association. In the present study we found that the concentration of renin in
hypertension 197 (2.26 mg / l) significantly greater than the concentration of renin in
136 people in the control group (1,25mg / l). In the subgroup of patients renin
concentration decreases with age have statistically significant p <0.05. While in the
control group relative renin concentration constant. Thus the concentration in the
blood renin hypertension decreased with age, while those without hypertension renin
levels stable. Fink H.A. 2012 study of renal lesions seen in patients with chronic
kidney disease, the angiotensin converting enzyme inhibitors and AT1 receptor
inhibition reduces the risk of end-stage renal failure, reduced mortality risk of
myocardial infarction and sudden stroke, thereby confirming the role of the reninangiotensin system-aldosterone in target organ damage in hypertensive patients.
4.4. Change in glomerular filtration rate
Glomerular filtration rate decreases with increasing blood pressure stage. This
may indicate that the glomerular filtration rate depends on the internal blood
pressure and glomerular affected by systemic blood pressure, higher blood pressure,
increased glomerular filtration rate decreases. Initial blood pressure makes the blood
flow to the kidneys increases and increased glomerular filtration rate. But then over
time the response of the kidney is no longer as in the first phase and to a certain time
point, the glomerular filtration rate will decrease rather than increase. Through
research can see clearly the relative influence of blood pressure on glomerular
filtration rate.
Author Puttinger H. 2003 study in Austria found that hypertensive renal disease
is the main cause of end-stage renal failure. When kidney function is severely
impaired control of blood pressure treatment and maintain kidney function very
difficult. This study shows that the achieved blood pressure control targets to reduce
CKD patients as well as blocking lesions in other organ.
Table 4.1. Change glomerular filtration rate in patients with hypertension.
Author
GFR(ml/min/1,73m2)
We
78,2
I-SEARCH Việt Nam
65,8
I-SEARCH global
87,9
London G.M.
73
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