Year : 2003 | Volume
: 14 | Issue : 4 | Page : 492--496
The Clinical Significance of β2-microglobulin in End-Stage Renal Disease
Iqdam K Al-Taee1, Jenan J Al-Safar2, Yasine S Al-Falahi2, Ihsan A Al-Shamma3,
1 Department of Nephrology and Dialysis, Rasheed Center of Postgraduate Medical Teaching, Rasheed Hospital, Baghdad, Iraq
2 Department of Immunology, Rasheed Center of Postgraduate Medical Teaching, Rasheed Hospital, Baghdad, Iraq
3 Department of Nephrology, Rasheed Center of Postgraduate Medical Teaching, Rasheed Hospital, Baghdad, Iraq
Iqdam K Al-Taee
Rasheed Hospital, P.O. Box 3712, Alwiya, Baghdad
β2-microglobulin is a non glycosylated single chain protein present in light chain of HLA-class I. It is synthesized in the body and excreted in the urine. Its level increases in the blood of the chronic renal failure patients and may deposit in the soft tissue as β2-microglobulin derived amyloidosis, which appear clinically after 5 years of dialysis. We studied 64 patients (49(76%) men) with end stage renal disease (ESRD) on regular hemodialysis. The mean age was 34.3 ± 12 years and the duration of dialysis ranged between 0.4-12 years. Twenty-five healthy persons with mean age 34 ± 17.6 years were used as a control group. The blood level of β2-M in the control group ranged from 0.73-3.81 mg/l, while the range in the study group was 5.2-51.8 mg/l. In the urine of the control group, β2-M level ranged from 0-0.7 mg/l, while in the control group it ranged from 0.07-11.8 mg/l. There was significant difference in the β2-M level in both control and study groups. A direct correlation was found between the duration of dialysis and the level of β2-M in the blood. The traditional low flux dialyzer membrane had no effects on β2-M level in our series. We conclude that there is increased tendency with time for retention of β2-M in the ESRD patients on chronic dialysis. Using dialyzers with high flux synthetic membrane (e.g. acrylonitrile, polyamide, and polysulphone) rather than the low flux membrane may allow substantial removal of β2-M molecules, especially in patients who have little chance of receiving renal transplantation.
|How to cite this article:|
Al-Taee IK, Al-Safar JJ, Al-Falahi YS, Al-Shamma IA. The Clinical Significance of β2-microglobulin in End-Stage Renal Disease.Saudi J Kidney Dis Transpl 2003;14:492-496
|How to cite this URL:|
Al-Taee IK, Al-Safar JJ, Al-Falahi YS, Al-Shamma IA. The Clinical Significance of β2-microglobulin in End-Stage Renal Disease. Saudi J Kidney Dis Transpl [serial online] 2003 [cited 2021 Mar 4 ];14:492-496
Available from: https://www.sjkdt.org/text.asp?2003/14/4/492/32915
Beta-2 microglobulin (β2-M) is a nonglycosylated low molecular weight single chain protein (11.8 Kilo Dalton) found on all nucleated cells and shed in to the blood stream especially when lymphocytes are activated during inflammation. It is a subunit of class-I human leukocyte antigen (HLA) molecule being present in light chain which in conjunction with class-II molecule, directs self and non-self discrimination at the beginning of immune response.
This association of β2-M with HLA system and, in particular, the antigen presenting cells (APC) is important for cellular immune response in chronic renal disease.
The normal synthesis rate of β2-M is 2-4 mg/kg/day and the normal plasma level is 1-4 mg/l, which varies inversely with glomerular filtration rate (GFR). Usually it is filtered through the renal glomeruli and part of it is absorbed and catalyzed by the renal tubular cells, while the non-absorbed part is excreted in the urine.
In end stage renal failure (ESRF), the daily synthesis of β2-M is normal but its level in the blood is increased due to impaired excretion by the kidney. It may be increased sixty folds above normal and start to deposit in certain tissues causing a form of amyloidosis usually present as a serious complication of longterm hemodialysis (HD). , It has recently been described in continuous ambulatory peritoneal dialysis (CAPD) and pre-dialysis patients too. 
This form of amyloidosis was established by Gejio et al in 1985 and was first called dialysis associated amyloidosis (DAA) and changed later to β2-M derived amyloidosis. Finally, name was changed to A β2-M amyloidosis according to the type of amyloid (ALtype). 
Aβ2-M amyloidosis is a systemic disease largely confined to the musculo skeletal system with a predilection to acromioclavicular, elbow, shoulder, wrist and hip joints. , Carpal Tunnel Syndrome (CTS) is a common feature of this disease.  The exact pathogenesis is not known  but there are many risk factors, which may predispose to the disease, including:
(1) Older age of patients: as no cases were reported in pediatric dialysis patients.
(2) Duration on dialysis therapy: since amyloid deposition precede clinical symptoms of the disease which rarely present before 5 years of continuous dialysis and its incidence will increase 100% after 15 years.
(3) Type of the dialyzer membranes: where low flux membrane does not clear β2-M molecules from the blood. A partly positive effect of high flux membrane dialyzer was suggested. ,,
(4) Impure water and acetate buffer increase the rate of synthesis of A β2M and level in blood. Using ultrapure water in dialysis and bicarbonate buffer dialysate may decrease the incidence of Aβ2-M amyloidosis. ,
Histopathology is still the cornerstone in the diagnosis of A02-M amyloidosis. Therefore, it is desirable to diagnose the disease before it becomes clinically evident in order to prevent its complications.
The aim of this study is to estimate the level of B2-M in the blood and urine of uremic patients on chronic hemodialysis and study the clinical course and its relation to the types of the dialyzer membrane.
Patients and Methods
We studied 64 patients with ESRD on regular HD therapy. There were 49(76%) men with age range between 10-63 years (mean 34.3 ± 12.). The duration of hemodialysis ranged from 0.4-12 years. All our patients had negative HbsAg, HCV, and HIV tests. All patients were on low flux cuprophan dialyzers and acetate based dialysate.
We reviewed the medical records of the patients including the routine laboratory investigations. We also obtained serum protein electrophoresis, serum immunoglobulins and β2-M level in both blood and urine on all the study patients. Special kits were used to measure β2-M level, from BioMerieux using ELISA technique and from DiaSorni using radioimmuno assay (RIA) and Gamma counter.
β2-M levels where also measured in the blood of 25 healthy controls with a mean age of 34 ± 17. 6 years.
All data where statistically analyzed using (student t-test and F-test) according to the number of variables tested. P ,
Appearance of β2-M in the urine depends on its plasma level, when exceeding its renal reabsorptive threshold of 5 mg/l. This will explain why the urinary β2-M becomes high when its plasma level is increased. The excess β2-M in the urine can damage the renal tubular cells, by release of the pro-inflammatory cytokines and probably the reactive oxygen metabolites. 
The serum total protein and albumin are low in the study group. This is probably because of malnutrition and/or urinary protein loss due to the original disease of the kidney, which caused ESRD, while β-globulin level is increased because of being acute phasereactant and also serum IgG level since it is a marker of chronicity of the disease.
In our study patients, as the duration on dialysis therapy increased the blood and consequently the urinary level of β2-M significantly increased. The findings in the subgroups also indicate that the risk of the AB2-M amyloidosis increases in a linear pattern especially after 5 years of HD therapy. Urine values depend on the residual GFR and renal tubular function. Accordingly, the urine values of B2-M in our study were lower than the blood values because of renal failure.
Different types of dialyzer membranes have different sieving coefficient for β2-M. Low flux cuprophan having the poorest and the synthetic membranes like polysulphone and polyacrylonitrile having the best coefficient. ,,, We tested the effect of only the low flux dialyzers on the blood levels of β2-M and - did not find any effect on it.
We conclude that there is increased tendency with time for retention of β2-M in the ESRD patients on chronic dialysis. Using dialyzers with high flux synthetic membrane (e.g. acrylonitrile, polyamide, and polysulphone) rather than the low flux membrane may allow substantial removal of β2-M molecules, especially in patients who have little chance of receiving renal transplantation.
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