uremia related , non -traditional risk factors , such as inflammation , oxidative stress , dyslipidemia , vascular calcification alterations in calcium and phosphorus ( p ) metabolism , have been proposed to play a central role ( 2 ) .
elevated plasma beta2 microglobulin ( 2 m ) , is a well - known characteristic of chronic renal failure .
predialysis serum 2 m level predicted mortality and increase of 2 m clearance during hd was associated with improved outcomes ( 3 ) .
the source of the elevated serum 2 m in hemodialysis patients , has not been explained absolutely .
there is controversy as to whether elevated levels are caused predominantly by increased synthesis , the use of membranes in hemodialysis with different clearance capacities , or diminished renal elimination .
use of middle and high - flux biocompatible membranes was shown to be associated with a notable reduction 2 m ( 4 ) .
the surface of lymphocytes and monocytes are particularly rich in 2 m , the latter being synthesized to large amounts by lymphocytes and regulated by interferons and proinflammatory cytokines ( 5 ) , which might explain the pathophysiological  role  in atherosclerosis . but remains to be further clarified if 2 m is solely a marker of inflammation or if it has a direct pathogenic effect and if other yet unknown confounders may influence 2 m levels ( 6 ) .
the uremic state is associated with an altered immune response , and intermittent stimulation by endotoxins originating from the dialysis water supply and artificial vein grafts or bio incompatibility caused the increased circulating inflammatory proteins , such as c - reactive protein ( crp ) ( 7 ) , produced by the liver , mainly in response to interleukin -6 ( il-6 ) .
hemodialysis patients , exhibit significant alterations in lipoprotein metabolism , which in their most advanced form result in the development of severe dyslipidemia .
lipid disorders stem largely from dysregulation of high density lipoprotein ( hdl ) and triglyceride - rich lipoproteins metabolism .
the down regulation of the expression of several genes along with the changes in the composition of lipoprotein particles and the direct inhibitory effect of various uremic 
toxins on the enzymes involved in lipid metabolism , represent the most important pathophysiological mechanisms underlying the development of hypertriglyceridemia ( 8) .
several mechanisms , working in concert , may underlie the reduction in hdl levels , which is usually indicative of impaired reverse cholesterol transport .
thus , uremic patients exhibit decreased levels of apolipoproteins ai and aii , diminished activity of lecithin - cholesterol acyl - transferase , as well as increased activity of cholesteryl ester transfer protein that facilitates the transfer of cholesterol esters from hdl to triglyceride - rich lipoproteins , thus reducing the concentration of hdl ( 8) .
lipoprotein(a ) [ lp(a ) ] is an independent risk factor for clinical events attributed to atherosclerotic cardiovascular disease in chronic hemodialysis .
lp(a ) levels are frequently elevated in hd patients ( 9 ) and are considered a major risk factor for cardiovascular disease ( 10 ) .
secondary hyperparathyroidism , is one of the major complications of patients in chronic hemodialysis ( 11 ) .
parathyroid hormone ( pth ) starts to rise very early in the course of kidney disease .
as disease progresses , plasma levels of vitamin d and calcium begin to decline , thus contributing to greater secretion of pth . in addition
, the retention of phosphate further increases pth secretion independent of calcium and vitamin d levels .
previous studies have supported the view that high pth serum levels in uremic patients may cause deleterious effects in myocardium metabolism and function ( 12 ) .
the aim of this study is to investigate the association of 2-m with inflammatory markers , dyslipidemia and mineral disorders in high - flux membrane hemodialysis patients .
in study were included 40 patients , undergoing maintenance high - flux membrane hemodialysis treatment in the clinical centre in prishtina , for a period longer than 6 months .
a ) based in patient s history , angina , possible myocardial infarction , cerebrovascular events , infective diseases and cancer , were excluded . in all patients , 2-m , crp , il-6 , triglycerides , cholesterol , ldl , hdl , lp(a ) , pth , calcium ,
triglycerides , cholesterol , hdl , ldl , calcium , phosphorus and albumin were measured by biochemical analysis ; b ) the assay of -2 microglobulin is based on a latex enhanced immunoturbidimetric method .
c ) crp was determined by the turbidimetric method , il-6 with enzyme linked immunosorbent immunoassay ( elisa ) , lipoprotein ( a ) with immunoturbidimetric method depth with a chemiluminometric immunoassay ; d ) twenty - four healthy subjects ( 12 women and 12 men , aged 56.08  12.34 years ) served as controls .
serum concentration of 2 m , crp , il-6 , triglycerides , lp(a ) , p and pth in hemodialysis patients were significantly higher than in controls ( 19.84  2.23
mg / l vs 2.11  1.0 mg / l , p<0.001 ; 39.75 29.7 mg / l vs 16.25  3.78mg / l , p<0.001 ; 3.06  1.08 pg / ml vs 0.35  0.3 pg / ml , p < 0.001 ; 3.17  1.28
mmol / l vs 1.19  0.38 mmol / l , p<0.001 ; 40.25  12.98 mg / dl vs 24.33  8.51 mg / dl , p<0.001 ; 1.9  0.6
mmol / l , p<0.001 ; 137.35  50.7 pg / ml vs 46.56  28.64
the concentration of hdl and serum albumin was significantly lower ( 1.14  0.34 vs 1.52  0.35 mmol / l , p<0.001 ; 34.83  3.89
g / l vs 40.5  3.94 g / l , p<0.001 ( table 1 ) .
we did not find any difference in cholesterol , ldl and calcium levels between two groups ( 4.0  1.11mmol / l vs 4.26  0.16
mmol / l , p=0.16 ; 2.90  1.14 mmol / l vs 2.41  0.57
mmol / l , p<0.05 ; 2.2  0.24 mmol / l vs 2.26  0.25 mmol / l , p = 0.11 ( table 1 ) . biochemical parameters in hemodialysis patients and controls 2 m
was inversely associated with hdl , albumin and calcium concentration ( r = -0.73 , p < 0.001 ; r = -0.53 , p < 0.001 ; r = -0.50 , p < 0.01 ( table 2 ) , whereas positively was associated with triglycerides , p and pth ( r= 0.69 , p < 0.001 ; r= 0.53 , p < 0.001 ; r=0.58 , p < 0.05 ( table 2 ) .
the patients with high 2 m values , simultaneously had higher lp(a ) concentrations , but we did not observe significant correlation ( r=0.28 ( table 2 ) .
we also found low positive correlation of 2 m with age ( r=0.46 , p < 0.001 ( table 2 ) .
2 m levels were upper in patients with high crp levels , but there was no significant relationship between crp or il-6 and 2 m ( r= 0.11 , p <
0.001 ; r= 0.23 , p < 0.001 ( table 2 ) . there was no correlation of 2 m with cholesterol and ldl cholesterol ( r = 0.13 , p < 0.001 ; r = 0.18 , p < 0.001 ( table 2 ) .
positive correlation exists between crp and il-6 ( r=0.94 , p < 0.001 ( table 2 ) .
albumins correlated negatively with il-6 and lpa ( r = -0.60 , p < 0.001 ; r=-0.72 , p<0.005 ( table 2 ) .
correlation between serum 2 m levels with selected biochemical parameters during the follow - up period of three years , 6 out of 40 patients had died , from cardiovascular events .
significant correlation exists between b2 m and glomerular filtration rate even when renal function was only slightly impaired .
liabeuf , et al , reported plasma 2 m level to be a predictor of cardiovascular events and mortality in patients with different stages of chronic kidney disease ( 14 ) .
we examined the impact of 2 m on some cardiovascular risk factors in high - flux membrane hemodialysis patients . a correlation between an inflammatory response during hemodialysis and elevated serum 2 m has been described ( 15 ) .
compared with the controls , hd patients exhibited marked elevation of serum 2 m , crp and il-6 ( 19.84  2.23 mg
29.7mg / l vs 16.25  3.78mg / l , p<0.001 ; 3.06  1.08 pg / ml vs 0.35  0.3 pg / ml , p < 0.001 ( table 1 ) .
but we found no relationship between crp or il-6and 2 m ( r= 0.11 , p < 0.001 ; r= 0.23 , p < 0.001 ( table 2 ) when high - flux membranes are used .
( 16 , 17 , 18 ) . even in studies , where the low flux membranes were used
our findings suggested that plasma b2 m level is directly correlated with some metabolic and cardiovascular risk factors .
triglycerides start to increase in early stages of chronic kidney disease and show the highest values in dialysis patients .
hemodialysis patients presented increased triglycerides compared with controls ( 3.17  1.28 mmol / l vs 1.19  0.38 mmol / l , p<0.001 ( table 1 ) .
we find significant positive correlation between triglycerides and 2 m levels ( r= 0.69 , p < 0.001 ( table 2 ) .
hdl concentrations exhibited significant reduction in patients compared to controls ( 1.14  0.34 vs 1.52  0.35 mmol / l , p<0.001 ( table 1 ) .
serum 2 m concentrations were inversely associated with hdl ( r = -0.73 , p<0.001 ( table 2 ) .
supporting , linear regression analysis confirmed the negative impact of 2 m concentrations on hdl level .
lp(a ) start increasing early during the course of chronic kidney disease and becomes pronounced with increasing severity of disease .
lp(a ) levels were significantly higher in patients than in controls ( 40.25  12.98 mg / dl vs 24.33  8.51 mg / dl , p<0.001 ( table 1 ) , which confirm that kidney have an important role in lp(a ) metabolism .
the patients with high 2 m values , simultaneously had higher lp(a ) concentrations but we did not observe high correlation ( r=0.28 , p<0.05 ( table 2 ) .
the negative correlation of lp(a ) with albumin ( r=-072 , p<0.005 ( table 2 ) , suggests that the mechanism behind the increased lp(a ) levels may be related to the protein losses , perhaps via an increased synthesis rate of apolipoprotein ( a ) in the liver or via decreased lp(a ) catabolism in hd patients .
we found a significant indirect relationship between 2 m and albumin ( r=-0.53 , p<0.001 ( table 2 ) .
this correlation may be used to identify the patients at high risk , from cardiovascular disease ( 22 ) .
mineral and bone disorder is a growing health care concern associated with secondary hyperparathyroidism , mineral abnormalities , and increased risk of cardiovascular disease ( 23 ) . in hemodialysis patients , concentrations of pth and p
were significantly higher compared with controls ( 137.35  50.7 pg / ml vs 46.56  28.64
pg / ml , p<0.001 ; 1.9  0.6 mmol / l vs 1.26  0.33
calcium levels were lower in patients compare with controls , but with no significant difference ( 2.2  0.24
mmol / l vs 2.26  0.25 mmol / l , p = 0.11 ( table 1 ) .
mineral and bone disorders are associated with accelerated atherosclerosis ( 24 ) , which is an important cause of cardiovascular death in chronic hemodialysis ( 25 ) . in this study ,
serum concentration of 2 m positively correlated with p and pth ( r= 0.53 , p < 0.001 ; r=0.58 , p < 0.05 ( table 2 ) , whereas negatively with calcium ( r = -0.50 , p < 0.01 ( table 2 ) , which proves that 2 m has direct impact in mineral disorders and cardiovascular risk in hd patients . it has been suggested that the predictive value of serum 2 m concentration is superior to that provided by established prognostic factors for mortality , such as glomerular filtration , cystatin c and crp ( 26 ) . during the follow - up period of three years , 6 out of 40 patients had died from cardiovascular events .
even if there was no correlation of 2 m with inflammation , in high - flux membrane hemodialysis patients , our finding indicates that 2 m might have an important role in the development of cardiovascular diseases .
 background : higher than expected cardiovascular mortality in hemodialysis patients , has been attributed to dyslipidemia as well as inflammation . 
 beta2-microglobulin ( 2 m ) is an independent predictor of outcome for hemodialysis patients and a representative substance of middle molecules.results:in 40 patients in high - flux membrane hemodialysis , we found negative correlation of 2 m with high density lipoprotein ( r=-0.73 , p<0.001 ) and albumin ( r= -0.53 , p<0.001 ) and positive correlation with triglycerides ( r=0.69 , p<0.001 ) , parathyroid hormone ( r=0.58 , p < 0.05 ) and phosphorus ( r= 0.53 , p<0.001 ) . 
 there was no correlation of 2 m with c- reactive protein ( crp ) and interleukin-6 ( il-6 ) . during the follow - up period of three years 
 , 6 out of 40 patients have died from cardiovascular events.conclusion:in high - flux membrane hemodialysis patients , we observed a significant relationship of 2 m with dyslipidemia and mineral bone disorders , but there was no correlation with inflammation . 