a major factor leading to cardiovascular disease in hemodialysis patients is vascular calcification , which causes vascular stiffness , higher pulse wave velocities , and elevated pulse pressures . it is thought that vascular calcification is caused by disrupted mineral metabolism and abnormal regulation of phosphorus and calcium . fibroblast growth factor 23 ( fgf-23 ) is an osteocyte - derived hormone that participates in phosphate and vitamin d metabolism . elevated fgf-23 levels are observed in phase 2 of chronic kidney disease and are inversely correlated with glomerular filtration rate . patients with esrd may reach fgf-23 blood levels around 101000 times higher than normal . even within the normal range , a strong association was observed between high serum fgf-23 levels and atherosclerotic burden , endothelial dysfunction , and arterial stiffness . elevated fgf-23 serum levels are particularly implicated in the calcification of peripheral vasculature and the coronary artery . high - flux hemodialysis ( hfhd ) is a dialysis procedure designed to eliminate blood toxins that accumulate in esrd . whether hfhd is better than low - flux hemodialysis ( lfhd ) is still under debate . in this study , we compared the efficacy of hfhd and lfhd in reducing vascular calcification and serum fgf-23 levels in patients receiving maintenance hemodialysis . the study was conducted according to the declaration of helsinki and was approved by the ethics committee of xiangya hospital , zhongnan university . this study was registered as a clinical trial ( chinese clinical trial registry , www.chictr.org.cn , chictr - opc-15006249 ) . from june 2013 to june 2014 , fifty patients receiving maintenance hemodialysis were recruited to participate . inclusion criteria was as follows : 1880 years of age , previously treated with hemodialysis for at least 3 months ( 3 per week ; 4 h per session ) , dry weight was relatively stable , arteriovenous fistula was created for hemodialysis , and blood flow rate was 200 ml / min . exclusion criteria were as follows : patients with severe infections in the past three months , hepatic disease , or previous hemodiafiltration or peritoneal dialysis treatments . patients were randomly allocated into either the hfhd group or the lfhd group ( 25 per group ) . patients received respective treatments for 12 months , which was performed 4 h per session three times per week . the hemodialysis machines utilized in this study were a fresenius 4008s ( bad homburg , germany ) and a gambro ak96 ( lund , sweden ) . the dialysate flow rate was set at 500 ml / min , blood flow was set at 250300 ml / min , and the urea clearance index ( kt / v ) was 1.2 . a ca - hp170 dialyzer ( baxter , deerfield , usa ) was used for lfhd . the surface area of the tri - cellulose acetate ( tca ) membrane was 1.7 m and the ultrafiltration coefficient was 10.0 ml / hr / mmhg . a ct-190 g dialyzer ( baxter , deerfield , usa ) was utilized for hfhd . the surface area of the tca membrane was 1.9 m and the ultrafiltration coefficient was 36.0 ml / hr / mmhg . fasting venous blood was collected at baseline , six months , and twelve months after treatment . fgf-23 levels were measured by commercial elisa kits ( millipore inc , usa ) according to the manufacturer s instructions . calcium , phosphorus , akp , albumin , creatinine , and lipid levels were measured by standard methods . aorta abdominalis calcification scores ( aacs , figure 1 ) were calculated according to the length of calcified deposits on the anterior and posterior walls of the aorta abdominalis , which corresponds to lumbar vertebrae 14 . anterior and posterior calcification scores were recorded separately for each vertebra ( i.e. eight separate scores were recorded ) . scoring was performed blindly by two independent doctors as follows : 0 point , no calcification ; 1 point , calcification of < 1/3 of the vascular wall ; 2 points , calcification of 1/32/3 of the vascular wall ; 3 points , calcification of > 2/3 of the vascular wall [ 2123 ] . final aacs were calculated by summing the eight separate scores , ranging from 0 to 24 points . t - tests were performed for comparing between different groups of the patients characteristics data . repeated measures analysis of variance was used to examine changes in serum calcium , phosphorus , pth , akp , fgf-23 , and aacs from baseline to 12 months after treatment . multiple regression analyses were also carried out to screen potential factors influencing the development of vascular calcification . these factors included age , duration of hemodialysis , blood pressure , fgf-23 levels , therapy alternatives , blood calcium levels , and blood phosphorus levels . seventy - three patients were initially screened in the study . however , 7 patients declined to participate and 16 patients were excluded ( 2 cases for severe infection within 3 months , 11 cases for hepatic disease , and 3 cases for previous hemodiafiltration or peritoneal dialysis treatments ) . the remaining 50 patients were randomly allocated into either the hfhd or lfhd group ( 25 in each ) . the hfhd group included 23 chronic glomerulonephritis patients , one diabetic nephropathy patient , and one obstructive nephropathy patient . the lfhd group was comprised of 19 chronic glomerulonephritis patients , four diabetic nephropathy patients , and two hypertensive nephropathy patients . over the one - year follow - up period , one hfhd participant was excluded for receiving a kidney transplant . in the lfhd group , one patient was excluded for kidney transplants , one patient died , and three others dropped out of the study . no significant differences in basic patient characteristics ( e.g. age , sex , co - morbidity diseases , blood pressure , lipid levels , and kt / v ) were detected between the hfhd and lfhd groups ( p>0.05 ; table 1 ) . six months after treatment , we found no significant difference in calcium , phosphorus , parathyroid hormone ( pth ) , alkaline phosphatase ( akp ) , fgf-23 , or aacs between the two groups ( p>0.05 ) . after 12 months of treatment , fgf-23 levels and aacs significantly decreased in the hfhd group , but not the lfhd group ( p=0.049 and p=0.002 , respectively ; table 2 ) . fgf-23 levels and aacs in the hfhd group decreased by 41.423.4% and 30.040.3% respectively , while they increased by 0.326.4% and 76.45.6% in the lfhd group , respectively . pearson correlation analysis revealed that aacs were positively correlated with fgf-23 levels in all patients ( p=0.004 ; figure 2a ) , the hfhd group alone ( p=0.040 ; figure 2b ) , and the lfhd group alone ( p=0.037 , figure 2c ) . multiple regression analysis indicated that older patients ( p=0.048 ) , those with higher blood phosphorus levels ( p=0.003 ) , and higher fgf-23 levels ( p=0.001 ) had significantly increased risks of aorta abdominalis calcification . it also showed that hfhd reduced the risk of aorta abdominalis calcification , compared to lfhd ( p=0.003 ; table 3 ) . our study supports findings that serum fgf-23 levels are positively correlated with aorta abdominalis calcification . further , it shows that hfhd is more effective than lfhd in clearing serum fgf-23 and reducing aorta abdominalis calcification . moreover , multiple - regression analysis shows that advanced age , serum fgf-23 , and blood phosphorus are risk factors for the development of vascular calcification . fgf-23 is a mineral regulatory factor that regulates phosphate homeostasis in chronic kidney disease patients . fgf-23 decreases renal phosphate reabsorption and increases urinary phosphate waste by decreasing the expression of sodium - phosphate transporter in proximal tubular epithelial cells . compromised renal function may result in the accumulation of phosphorus and decreased clearance of blood fgf-23 levels . previous studies show that increased fgf-23 levels are correlated with increased mortality and vascular calcification in hemodialysis patient , which is supported by the results presented here . molecular weight cut - offs of traditional hemodialysis membranes range from 20 to 30 kda . thus , fgf-23 is not removed since it has a molecular weight of 32 kda . though we detected a small fluctuation of fgf-23 levels in the lfhd group , significant increases were not observed in our study . torres et al . ( 2008 ) found that lfhd treatment did not decrease serum fgf-23 concentration . in contrast , it has been shown that alpha1-microglobulin , which has a molecular weight of 33 kda , is reduced by 21% using a high flux polyether - sulfone membrane . another study found that the fgf-23 clearance rate by hfhd reaches to 36.228.6% , which is substantially lower than on - line hemodiafiltration , which has a fgf-23 clearance rate of 55.725.2% ) . in the present study , the clearance rate of fgf-23 in the hfhd group was 41.423.4% after 12 months of treatment , while fgf-23 increased 0.326.4% in the lfhd group . interestingly , we found that aorta abdominalis calcification is better controlled by hfhd than lfhd . further , we find that advanced age , blood phosphorus levels , and serum fgf-23 levels are all independent risk factors for the development of vascular calcification , which agrees with a previous study . another study , including 1130 healthy males , also suggests that circulating fgf-23 is associated with mineral metabolism , including bone metabolism - regulating cytokines , and with severe aacs independent of traditional risk factors . ( 2009 ) report that higher serum fgf-23 levels , even within normal range , are independently correlated with increased arterial stiffness and impaired vasoreactivity . these elevated fgf-23 concentrations may then stimulate vascular calcification by acting directly on the vascular wall to induce a local reduction of the enzyme klotho . interestingly , a recent study indicates that hemodiafiltration appears to offer no extra benefit over hfhd in terms of controlling vascular stiffness . this may due to the limited follow - up period or that the efficacies of hemodiafiltration and hfhd are similar in controlling vascular calcification . here , we show that the improvement of aacs in hfhd compared to lfhd is not significant at 6 months , but becomes significant at 12 months ( p=0.002 ) . first , the reliability of the study may be impaired by the small cohort size and short follow - up time . second , in 2009 , kdigo ( kidney disease : improving global outcomes ) guidelines suggested that an echocardiogram should also be used to detect the valvular calcification in esrd patients . hfhd is superior to lfhd and benefits hemodialysis patients by reducing serum fgf-23 levels and reducing vascular calcification .
backgroundhigh- and low - flux hemodialysis ( hfhd and lfhd , respectively ) are dialysis procedures designed to eliminate blood toxins that accumulate in end - stage renal disease . 
 hfhd may reduce vascular calcification by removing serum fibroblast growth factor 23 ( fgf-23 ) . however , whether hfhd is better than lfhd is still under debate . 
 we therefore compared the efficacy of hfhd and lfhd in controlling fgf-23 and vascular calcification.material/methodsfifty hemodialysis patients were recruited and randomly treated with either hfhd or lfhd . 
 fasting venous blood was collected at baseline , six months , and twelve months after the treatment . 
 we then measured levels of fgf-23 , calcium , phosphorus , parathyroid hormone , and alkaline phosphatase . 
 further , abdominal lateral radiographs were taken to calculate aorta abdominalis calcification scores ( aacs).resultscompared to the lfhd group , fgf-23 and aacs in the hfhd group significantly decreased after 12 months treatment ( p=0.049 and p=0.002 , respectively ) . 
 aacs were positively correlated with fgf-23 in all patients ( p=0.004 ) , the hfhd group alone ( p=0.040 ) , and the lfhd group alone ( p=0.037 ) . 
 we also found that older patients , patients with higher blood phosphorus levels , and higher fgf-23 levels had an increased risk of aorta abdominalis calcification ( p=0.048 , p=0.003 , p=0.001 , respectively ) . 
 hfhd was more able to reduce the risk of aorta abdominalis calcification than lfhd ( p=0.003).conclusionsfgf-23 is an independent risk factor for the development of vascular calcification . 
 hfhd may benefit hemodialysis patients by reducing serum fgf-23 levels and controlling vascular calcification .