study on hemodynamic index of kidney arteries and glomerular filtration rate in essential hypertension patients

MINISTRY OF EDUCATION AND TRANING MINISTRY OF NATIONAL DEFENCEVIETNAM MILITARY MEDICAL UNIVERSITY NGUYỄN VĨNH HƯNG STUDY ON HEMODYNAMIC INDEX OF KIDNEY ARTERIES AND GLOMERULAR FILTRATIO

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 year 2014

Find thesis in

1 National library

2 Vietnam military medical university

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.

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

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 non- controlled 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

Male (n=165) 59,1 ± 10,2 60,6 ± 9,7 >0,05

Female (n=168) 59,3 ± 9,3 59,3 ± 9,5 >0,05

p >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 < 0,0551-60(n=55) 2,29 ± 0,71 1,27 ± 0,17 < 0,0561-70(n=62) 2,24 ± 0,54 1,26 ± 0,17 < 0,05

>70(n=37) 1,75 ± 0,40 1,27 ± 0,17 < 0,05all 2,26 ± 0,72 1,25 ± 0,16 < 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

Increased ( >1,57 mg/l) n (%)

Normal (0,93 - 1,57mg/l) n

(%)

Decreased (<0,93 mg/l) n (%)

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

Gender

Microalbuminuria MAU (+) n (%) Concentration (mg/24h) (

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) Microalbumin (+)

>5 (n=91) 18 (31,6) 18 (12,9)

Comment: microalbumin (+) increased by time and diferent significalty p<0,05

compared microalbumin negative.

Table 3.7: microalbuminuria by stage of HTA

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

X ± SD ) (ml/min)

p HTA (n=197) Control (n=136)

40-50(1) 86,3 ± 8,5 103,9 ± 11,0 <0,05

51-60(2)

(nb=55)(nc=42) 81,6 ± 9,3 95,7 ± 10,2 <0,0561-70(3)

(nb=62)(nc=44) 72,4 ± 6,3 85,3 ± 8,6 <0,05

> 70(4)

(nb=37)(nc=30) 73,2 ± 6,5 82,4 ± 9,1 <0,05All

(nb=197)(nc=136) 78,2 ± 8,8 90,6 ± 9,5 <0,05

p 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

Age GFR ( X ± SD ) (ml/min)

p stage I (n=91) stage II (n=106)

Comment: GFR diferent significalty p<0,05 betwen stage I and II

Table 3.10: GFR (ml/min) by time of HTA

Time (year) GFR ( X ± SD ) (ml/min)

All (n=197) 78,2 ± 8,8

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

Table 3.12: BFV by time HTA

51-60 (2)

(n=55) 922,6 ± 172,5 887,3 ± 39,7 <0,05

909,8 ±139,9

Comment: BFV in HTA sage II lower than HTA stage I significalty.

Table 3.13: Speed of blood flow (cm/s) by position

Index Entry of artery Hile Parenchyme p

Index Entry of artery Hile Parenchyme

RI

( X ± SD)

Right 0,63 ± 0,08 0,59 ± 0,08 0,59 ± 0,09Left 0,64 ± 0,08 0,62 ± 0,09 0,59 ± 0,09All 0,63 ± 0,06 0,61 ± 0,07 0,59 ± 0,08

PI

( X ± SD)

Right 1,00 ± 0,15 0,92 ± 0,18 0,98 ± 0,18Left 1,04 ± 0,18 0,95 ± 0,12 0,97 ± 0,15All 1,02 ± 0,14 0,94 ± 0,11 0,97 ± 0,14

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

Age

BFV ( X ± SD) (ml/phút)

p Mcroalbumin (+)

(n=57)

Microalbumin (-) (n=140)

40-50 (n=43) 895,5 ± 11,8 990,5 ± 176,5 >0,0551-60 (n=55) 866,3 ± 54,7 919,4 ± 151,3 >0,0561-70 (n=62) 885,6 ± 57,2 895,6 ± 24,3 >0,05

> 70 (n=37) 895,6 ± 33,9 892,7 ± 27,6 >0,05All (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

Table 3.17: Relationship of BFV with another parameters

Mean blood pressure -0,126 (Spearman) 0,078

Comment: BFV had relationship with GFR (r = 0,279 và p<0,05) and RI, PI but not

(n=57)

Microalbumin (-) (n=140)

II (n=106) 73,1 ± 6,8 77,4 ± 8,1 >0,05All (n=197) 74,4 ± 7,1 79,7 ± 8,5 >0,05

PI ( X ± SD) 0,89 ± 0,18 0,94 ± 0,18 >0,05Parenchy

m

RI ( X ± SD) 0,60 ±0,08 0,58 ±0,09 >0,05

PI ( X ± SD) 1,01 ±0,22 0,97 ±0,16 >0,05

Comment: group microalbumin (+) have RI, PI no different with microalbumin (-).

Table 3.21: Correlation of RI, PI with BP and PCR

4.1 Characteristics of age

Our study shows that hypertension increases with age: under 50 years group was21.8%, the age group 50-60 is 27.9%, the group of 61-70 years was 31.5%; 70-year-old group was 18.8% The results of our study are similar to the study by Pham ThiKim Lan (2002), Dong Van Thanh (2011) According to the JNC VII, hypertensivekidney disease increases with age Most cases are diagnosed with kidney disease arehypertension, the middle-aged and elderly people These groups are very difficult todistinguish 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 Iaccounted for 46.2% 106 patients with stage II, 53.8% The difference in thisproportion significantly p <0.05 Most patients with hypertension in this study wasmild to moderate In this study, no patients with stage III hypertension According tothe classification of hypertension by the world health organization, hypertensivepatients 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 withproteinuria were broadly positive, the patient did not see any blood pressure over 2organ damage

4.3 Change the concentration of blood rennin

Important mechanism between renal damage and hypertension role ofaldosterone-renin-angiotensin system We examined blood parameters renin to learnthis association In the present study we found that the concentration of renin inhypertension 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 reninconcentration decreases with age have statistically significant p <0.05 While in thecontrol group relative renin concentration constant Thus the concentration in theblood renin hypertension decreased with age, while those without hypertension reninlevels stable Fink H.A 2012 study of renal lesions seen in patients with chronickidney disease, the angiotensin converting enzyme inhibitors and AT1 receptor

inhibition reduces the risk of end-stage renal failure, reduced mortality risk ofmyocardial infarction and sudden stroke, thereby confirming the role of the renin-angiotensin 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 Thismay indicate that the glomerular filtration rate depends on the internal blood pressureand glomerular affected by systemic blood pressure, higher blood pressure, increasedglomerular filtration rate decreases Initial blood pressure makes the blood flow tothe kidneys increases and increased glomerular filtration rate But then over time theresponse 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 cansee 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 severelyimpaired control of blood pressure treatment and maintain kidney function verydifficult This study shows that the achieved blood pressure control targets to reduceCKD patients as well as blocking lesions in other organ

Table 4.1 Change glomerular filtration rate in patients with hypertension.

4.5 Change renal blood flow

In people with primary hypertension renal blood flow is 916,5ml / min inhealthy blood flow to the kidneys is 1044.2 ml / min The difference between the twogroups is statistically significant When hypertensive renal blood flow will decrease,reducing the operational capability of the kidneys and renal nutrition Externalcauses pressure problems are caused by progressive renal fibrosis in patients withhypertension in a long time Analysis by age and stage of hypertension and saw theblood flow to the kidneys in people with stage I hypertension greater than those withhypertension stage II This can be explained in the early stages when the kidneys arenot damaged, more fibrosis, renal blood flow depends mainly on the blood pressurehigh blood pressure, the blood flow to the kidney Over time as renal lesions of therenal response to blood pressure numbers are not as original and renal blood flow arenot dependent on blood pressure numbers more

Table 4.2 Renal blood flow (ml/min) in patients with hypertension

4.6 Impedance change index (RI) and pulse index (PI)

Research on the index and renal vascular resistance index of renal artery RI dam,

PI found no differences were statistically significant between RI and PI indices in theright kidney and left kidney, between the disease and the control group We analyzethe impedance index RI phased hypertension and found that RI and PI increased in