Nghiên cứu nồng độ beta2 microglobulin máu ở bệnh nhân suy thận mạn tính lọc máu chu kỳ (tt e) - Pdf 23

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FOREWORDS
1. The necessity of the topic
Chronic renal failure is a clinical and biochemical syndrome
progresses to chronic over several years, it is a result of fibrosis of
nephrons causing gradually decreasing glomerular filtration rate
(GFR) leading to increasing blood non-protein nitrogen likes urea,
creatinine. When the GFR < 10 mL/min, patients require kidney
replacement by dialysis or kidney transplant.
The patients with chronic renal failure make up a very large
proportion of the population, due to various causes, such as treament
difficult or expensive. Currently, there are 3 treatment methods for
end-stage renal failure:hemodialysis, peritoneal dialysis, kidney
transplant.According to statistics in 2012, there were 3,010,000 people
worldwide had been treated by kindney replacement method, increased
7% each year. Among these patients, there were about 2,358,000
people were treated by hemodialysis and peritoneal dialysis. 652,000
people were transplanted kidneys. In maintence hemodialysis patients,
when their life are prolonged, there is an increasing rate of
cardiovascular, neurological and musculoskeletal complications
leading to reduce life quality ; there are many causes of these
complications, the top cause is the dialysis method can not efficiently
filtrate some substances in serum, in particularly, substances with high
and average molecular weights. A representative is beta2-
microglobulin (β2M). When dialysis method does not have enough
effects, β2Mdeposites into some organs like skeletal system causing
pain, movement limitation, bone fractures ; into cardiovascular system
and digestive system causing other complications and leading to
increase the rate of hospitalized patients or deaths.
In Vietnam, there are some studies on blood β2M concentrations
in patients with renal failure on dialysis or not to assess the efficacy of

1.1. Summary on chronic renal failure
Chronic renal failure is the final result of chronic renal - urinary
diseases causing decreasing ability of the kidney corresponding to the
nephrons of the kidney that have been damaged and irreversibly lost
function.
There are many causes of chronic renal failure, the most common
causes are glomerular diseases, renal tubulo-interstitial diseases, renal
vascular disease, congenital and genetic diseases…
1.2. Clinical expressions and laboratory data of chronic renal
failure
Kidney is the organ holding several essential roles like endocrine,
exocrines and regulatory roles then when the kidney is damaged, many
other organs in our body will be affected.
Renal failure is divided into 5 stages, because the disease progress
slowly then it is often diagnosed at later stages leading to difficult in
treatment.
To diagnose renal failure ta the realy stage, the most important
thing is based on its sub-clinical expressions… In treatment of renal
failure, beside cause treatment, the main treatment approach is
reservation treatment because damaged nephrons are unable to revocer
when they are damaged and become fibrosis.
1.3. Method for treatment of the end-stage renal failure patients
When the GFR< 10mL/min, the patient must be treated by kidney
replacement. Currently, there are 3 primary treatment methods as
follows:
- Kidney transplantation: accounted about 15%. This is the
optimal alternative treatment method but the source of kidneys is rare.
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- Peritoneal dialysis : accounted about 16%, done at home, the
patient does not depend on the hospital and medical professionals but

Serumβ2M concentration increases depending on the reduction of
GFR. In patient on hemodialysis, the serumβ2M concentration can
increase> 30 folds as compared to healthy people. β2M increasing
leading to its deposition in some organs of the body causing Amylose
complication, in particularly in patient with more than 5 years
experiencing hemodialysis leading reduced life quality of the patient.
1.6. Studies on β2M in patients with renal failure
Abroad: there have been many studies on β2M in patients with renal
failure, patients on hemodialysis on pathophysiological mechanisms,
treatment methods and prevention methods.
In Vietnam: there have been some studies on variations of β2M
concentration in patients with renal failure on hemodialysis, but there is
not any study on the relation between β2M and disorders in patients at
end-stage chronic renal failure on hemodialysis and treatment methods
and prevention methods.
CHAPTER 2: SUBJECTS AND METHODS OF THE STUDY
2.1. Subjects of the study
374 subjects were divided into 2 groups:
+ Patient group: 326 patients on hemodialysis, control group: 48
healthy people with average age and sex ratio equal to patient group.
The topic was conducted at the Department of Hemodialysis,
Bach Mai Hospital from February 2008 to February 2011.
- Inclusion criteria:
+ Control group: Healthy adults, no history of renal-urinary
diseases, equal age and sex to the patient group, agreed to participate
in the study.
+ Patient group:End-stage chronic renal failure, during of
hemodialysis≥ 3 months, age ≥ 18,usinglow flux dialyzer, agreed to
participate in the study.
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intervention group, other groups were randomly selected and also took
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into account equivalent factors.
2.2.1. Clinical examination and laboratory tests
- Each subject in both patient group and control group had a
record according to the study form.
- Subjects in both groups were obtained blood samples to test full
blood counts (FBC) and biochemical indices.
- Control group : fasting blood testing, quantified serum β2M.
- Patient group:
+ Cross-sectional study : obtained blood samples before blood
filtration session, at the first session in week: FBC, β2M, urea,
creatinine, albumin, CRP, uric, phosphorous, cholesterol, triglyceride,
HDL-C, LDL-C, HbAg, Anti-HCV.
+ Intervention study : tested before and after blood filtration (1st
dialyzer), before filtration : blood sampled by needlem after filtration :
blood sampled by slow flow method(FBCobtained before filtration,
biochemical testes before and after filtration: urea, creatinine, β2M,
Albumin, electrolytes, CRP.
2.2.2. Intervention regime
Group 1 (PN1: 64 patients): using lowflux dialyzer only.
Group 2 (PN2: 46 patients): using low flux dialyzer and 2 times
per months with high flux dialyzer.
Group 3 (PN3: 32 patients: usinglow flux dialyzer and 2 times per
month with HDF online.
The first time intervention is called the first time using dialyzer, in
which, group 1 used low flux dialyzer, group 2 used high flux dialyzer
and group 3 used HDF online.
2.2.3. Result assessment
- Cross-sectional study:

Group
Female Male Overall
n % n % n %
Control
n. % 21 43.8 27 56.2 48 100
Mean age
(Years)
34.7 ± 9.9 39.8 ± 9.0 37.56 ± 9.65
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Patient
n. % 140 42.9 186 57.1 326 100
Mean age
(Years)
49.9 ± 13.4 42.3 ± 14.4 45.6 ± 14.5
p > 0.05
The difference between mean ages of control group to patient
group was not statistically significant, p> 0.05.
The ratios of male/female between 2 groups were equal.
Mean ages between two sex groups in both 2 groups were equal.
Table 3.2: Distribution of patients according to age, sex (n=326)
Age group
(year)
Female Male Overall
n % n % n %
≤ 30 14 10.0 47 25.3 61 18.7
31-40 23 16.4 45 24.2 68 20.9
41-50 27 19.3 39 21.0 66 20.2
51-60 44 31.4 35 18.8 79 24.2
>60 32 22.9 20 10.8 52 16.0
Plus 140 42.9 186 57.1 326 100.0

The group of patients with hemodialysis time below 1 years
accounted the smallest percentage.
Table 3.7: BMI characteristics of patients (n=326)
Degree Number (n) Percent (%)
Lacking weight 137 42.02
Normal 167 51.28
Overweight and obesity 22 6.7
Mean (
X
± SD) 19.2 ± 2.4 (13.3 – 29.0)
The percentage of patients with normal BMI accounted the
highest percentages, following by patients lacking of weight (thin).
Table 3.10: Percentage of patients with HBV, HCV (n=326)
Status Number (n) Percent (%)
Not infected 186 57.1
HBV (+) 28 8.6
HCV (+) 98 30.1
HBV and HCV (+) 14 4.2
The percentages of patients infected by hepatitis viruses were
relatively high in this study. There were 30.1% patients had HCV (+),
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8.6% patients had HBV (+) and 4.2% patients had both HBV and
HCV (+).
3.2. Variation of serum beta2-microglobulin concentration in
patients of the study
Table 3.11: Variation of serum beta2 - microglobulin
concentration on patient group and control group
β2M (mg/l)
Subject
Min – Max

Mean values of β2M concentrations between age groups were not
significantly different, this proved that the β2M concentration does not
relate to age of the patient.
Table 3.16: Variation ofserum β2M concentration follwing
hemodialysis time (n=326)
β2M (mg/L)
Hemodialysis
time (years)
Min – Max
X
± SD
<1 (n=14) 23.7 – 70.4 38.2 ± 12.0
1- < 5 (n=183) 16.9-98.7 56.4 ± 18.8
5- <10 (n=107) 43.7-99.9 76.9 ± 12.0
≥10 (n=22) 52.2-129.2 92.4 ± 20.3
p ANOVA < 0.001
Mean β2M concentrations were different between groups of
patients with different hemodialysis times and increased when the
hemodialysis time increased.
Patients with hemodialysis time< 1 yearhad lowest mean β2M
concentration, patients with hemodialysis time above 10 years had highest
mean β2M concentration, the difference was statistically significant with
p < 0.001.
Chart 3.4: Correlation between serum β2M concentration and
hemodialysis time
Hemodialysis time (months)
Serum β2M concentration (mg/L)
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β2M concentration positively significantly correlated with
hemodialysis time. The longer the hemodialysis time ism the higher

of patients with hepatitis virus was significantly higher than patients
without hepatitis virus, p< 0.001.
Table 3.20: Relation betweenserum β2M concentration and
conditions of HBV, HCV infections in patient group
β2M (mg/L)
Hepatitis virus
Min – Max (
X
± SD)
HBV (+). (n=28) 30.3-129.2 62.8 ± 23.5
HCV (+). (n=98) 29.7-120.4 77.6 ± 17.9
HBV + HCV (n=14) 39.4-117.6 78.9 ± 22.9
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p ANOVA < 0.01
When comparing thethreegroups, β2Mlevelsrelatedstrainsof
hepatitisvirusinfection, the differencewas statistically
significant(p<0.01), whichis the highest
inHBV+HCVcoinfectionandthe lowestinthe grouponly infected with
HBV.
Table 3.21: The relation betweenserum β2M concentration and
urine stagnation(n=326)
β2M (mg/l)
Degree
Min – Max (
X
± SD)
No stagnation (n=263) 21.4-129.2 68.2 ± 19.8
Stagnation (n=63) 16.9-109.3 50.5 ± 20.6
P < 0.001
β2M relates to urine stagnation, patients with urine stagnation

Hypertriglyceridemia
No (n=232) 62.7 ± 21.0 <0.01
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Yes (n= 94) 69.8 ± 20.7
Reduced HDL-C
No (n=203) 60.5 ± 19.1
<0.001
Yes (n=123) 71.7 ± 22.7
Increased LDL-C
No (n=256) 63.2 ± 21.2
<0.01
Yes (n=70) 70.6 ± 19.9
β2M relates to dyslipidemiam patients with dyslipidemia had
β2M concentration significantly higher than patients without
dyslipidemia, p < 0.05.
Table 3.25: The relation between serum β2M concentration and
BMI of patient group (n=326)
BMI Number (n)
β2M (mg/L).
(
X
± SD)
Lacking of weight 137 63.83 ± 21.21
Normal 167 65.19 ± 20.43
Overweight, obesity 22 67.17 ± 26.27
p ANOVA > 0.05
β2M concentration tended to increase in overweight/obesity patients,
however β2M does not relate to thin or overweight/obesity, p> 0.05.
3.3. β2M filtration effect in patients used different filtration
methods and dialyzer with different ultrafiltration coefficients

(n=46)
PN3
(n=32)
p ANOVA
Before
filtration
29.2 ± 6.5 29.0 ± 7.1 29.2 ± 7.2 > 0.05
After filtration
9.9 ± 2.6 8.9 ± 2.2 6.0 ± 1.3
1-3.2-3:
< 0.001
1-2: > 0.05
P < 0.001 < 0.001 < 0.001
After filtration, the urea concentration significantly decreased in
all groups, p< 0.001. Group 3 had highest urea-decreasing degree,
significantly different to groups 1 and 2, p < 0.001.
Table 3.31: Comparison of serum creatinine concentration in
groups after the 1
st
time use of dialyzer
Group
Creatinine
(µmol/L)
PN1
(n=64)
PN2
(n=46)
PN3
(n=32)
p

Before treatmen 101.2 ± 16.9 99.2 ± 17.3 99.5 ± 15.1 > 0.05
After 6 months 104.2 ± 16.3 109.6±16.2 120.7 ± 14.3
1-3.2-3:
< 0.05
1-2: >0.05
p > 0.05 < 0.05 < 0.05
Albumin
(g/L)
Before treatmen 38.2 ± 3.5 38.4 ± 5.0 39.7 ± 3.3 > 0.05
After 6 months 38.5 ± 3.4 39.6 ± 4.6 39.0 ± 2.8 > 0.05
p > 0.05 > 0.05 > 0.05
CRP
(mg/dL)
Before treatmen 0.61 ± 0.48 0.47 ± 0.37 0.68 ± 0.49 > 0.05
After 6 months 0.59 ± 0.44 0.52 ± 0.34 0.55 ± 0.33 > 0.05
p > 0.05 > 0.05 > 0.05
BMI
Before treatmen 18.9 ± 2.6 19.6 ± 2.0 19.6 ± 2.4 > 0.05
After 6 months 19.2 ± 2.4 19.5 ± 2.1 21.1 ± 2.0
1-3.2-3:
< 0.05
1-2: > 0.05
p > 0.05 > 0.05 < 0.05
Hemoglobin concentration and BMI in group treated by
hemodiafiltrationwas higher than other groups after 6 moths treatment
and higher than such index before 6 months (p<0.05). There were not
significantly different on number of while blood cells, albumin
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concentration and CRP concentration before and after 6 months
treatment between groups (p > 0.05).

PN2
(n=46)
PN3
(n=32)
p ANOVA
Before filtration (T0) 66.04 ± 26.7 64.8 ± 18.8 69.2 ± 18.9 > 0.05
After 1 month 65.9 ± 26.4 57.8 ± 16.5 46.1 ± 11.8 < 0.05
After 2 months 66.5 ± 26.7 56.3 ± 16.3 44.4 ± 11.9 < 0.05
After 3 months (T3) 66.9 ± 26.6 54.9 ± 16.2 42.7 ± 12.2 < 0.05
After 4 months 67.6 ± 26.5 52.0 ± 15.6 40.8 ± 13.1 < 0.05
After 5 months 68.5 ± 27.0 48.7 ± 14.2 34.5 ± 11.8 < 0.01
After 6 months (T6) 68.5 ± 24.9 46.7 ± 12.8 32.4 ± 9.1 < 0.01
p > 0.05
T6 &T3.
T6&T0:
< 0.001
T6&T3.
T6&T0:
< 0.001
In patients used dialyzer with low ultrafiltration coefficient, the
β2Mconcentration gradully increased.
In patients used dialyzer with low ultrafiltration coefficient
combined with dialyzer with high ultrafiltration coefficient,
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theβ2Mconcentration decreased, after 6 monthes the reduction was
significant p<0.001.
In patients used hemodiafiltration, β2Mquickly decreased, until
the 6th month the concentration was 32.4 mg/L, p< 0.001.
Among groups, there were significant reductions in each month
aboutβ2M,p< 0.05.

the majority, causes of chronic renal failure in theses= countries
related to metabolic disordes, such as diabetes, goutte…
4.1.5. Hepatitis virus infection:the percentage of patients with
hepatitis on hemodialysis highly increased, because the infected with
HBV, HCV via blood rout,. In some developed countries, percentage
of hepatitis lower. This proposes that we should care about prevention
of hepatitis (vaccine, aseptic…).
4.2. Variation of serum beta2-microglobulin concentration and its
relation with some indices in chronic renal failure patients with
maintenance hemodialysis
4.2.1. Variation of β2M
β2M concentration absolutely increased in patient group, the
difference was statistically significant as compared to control group p
< 0.001. The result is consistent with other studies local and abroad.
(Table 3.11).
4.2.2. Relation to sex
Table 3.14: in patients on hemodialysis of our study, both male
and female had increased β2M. But the difference was not significant
with p > 0.05.
4.2.3. Relation to age:In different age groups, β2M concentrations
differed, elder group (61 - 60) had highest β2M concentration but no
sifnificant difference to other age groups, p > 0.05. This result was
consistent because renal failure can not filter β2M and not related to
age.
4.2.4. Relation to hemodialysis time
In this study, β2M concentration related tightly to hemodialysis
time. The longer hemodialysis time, the higher β2M concentration, the
difference between groups was significant with p < 0.001 (Table 3.16).
This is due to β2M produced every day, low ultrafiltration can not
clear β2M leading to deposition of β2M.

time, age, β2M concentration and other indices.
Urea, creatinine filtration effect on the first time use dialyzer :
good in all 3 goups. the difference between before and after filtration
was statistically significant with p < 0.001. But the effect was highest
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in HDF online group.
Effect on regulation of some electrolytes.Electrokytes (Na
+
, K
+
,
Cl
-
) before and after filtration in all 3 groups were equivalent, effect on
electrolyte balancing in 3 groups were equal.
Variation of some indices after 6 months treatment: In 3 groups
after 6 months treatment, HDF online group improved anemia,
hypertension. Other indices like: albumin, CRP, white blood cells
were not different in 3 groups.
4.3.2. β2M filtration effect in groups
Filtration effect in the first time use : results of the study (table
3.38) show that in group 1, the β2M concentration slightly increased
after filtration, so this group was not efftectively filtered β2M ; in
group 2, the β2M concentrations before and after filtration were
significantly different with p < 0.01. The filtration effect was very high
in group 3. Thus, HDF online is the most effective method for
filtration of β2M as compared to 2 other groups.
Variation of β2M concentration after 6 months treatment.
After 6 months treatment, in the group used dialyzer with low
ultrafilatrion coefficient, the β2M concentration tended to increase. In

than in patients with urine stagnation (68.2 ± 19.8 mg/L vs 50.5 ± 20.6
mg/L).
+ β2M concentration related significantly to albumin level. In
patients with decreased albumin levels, β2M concentration higher than
in patients with normal albumin levels (69.32 ± 19.87 mg/L vs 60.89 ±
22.99 mg/L).
+ β2M related significantly to dyslipidemia. Mean value ofβ2M
concentrations increased in patients with increased cholesterol,
triglyceride, LDL-C or decreased HDL-C.
2. β2M filtration effect when using methods and dialyzers with
different ultrafiltration coefficients.
+ After the first time use, only mean serumβ2M concentrations in
patients used hemodiafiltration online and patients used dialyzer with
low ultrafiltration coefficient in combination with dialyzer with high
ultrafiltration coefficient significantly decreased as compared to before
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filtration (69.2 ± 18.9 mg/L vs 21.8 ± 9.8 mg/L and 64.8 ± 18.8 mg/L
vs 47.8 ± 13.5 mg/L), p< 0.001. Average bloodβ2M concentration
after filter by Hemodiafiltration online was lower than the group used
dialyzer with low ultrafiltration coefficient in combination with
dialyzer with high ultrafiltration coefficient, p< 0.001.
+ Among 3 groups, clearance index of bloodβ2M after the first
time filtration in group combined with hemodiafiltration online was
highest, significantly different to group combined with using dialyzer
has high ultrafiltration coefficient and the group only used dialyzer has
low ultrafiltration coefficient (52.4 ± 6.8 mg/Lvs 32.5 ± 5.7 mg/Land
6.2 ± 4.2 mg/L), pANOVA < 0.001.
+Mean value of serumβ2M concentrations decreated after 6
months treatment when combined with Hemodiafiltration online and
when combined with dialyzer has high ultrafiltration coefficient (69.2 ±


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