continuous renal replacement therapies ( crrt ) have changed substantially the last two decades . developed as a practical method to treated acute kidney failure in unstable patients and based in the use of convection , in the first stages a low solute clearance capability was characteristic and subsequent changes ( as an early shift from an arterial - vena to a vena - vena approach )   were aimed to improve performance . to raise the clearance of uremic toxins , crrt procedures evolved to slightly different methods like continuous hemodiafiltration ( chdf )   or continuous hemodialysis ( chd )   because a supplementary diffusive transport can improve the clearance of low molecular weight toxins , such as urea .  
dosage delivered as convective treatment can theoretically be raised without limits but in the real practice we have a limiting factor , that is , blood flow .
when this limit has been reached to augment the dialysate flow seems an attractive alternative but some early reports demonstrated that when we set the dialysate over 25  ml / min , efficiency of the treatment is seriously compromised and this effect is related to the membrane involved . in our unit ,
the weaning from crrt is usually performed with slow intermittent dialysis delivered with the same crrt monitor , in sessions lasting 1012 hours . during this weaning phase
some patients require a dose of dialysis theoretically surpassing the capability of the an609 membrane .
we designed this study to detect whether high dose dialysis performed with a membrane of low diffusive capability ( an69 ) was able to fulfill efficiently the requirements for our patients .
our objective was to determine if a higher dose of dialysis could be delivered efficiently with this membrane .
we conducted a prospective observational study , collecting data from 10  icu patients with acute kidney injury managed with chdf .
chdf is conducted in our unit with a prismaflex monitor ( hospal ) and a 1.4  m an69 membrane filter ( hf-1400 , hospal ) .
bicarbonate buffered fluid is infused in postdilution mode and the anticoagulant regime is adjusted to the clinical condition of the patient , using three alternatives : nonfractionated heparin at 5  u / kg / h , epoprostenol at 5  ngr / kg / min , or no anticoagulation .
initial prescribed dose is 35  ml / kg / h , with the convective component as high as possible ( according to catheter performance and keeping filtration fraction below 20% ) ; when the complete dose can not be achieved the rest is delivered as dialysis . when the patient is hemodynamic stable the dose is lowered , aiming for internal milieu normality , and usually convective and diffusive components
finally , the weaning process is performed with slow intermittent dialysis delivered with the prismaflex monitor in sessions lasting 1012 hours every day . during the weaning phase of the treatments some patients require a dose of dialysis theoretically surpassing the capability of the an609 membrane .
so we designed this protocol to assure that an efficient treatment was delivered . every day and during the morning shift , treatment prescription was changed temporarily to a blood flow ( qb ) of 250  ml / min , a dialysate flow rate ( qd ) of 50  ml / min ( 3  l / h ) , and zero ultrafiltration / zero negative balance ; anticoagulation was maintained without changes .
the monitor was kept running for 15 minutes before samples were taken and then was immediately reverted to the original prescription for each patient .
transmembrane pressure ( tmp ) and anticoagulation regime at this time were registered for each measure .
blood samples were taken pre- and postfilter using the ports in the circuit and a sample of the effluent was extracted from the port in the effluent line .
samples were transferred immediately to the laboratory for determination of urea , creatinine , and 2-microglobulin .
saturation of the dialysate was calculated using the equation:(1)saturation=  ( [ ef]([in]+[ou])/2 ) , 
 where [ ef ] is the concentration of a solute in the effluent , [ in ] is the concentration in the before filter blood sample , and [ ou ] is the concentration in the after filter sample .   data are shown as mean ( standard deviation ) or n ( percentage ) . to test hypothesis we used u mann - whitney or kruskal - wallis , and for the study of the relationship between continuous variables a linear regression analysis was performed .
we performed 44 measurements in 10 patients , with a median of 3 measures / patient ( in 3 patients 1 measure and in one 16 measures ) .
all patients were treated with bicarbonate buffered hemodiafiltration with a mean qb of 241  37.1  ml / min and a mean dose ( qd ) of 2506    69  ml / h .
mean tmp at the moment of the measurement was 81  60  mmhg and the anticoagulant regime employed at this point was heparin in 18 ( 40.9% ) , epoprostenol in 9 ( 20.5% ) , and none in 17 ( 38.6% ) measures .  
mean saturation of dialysate was 1.08  0.09 for urea and 0.86  0.22 for creatinine ( p < 0.001 ) , and the relationship between both measures showed a wide distribution of data ( figure 1 ) .
we detected a decrement of 2-microglobulin in relation to filters running time ( r = 0.15 , p < 0.05 ) and not for urea or creatinine but , while urea saturation was close to 1 without evident changes in time , creatinine saturation showed an erratic behavior with a wide dispersion of data ( figure 2 ) . a fall in dialysate saturation following an increment of tmp was observed for the three molecules , more marked for 2-microglobulin than urea or creatinine and once more with a wide dispersion for the last one ( figure 3 ) .
the best dose is an open debate [ 710 ] but in practice is markedly higher than two decades ago .
other aspect under debate is whether this dose must be delivered as convection , diffusion , or both but the most widely employed modality is mixed chdf [ 1113 ] . when prescribing crrt , synthetic membranes with low diffusive performance are employed and a raise in the dialysate flow rate will not be always followed by a proportional increment in dose . as a general rule , keeping dialysate flow rate below 2530 
ml / min has been considered adequate [ 14 , 15 ] but our results demonstrate that with a 1.4  m an69 membrane this threshold can be raised up to 50  ml / min ( 3  l / h ) while keeping dialysate saturation in the optimal range . when prescribing crrt , high permeability synthetic membranes are used and some of these membranes show a low performance in diffusion .
the classical membrane requirement to be met with respect to diffusive clearance has been in the past the complete saturation of the dialysate at flow rates up to 30  ml / min   because beyond this boundary the ability to completely saturate the dialysate begins to fall .
this effect is potentially more significant when using polyamide compounds , which show low diffusive transport properties .
now we can confirm that a complete saturation of the dialysate should be expected with flows up to 50  ml / min ( 3  l / h ) ( nearing the dose achieved with other diffusive treatments like sledd ) [ 1820 ] .  
interrelation between convection and diffusion in the ultrafiltrate compartment of the filter is complex ( e.g. , it has been demonstrated that predilution infusion in high efficiency systems results in a drop in dialyzer clearance compared to dialysis alone ) .
we must assume that convection and diffusion do not simply add their effect but that a continuous interference between them is present .
we have not evaluated the role of a mixed therapy and purposefully have isolated the effect of diffusion to definitely characterize this , so our conclusions only apply for purely diffusive treatments ( continuous hemofiltration ) but not mixed modalities ( hemodiafiltration ) when some interaction should be expected . in these cases ,
when a high dialysate flow is prescribed , we think it is advisable to measure effluent saturation to ensure an adequate dialysis delivery .  
we have detected a significant difference in the urea and creatinine saturation ; while the first one behaved as a good marker for saturation ( all the data obtained from urea were consistent and narrowly distributed close to unity ) , creatinine showed a wide dispersion of data and is our conclusion that creatinine is not an adequate marker for dialysate saturation .
we have no explanation for this finding but in part could be reflecting a problem with the determination of creatinine ; our laboratory uses the jaffe technique , known to show variations ranging from 5.3 to 27.4  mol / l .
the first one lays in the fact that we did perform the measures in a  laboratory  setting by standardizing the modality and not analyzing the patients who were really being treated .
consequently our conclusions do not apply when a mixed ( convective - diffusive ) therapy is performed .
our main objective was to detect the capability of the membrane to deliver a high dose of dialysis so opted for the use of this modality alone , limiting possible confounding factors and assuming the lose of external validity of our results .
an other limiting factor is the material employed ; our results are only valid when chd is performed with a 1.4  m an69 membrane but , being this synthetic membrane the less efficient for diffusion , we believe that 50  ml / min can be considered a reasonable minimum for any other synthetic membrane employed in crrt .   even though the number of measures was adequate to perform the analysis , the number of patients recruited is small and did not let us introduce patient related factors that hypothetically could have altered our results ; so our conclusions must be understood as technically and not clinically oriented until more studies are published , but the similitude between our findings and those of ricci et al .   is encouraging and support our conclusions . we conclude that the an69 membrane shows a higher diffusive performance than previously reported , up to 50  ml / min , covering efficiently the range of standard dosage for continuous therapies .
 an69 membrane is not suited for diffusion , with an suggested limit at 25  ml / min dialysate flow rate . when prescribing continuous hemodialysis this threshold must be surpassed to achieve . 
 we designed a study aimed to check if a higher dose of dialysis could be delivered efficiently with this membrane . 
 ten icu patients under continuous hemodiafiltration with 1.4  m2 an69 membrane were included and once a day we set the monitor to exclusively 50  ml / min dialysate flow rate and 250  ml / min blood flow rate and after 15 minutes measured dialysate saturation for urea , creatinine , and 2-microglobulin . 
 we detected that urea saturation of dialysate was nearly complete ( 1.1  0.09 ) for at least 40 hours , while creatinine saturation showed a large dispersion ( 0.86  0.22 ) and did not detect any relation for these variables with time , blood flow , or anticoagulation regime . 
 saturation of 2-microglobulin was low ( 0.34  0.1 ) and decreased discretely with time ( r2 = 0.15 , p < 0.05 ) and significantly with tmp increases ( r2 = 0.31 , p < 0.01 ) . in our experience 
 an69 membrane shows a better diffusive capability than previously acknowledged , covering efficiently the range of standard dosage for continuous therapies . 
 creatinine is not a good marker of the membrane diffusive capability . 
1. Introduction
2. Methods
3. Results
4. Discussion