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

1 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 2 β2M filtration after the session, but there is not any study on the relation between some factors can cause increaseβ2M concentration and treatment methods. Therefore, we conducted this topic with 2 following objectives: 1. To investigate the serumbeta2-microglobulin concentration and its relation to some indices in patients with chronic renal failure on hemodialysis using low flux dialyzer. 2. To compare the results of beta2-microglobulin filtration using 3 methods: using membrane with low ultrafiltration coefficient alone, using membrane with low ultrafiltration coefficient in combination with membrane with high ultrafiltration coefficient and using membrane with low ultrafiltration in combination with hemodiafiltration online(HDF online). 2. New contributions of the topic This is the first study in our country assessing the variation in β2M concentrations and the relation between β2M concentration and some features in patients with chronic renal failure on hemodialysis. In addition, the study also assessed results of β2M filtration in some blood dialysis method in order to offer the optimal treatment method that reduces β2M concentration to void future complications caused by β2M, and to enhance life quality of patients on hemodialysis. 3. Structure of the thesis:The thesis includes123pages. Forewords: 2 pages, overview: 33 pages, Subjects and methods of study: 23 pages, Study results: 28 pages, Dicussion: 34 pages, Conclusions and Recommendations : 3 pages. The thesis contains 51 tables, 10 charts, 1 diagram, 3 figure. The thesis reffered 145 references including 32 Vietnamese and 113 English references. 3 CHAPTER 1: OVERVIEW 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. 4 - Peritoneal dialysis : accounted about 16%, done at home, the patient does not depend on the hospital and medical professionals but it remains many complications and less effective than artificial kidney. - Blood filtration outside the body(maintenance hemodialysis) accounted 69%. This method is widely used because it is easy to implement but the disadvantage is the patient depends on devices and hospital. 1.4. Replace the damaged kidney with maintenance hemodialysis Artificial kidney or maintenance hemodialysis can be done at home, at the dialysis center or hospital. In Vietnam, currently hemodialysis is done at hospital. Hemodialysis includes following methods: + Intermittent hemodialysis : 3 times per week, 4 hours per time (IHD) or hemodialysis at home with frequency of 6-7 times per week, about 2 hour each time. In this method, many types of dialyzers can be used - low ultrafiltration coefficient (Low flux) average ultrafiltration coefficient (Midium flux) high ultrafiltration coefficient (High - flux). + Hemofiltration (HF): convective mechanism. + Hemodiafiltration(HDF): mechanism combining convection and diffusion, HDF includes HDF online and HDF off -line. Fluid compensation can be done before membrane, at middle of membrane, after membrane or before and after membrane. HDF method has more advantages since it applies both convecton and diffusion mechanisms at the same time. 1.5. Beta2-microglobulin in chronic renal failure and hemodialysispatients β2M is a component ofmajor histocompatibility complex molecules, which presents on all nucleated cells, and belongs to the group of average molecular weight substances (11800 dalton). 5 β2M presents in blood with a concentration < 2mg/dl, and is filtrated through glomerular. 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. 6 -Exclusion criteria: Control group: Suffering from some chronic diseases such as rheumatoid arthritis, chronic gastro-duodenum diseases…obesity, drinking alcohol, pregnant women, nursing mothers. Patient group: Patients with heart failure symptoms: frequent dyspnea, chest pain, enlarged heart on X-ray image… Patients with hepatic diseases: ascites, cirrhosis on image obtained from ultrasound technique, collateral circulation. Patients with end-stage cancers, acute diseases such as: infection, myocardial infarction, acute heart failure, stroke… Patients with difficults in creating a way reaching the blood vessel affecting the quality of hemodialysis. Patients suspected to have external diseases or had been intervened by surgery within 1 moth. Patients did not collaborate. Inclusion criteria of intervention patients (using dialyzers : Low flux, Low flux + High-flux, Low flux + HDF online). Among 326 patients, selected 32 patients agreed to have hemodialysisLow flux + HDF online (after the patients were explained about advantages, disadvantages, and mandatory procedures that they must comply). 294 patients were divided into small groups and randomly selected 1 group with age, sex, during of hemodialysis, cause of renal failure, β2 concentration equal to the HDF online group,in this group 46 patients were selected with Low flux + High flux. Low flux group: among remaining patients, similarly to group 2, 64 patients were selected. 2.2. Methods of the study - This is a cross-sectional descriptive study with control group in combination with a follow up-intervention study. - Patients were selected with clinically convenient sample size, the intervention group was divided into 3 goups, selected the HDF online intervention group, other groups were randomly selected and also took 7 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: + Assessed the variation of serumβ2M concentration in patients with chronic renal failure on hemodialysis as compared to control group. 8 + Assessed the relation between serum β2M concentration in patients with chronic renal failure on hemodialysis and factors: age, sex, dialysis time, BMI, serum CRP, serum phosphorous, serum urea, serum creatinine, serum lipids… - Intervention study: + Assessed the filtration results ofserum urea, creatinine, β2M in methods using first-time-use dialyzer. + Assessed the reduction of serum β2M after 6 moths treatment with each method. 2.2.4. Ethics - Do not violate ethics in study. - Tests and treament methods are done for the benefit of patients. -Tests performed according to instructions in the recommendations. - Respect opinions of the study subjects, subjects have right to refuse. - Data is collected accurately, honesty and confidentially. 2.2.5. Data processing Data was processed by biostatistics method using softwares Epi- Info 3.5.1 and Epical 2000. Mean values, standard deviation, percentage, compared 2 mean values and percentages by t-test, compared many percentages by test χ 2 , compared many mean values by Anova, calculated correlation coefficient r. CHAPTER 3: RESULTS OF THE STUDY 3.1. General characteristics of subjects of the study Table 3.1: Comparison of age, sex between 2 groups 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 9 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 Distribution of patients was relatively even between age groups, however, the group of patients ≤ 30 years old and> 60 years old had smallest percent. This study mainly included patients aged from 31 to 60 years old (65.3%). The ratio of male/female in each age groups were equal. Table 3.3: Causes of chronic renal failure Cause Number (n) Percent (%) Chronic glomerulonephritis 230 70.6 Chronic Pyelonephritis 43 13.2 Diabetes 32 9.8 Others 21 6.4 Plus 326 100% 10 The percentages of patients according to causes in the stidy were different. Chronic renal failure caused by chronic glomerulonephritis accounted the highest percentage (70.6%). Table 3.4: Distribution of patients according to the hemodialysis time (n=326) Hemodialysis time (years) Number (n) Percent (%) <1 14 4.3 1- <5 183 56.1 5- <10 107 32.8 ≥10 22 6.7 Mean ( X ± SD) 4.71 ± 3.14 (years) The group of patients with hemodialysis time above 1 year and below 5 years accounted the highest percentage. 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 (+), [...]...11 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) Min – Max p X ± SD Subject Patient (n=326) 16.9 - 129.2 64.7 ± 21.1 < 0.001 Control... hemodialysis should be applied this method to obtain the highest treatment effect CONCLUSIONS Study on serumβ2 microglobulin concentrationin 326 patients on hemodialysis using dialyzer with low ultrafiltration coefficient, comparing to 48 healthy people in control group and assessing the Beta2 microglobulin filtration effect in patients using methods and 23 dialyzers with different ultrafiltration coefficients... 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... with low ultrafiltration coefficient then theβ2M concentration tended to increase (66.04 ± 26.7 mg/L vs 68.5 ± 24.9 mg/L) RECOMMENDATIONS + Patients on hemodialysis should be regularly tested serumβ2 microglobulin concentration and factors affecting β2M concentration to provide basis for diagnosis, prognosis and treatment of chronic renal failure in order to increase life quality of patients + To control . the serumbeta2-microglobulin concentration and its relation to some indices in patients with chronic renal failure on hemodialysis using low flux dialyzer. 2. To compare the results of beta2-microglobulin. and using membrane with low ultrafiltration in combination with hemodiafiltration online(HDF online). 2. New contributions of the topic This is the first study in our country assessing the variation. more advantages since it applies both convecton and diffusion mechanisms at the same time. 1.5. Beta2-microglobulin in chronic renal failure and hemodialysispatients β2M is a component ofmajor