Transmembrane pressure modulation in high-volume mixed hemodiafiltration to optimize efficiency and minimize protein loss

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1 & 26 Interntionl Society of Nephrology originl rticle Trnsmemrne pressure modultion in high-volume mixed hemodifiltrtion to optimize efficiency nd minimize protein loss LA Pedrini 1, G Cozzi 1, P Frnn 1, A Mercieri 1, P Ruggiero 1, S Zeri 1, A Felicini 1 nd A Riv 1 1 Nephrology nd Dilysis Deprtment, Bolognini Hospitl of Serite, Bergmo, Itly The im of the present study ws trnsmemrne pressure (TMP) modultion in high-volume mixed hemodifiltrtion (HDF) to optimize efficiency nd minimize protein loss. The optiml flow/pressure conditions in on-line mixed HDF ssisted with feedck control of TMP were defined in this prospective rndomized study in order to otin mximl efficiency in solute removl while minimizing potentil side effects. Two different TMP profiles in mixed HDF were compred in 12 unselected ptients who underwent two study periods of 2 weeks ech in cross-over rndomized sequence: (A) constnt TMP t round 3 mmhg nd (B) profiled TMP, in which TMP ws slowly incresed from low initil vlue to the mximl vlue. In oth procedures, the men volume exchnge ws l/h. Men filtrtion frction ws 53%. Instntneous 2-microgloulin (2-m) clernce ws higher t the strt of the session with profiled TMP (27735 vs ml/min, Po.5), wheres no differences were found t the end ( vs ml/ min). Profiled TMP resulted in higher men 2-m clernce of the session ( vs ml/min, Po.1), in lower lumin loss in the first 3 min ( vs g, Po.1), nd, in the whole session ( vs g, Po.1), in higher dilyzer ultrfiltrtion coefficients nd lower resistnce indexes. This study showed tht the TMP feedck modultion in mixed HDF ws highly effective in mintining very high ultrfiltrtion rtes nd filtrtion frctions, nd minimized potentil side effects s result of the improved preservtion of memrne permeility nd more fvorle dilyzer pressure regimen. Kidney Interntionl (26) 69, doi:1.138/sj.ki.11; pulished online 6 Jnury 26 KEYWORDS: hemodifiltrtion; convection; 2-microgloulin trnsmemrne pressure; feedck; middle molecule; profiling Correspondence: LA Pedrini, Nephrology nd Dilysis Deprtment, Bolognini Hospitl of Serite, Vi Pderno 21, Serite, Bergmo 2468, Itly. E-mil: nefrologi.serite@olognini.g.it or lxpedrini@hotmil.com Received 16 April 25; revised 2 Octoer 25; ccepted 6 Octoer 25; pulished online 6 Jnury 26 Convincing evidence exists tht hemodifiltrtion (HDF), compred to stndrd hemodilysis techniques, including high-flux hemodilysis, helps to remove lrger mount of middle moleculr compounds, 1 9 which hve pthogenic role or re mrkers of the most frequent long-term complictions nd cuses of deth in hemodilysis ptients, such s dilysis-relted myloidosis, crdiovsculr disese, inflmmtion, nd mlnutrition. Anemi nd iperphosphtemi lso seem to e etter controlled with HDF Indeed, solute removl otined y coupling diffusion nd convection in HDF is definitely higher thn tht ttinle y internl filtrtion in high-flux hemodilysis, provided tht the pplied ultrfiltrtion rte is high enough to properly exploit the high permeility of synthetic memrnes. Besides low ultrfiltrtion rtes, clinicl results of the technique my lso e vrily ffected y the infusion mode. Indeed, during the postdilution mode, hemoconcentrtion, nd high trnsmemrne pressure (TMP) cn cuse frequent clinicl nd technicl prolems, nd compromise the efficiency of the technique. On the other hnd, the predilution mode, while prtilly preventing these drwcks, reduces the cumultive solute trnsfer s consequence of the diluted solute concentrtion ville for diffusion nd convection Recently, we demonstrted tht mixed HDF (simultneous pre- nd postdilution), compred to the more trditionl infusion modes in HDF, is le to ensure sfer rheologicl nd operting conditions 15 nd to produce significnt gin in efficiency when incresing infusion rtes re pplied nd filtrtion is forced. 7 The operting conditions necessry to chieve these results were mintined through the use of new feedck system, designed in our deprtment, which is le to control the filtrtion pressure nd keep the ultrfiltrtion rte t the highest sfe rnge during the session y djusting the pre-/ post-filter infusion rtio ccording to the ptient nd dilyzer chrcteristics. 7 However, some concern rose from the oservtion tht consistent lumin loss, to such degree s to compromise the nutritionl sttus of the ptients, my occur during HDF, minly t the eginning of session s n effect of the high filtrtion pressure pplied to the intct memrne. 2 Kidney Interntionl (26) 69,

2 originl rticle LA Pedrini et l.: TMP modultion in mixed HDF In the light of this, our present ttempt ws to define the optiml flow/pressure conditions, which re needed in mixed HDF to est preserve the permeility properties of synthetic memrnes, in order to fully exploit their trnsport potentil nd otin mximl efficiency while minimizing potentil side effects, prticulrly protein loss. Different profiles of TMP were pplied with the id of the TMP feedck device nd solute removl, frctionl lumin loss, nd hydrulic permeility of the memrne were monitored nd compred t vrious times throughout the session. RESULTS Bseline ptient prmeters of the two experimentl periods (Tle 1) did not differ significntly. The men TMP (TMPm) profiles otined in the two study periods A nd B, in line with the study protocol, re depicted in Figure 1, with the men infusion rtes t the pre- nd postdilution site of the dilyzer, nd their chnges during the procedures, which were mnged y the feedck mechnism in order to mintin the progrmed TMP profile (see lso Tle 2). The totl infusion (pre þ postdilution) nd ultrfiltrtion rtes of the sessions were similr in oth procedures (Q S, ml/ min; Q UF, ml/min). In procedure B, compred with procedure A, lower TMP vlues, corresponding to the plnned profile, were mintined t the strt of the session with higher infusion rte given in predilution. Nevertheless, t the end of the sessions, the mount of fluid infused in postdilution ws similr for the two procedures, s result of the repeted shifts of replcement fluid driven y the device lgorithm. The filtrtion frction ws lower t the strt of session B (Tle 2), s consequence of the higher rte of predilution infusion, ut s men, very high filtrtion frction (FF) were mintined during the sessions of oth study periods, ensuring tht the highest possile convective flux hd een chieved. Tle 1 Bseline nd end-session ptient prmeters Constnt TMP Profiled TMP P-vlue* Ure (mmol/l) Strt NS End NS 2-m (mg/l) Strt NS End NS Hemtocrit (%) Strt NS End NS Totl protein (g/l) Strt NS End NS Alumin (g/l) Strt NS NS: not significnt. Dt re mens7s.d. *Student s t-test for pired dt. Efficiency of the procedures nd dilyzer performnce No difference ws oserved etween the two TMP profiles in ure K DQ nd ek t /V (Tle 3). Instntneous 2-microgloulin (2-m) dilyzer clernces (K 2-m ), clculted to test the dilyzer performnce in terms of 2-m removl nd its chnges over time in dilysis (Figure 2), were significntly higher in procedure B t the strt of the sessions (27735 vs ml/min, Po.5), wheres no difference ws found etween the two procedures t the end of the session ( vs ml/min). However, significnt decline in 2-m K from the strt to the end (more thn 3% of the initil vlue) ws recorded with oth procedures. The efficiency in removing middle-sized solutes, clculted from the mount of 2-m recovered in the totl spent dilyste (MT DQ ) nd the men 2-m whole-ody clernce (K DQ ), ws significntly higher in session B, performed under TMP modultion (Tle 3) thn in session A. Together with methodologicl resons implicit in the DQ method, 21 solute sorption on the memrne my explin why 2-m K DQ vlues (clculted from the dilyste side) were significntly lower thn the instntneous K 2-m vlues (clculted from the lood side), nd underestimted the ctul dilyzer clernce. TMP (mmhg) TMP (mmhg) Figure 1 TMPm profiles (line ) with 95% CI of the 144 experimentl procedures nd, otined y djusting the pre/postdilution infusion rtio under TMP feedck control. At the strt of the session, smll shifts of infusion fluid from predilution (line c) to postdilution (line ) incresed the filtrtion frction nd stilized TMP within close opertionl rnge round its mximl vlue (3 mmhg). () This ws chieved rpidly or () grdully over 3 min, ccording to the study protocol. Susequently, during the session, TMP vlues tht exceeded the upper limit were reduced y shifts of infusion fluid in the opposite direction. c c 1 1 Q s, (ml/min) Q s, (ml/min) 574 Kidney Interntionl (26) 69,

3 LA Pedrini et l.: TMP modultion in mixed HDF originl rticle Tle 2 Flow rtes during the experimentl procedures Constnt TMP Profiled TMP P-vlue* Q Beff (ml/min) NS Q PW (ml/min) Strt NS End NS Q Spre-D (ml/min) Strt o.1 End NS Q Spost-D (ml/min) Strt o.1 End NS Q UF (ml/min) Men NS Filtrtion frction (%) Strt o.5 End NS Men NS Arevitions nd definition of the prmeters re in the text (section Mterils nd Methods). The filtrtion frction ws clculted with eqution (2). Dt re mens7s.d. *Student s t-test for pired dt. Tle 3 Efficiency of the experimentl procedures Constnt TMP Profiled TMP P-vlue* K DQ Ure (ml/min) NS ek t /V NS 2-m MT (mg/session) o.5 2-m K DQ (ml/min) o.1 Arevitions nd definition of the prmeters re in the text (section Mterils nd Methods). Dt re mens7s.d. *Student s t-test for pired dt. K β2-m (ml/min) Strt session End session Figure 2 Instntneous 2-m clernce t the strt nd the end of the experimentl procedures A (shded columns) nd B (drk columns), evluted from the lood side. Pired Student s t-test: () profiled vs constnt TMP, Po.5 nd () strt vs end session, Po.1. Tle 4 Alumin loss during the experimentl procedures Constnt TMP Profiled TMP P-vlue Mss in dilyste (g) Strt 3 min o.1 3 min end o.5 Totl o.1 Rte of loss (mg/min) Strt 3 min o.1 3 min end o.1 Totl o.1 Dt re mens7s.d. Student s t-test for pired dt. Profiled vs constnt TMP sessions. Strt 3 min vs 3 min end periods. The men mount of lumin detected in the frctionl dilyste collection in the first 3 min nd in the spent dilyste of the whole sessions ws significntly lower in procedure B (Tle 4). In session A, conducted with constnt TMP, the rte of lumin lekge ws significntly higher in the first 3 min thn in the rest of the sessions ( vs mg/min, Po.1), wheres no differences were found t the different times in session B. Effects on dilyzer permeility The ehvior of the in vivo ultrfiltrtion coefficients (K UF D, ml/h/mmhg of TMP) nd of the resistnce index (R I ¼ P Bin / Q Bin ) of the dilyzers during the sessions (Figures 3 nd 4) indicted rpid deteriortion of the hydrulic memrne permeility, which occurred mostly during the first hlf hour in oth procedures, owing to protein lyer formtion nd its progressive thickening. The phenomenon ws similr for the three employed dilyzers, ut it ws generlly much more prominent in procedure A, in which K UF D ws reduced in the first few minutes of the sessions. In ll cses, only fter out 35 min into the session did the K UF D vlues of the two procedures overlp nd it remined constnt fter tht. Slowly incresing TMP ccording to the plnned profile in procedure B seemed to ensure etter preservtion of the hydrulic memrne chrcteristics nd provides lower risk pressure regimen inside the dilyzer. DISCUSSION When lood strts flowing within the dilyzer nd first comes into contct with the memrne, protein mteril is ttrcted to nd dheres to the memrne surfce (fouling phenomenon). At low ultrfiltrtion rte, only smll peptides nd proteins re trpped y the memrne pores nd dhere to their inner surfce. Compred to the intct memrne, this nrrowing of the pore size leds to lrger plsm molecules, such s lumin, eing rejected, wheres permeility to solutes in the middle moleculr rnge, such s 2-m, is not sustntilly modified. When higher ultrfiltrtion rte is pplied, protein polriztion on the inner memrne surfce Kidney Interntionl (26) 69,

4 originl rticle LA Pedrini et l.: TMP modultion in mixed HDF K UF D (ml/h/mmhg) TMP K UF D (ml/h/mmhg) TMP K UF D (ml/h/mmhg) TMP c Figure 3 (, HF8S;, FX8; c, FX) Behvior of the pprent ultrfiltrtion coefficient of the dilyzers (K UF D ¼ Q UF /TMP) s men of the on-line records otined during the experimentl procedures. The chrcteristics of the dilyzers re descried in the text (section Mterils nd Methods). Lines, constnt TMP sessions; lines, profiled TMP sessions. RI Figure 4 Behvior of the resistnce index (R I ¼ P Bin /Q Bin ), s recorded on-line for the dilyzer FX during the experimentl procedures line nd line. The trend of R I for the other dilyzers (HF8S nd FX8, not shown) is very similr nd overlps to tht depicted here. lso tkes plce, nd the thickness of the secondry protein lyer is proportionl to the filtrtion pressure. Under these conditions, even lrger proteins my e pushed into nd entrpped inside the pores, with the effect of permnent nd significnt reduction of memrne permeility. 22 Protein lekge is n effect of using high-flux memrnes in convective therpies, which provokes concern, owing to its negtive influence on the nutritionl sttus of the ptients. 17,18 High-flux memrnes, hving generlly cutoff up to 2 D, my e responsile for mssive protein lekge minly in the erly phse of the session, when high filtrtion pressure is pplied to the intct memrne nd even lrge molecules such s lumin my e forced into nd cross the intct pores. Kim et l. 2 showed tht it ws possile to reduce this negtive effect y voiding ggressive filtrtion in the erly phse of n HDF session. Two profiled filtrtion modes, plnned to reduce the initil filtrtion to lower level, resulted in miniml lumin loss nd higher 2-m removl thn tht in the conventionl constnt flow or pressure technique. However, in Kim s study, low flow/pressure profile in the first prt of the session nd TMP control could only e otined y reducing the totl exchnge volume, with the effect of lso reducing the efficiency of the technique. Moreover, this experience ws only conducted in predilution HDF, where etter rheologicl conditions occur compred to postdilution. On the other hnd, postdilution, commonly held s the most efficient infusion mode in HDF, implies clinicl nd technicl risks in its ppliction. In fct, when high ultrfiltrtion rtes re pplied, lood viscosity nd resistnce to flow increse, nd progressive protein concentrtion contriutes to thickening of the secondry memrne lyer, hence limiting its hydrulic nd solute permeility. Excessive hemoconcentrtion ffects trnsmemrne solute trnsfer nd is likely to cuse fier nd dilyzer clotting, nd the high pressure required to yield the plnned filtrte flow my cuse red cell dmge nd protein denturtion, stretching nd rupture of the memrne, nd deformtion of its pores, through which mssive protein lekge my occur. Even if n increse in UF flux through high-flux polysulfone memrne ws oserved with intrvenous infusion of hypertonic glucose during postdilution HDF, 23 the events descried ove re difficult to counterct y using the ultrfiltrtion control systems employed on currently ville HDF mchines, s these re of little or no help in plnning nd crrying out session in which ultrfiltrtion flow or pressure is profiled, or incresingly higher nd unpredictle TMP grdients re utomticlly prevented in order to mintin sfe opertionl conditions. Previous studies hve shown tht limits nd risks implicit in the trditionl infusion modes in HDF my e overcome with on-line mixed HDF, which ensures more fvorle lood rheology nd memrne permeility thn in the postdilution mode, nd llows the totl infusion to e incresed nd convective removl to e forced eyond the opertionl limits plced in postdilution. In mixed HDF, this incresed mount of infusion is dded in predilution nd 576 Kidney Interntionl (26) 69,

5 LA Pedrini et l.: TMP modultion in mixed HDF originl rticle lnced with tht in postdilution in order to ensure the highest possile filtrtion frction, while simultneously voiding dngerous hydrosttic pressures within the dilyzer nd excessive dilution of the inlet solute concentrtions. The very high ultrfiltrtion rte resulted in significnt increse in 2-m removl compred to tht otined with the postdilution mode. This ws fesile in sfe wy only y using the feedck device for TMP control developed in our unit. The device ws le to regulte the TMPm t its highest sfe vlue y mens of smll shifts (5 1 ml) of sustitution fluid from the postdilution to the predilution infusion site or vice vers, thus reducing or incresing, respectively, the filtrtion frction, without reducing the plnned ultrfiltrtion rte. 7 In the present study, the creful control of TMP, which ws never permitted to rech dngerous vlues, llowed protein loss to e contined within cceptle limits, lso using constntly high TMP vlues s in procedure A. However, in greement with the findings of Kim s study, protein lekge ws further reduced y pplying low filtrtion pressure t the eginning of the session nd grdully incresing it to rech the plnned vlue fter the first hlf hour of the session. This ws otined with the help of the TMP feedck in mixed HDF without reducing the totl ultrfiltrtion rte, ut only with utomtic shifts of smll mounts of the infusion fluid from the postdilution to the predilution port of the dilyzer. As finl result, the cumultive lumin loss of the sessions ws significntly lower in those sessions in which TMP ws modulted s ove. In ddition, profiled TMP pplied during mixed HDF etter preserved the hydrulic nd solute permeility of the memrne, s demonstrted y the higher vlues of the dilyzer ultrfiltrtion coefficient nd 2-m clernce mesured in the first prt of the profiled TMP sessions compred to those with constnt high filtrtion pressure. This resulted in significntly incresed cumultive 2-m removl. MATERIALS AND METHODS This prospective, rndomized, cross-over study ws pproved y the locl Ethics Committee. Twelve uremic ptients (three femle nd nine mle, ged yers), who were on three times weekly renl replcement therpy, six with HDF for yers nd six with high-flux hemodilysis for yers, gve their informed consent to the study. The men ody weight ws kg nd the men kineticlly estimted ure distriution volume (V u ) ws l. All the ptients underwent two study periods of 2 weeks ech with mixed HDF. The sequence of the two study periods ws rndomly ssigned to the ptients. In the first period (period A), TMP ws mintined from the strt of the sessions within strict rnge of vlues round the highest sfe vlue (B3 mmhg), wheres in the second period (period B), modulted TMP profile ws pplied, in which TMP ws grdully incresed over out 3 min from low initil vlues up to the highest. These were then kept constnt throughout the rest of the session, s shown in Figure 1. A totl of 144 sessions were studied. The sme high-flux polysulfone dilyzer in routine use for ech ptient ws used in oth study periods (FX 8 in four ptients, FX in four nd HDF s in four; ll dilyzers re produced y Fresenius, FMC, Bd Homurg, Germny). The length of the session (t, min) nd the lood flow rte (Q B, ml/min) were kept constnt for ech ptient for ech session in the study. The effective lood flow Q B eff (i.e. the vlue for Q B corrected for the negtive pressure of the rteril line efore the pump nd its inner dimeter) ws ml/min. The inlet dilyste flow (Q D ) ws ml/min. Access flow recircultion, tested in previous routine sessions, ws lwys less thn 1%. Anticogultion ws performed with unfrctionted heprin with the sme regimen in ll experimentl sessions (initil olus IU/kg, continuous infusion of IU/h). The TMP feedck control On-line mixed HDF ws performed with new dilysis mchine (Fresenius 8, Fresenius, FMC, Bd Homurg, Germny), equipped with two peristltic pumps for simultneous pre- nd postfilter infusion, nd feedck system for TMP control, which ws further development of similr device previously vlidted on Fresenius 48 mchine. 7 The system opertes t the strt of the session y setting the totl infusion rte (Q S, ml/min) ccording to the plsm wter flow rte of the ptient (Q PW, ml/min) nd the rtio etween pre- nd postinfusion rtes (Q Spre /Q Spost ) ccording to the desired FF. Q PW is clculted from Q Beff, hemtocrit (Hct) nd the wter frction of plsm (F p ) with the clssic eqution: 24 Q PW ¼ Q B eff ð1 Hct=ÞF p ð1þ FF is defined ritrrily s the frction of Q PW ultrfiltered during the pssge through the dilyzer, in nlogy with more strict definition: 25 FF ¼ð1 Q PW out =Q PW in Þ¼Q UF =Q PW in ð2þ where Q UF equls the totl ultrfiltrtion rte (Q S plus the rte of ody weight decrese, in ml/min), Q PW in is the plsm wter flow rte entering the dilyzer tht, s here in the cse of mixed pre- nd postinfusion, equls the plsm wter flow rte of the ptient (Q PW ) dded to the preinfusion rte (Q Spre ): Q PW in ¼ Q PW þ Q Spre nd Q PWout is the outlet plsm wter flow rte: Q PW out ¼ Q PW in Q UF Different options re ville oth for Q S s function of Q PW in (Q S /Q PW in from.6 to 1.), nd for FF from.3 to.5 in steps of.5. In this study, men individul rtio Q S /Q PW in of.7 (rnge.6.8) nd n initil FF of B.5 were set on the sis of previous experience 7 nd the results of pilot sessions in which different infusion flow distriutions (nd FF) were tested to otin the desired TMP profile in ech ptient. The split etween pre- nd postinfusion rte (ml/min) ws computed y the softwre device ccording to the set FF nd the following equtions, derived from equtions (2) nd (3): nd, Q Spre ¼ðQ UF FF Q PW Þ=FF Q Spost ¼ Q S Q Spre ð6þ After the initil setting, s descried elsewhere, 7,26 the mchine strts to record rel-time vlues for the pressures t the inlet nd outlet ð3þ ð4þ ð5þ Kidney Interntionl (26) 69,

6 originl rticle LA Pedrini et l.: TMP modultion in mixed HDF lood nd dilyste ports (P Bin, P B out, P Din, P D out, respectively, mmhg) y mens of four pressure trnsducers connected to n externl computer, nd the men TMP within the dilyzer (TMPm, mmhg) is clculted instntneously using the following eqution: TMPm ¼:5ððP Bin þ P B out Þ ð7þ ðp Din þ P D out ÞÞ p where p (mmhg) is the men oncotic pressure exerted y the plsm proteins, set y defult to constnt vlue of 25 mmhg. Susequently, the feedck cts to mintin TMPm vlues within the progrmed rnge, which cn e constnt, s in the experimentl period A, or vrily profiled, s in period B. This tsk is ccomplished y djusting the rtio of pre- to postinfusion, nd thus FF, without chnging the totl Q UF : smll mount of fluid (5 1 ml/ min) is diverted from pre- to postinfusion if TMPm drops elow the estlished lowest limit or, vice vers, from post- to predilution, whenever TMPm rises eyond its mximum tolerted vlue (3 mmhg). The net effect is, respectively, to increse or decrese FF nd thus to mintin the highest filtrtion pressure comptile with the increse in hemoconcentrtion nd loss of hydrulic memrne permeility, which occurs s the session progresses. The mchine softwre recorded nd computed signls le to monitor the pressure drop within the dilyzer, the resistnce index (R I ¼ P Bin /Q Bin ) nd the vlues for the in vivo ultrfiltrtion coefficients (K UF D, ml/h/mmhg of TMP) of the dilyzers, which were used s proxy to evlute chnges in the hydrulic permeility of the dilyzer during the sessions. Solute removl The mid-week session of the second week of ech experimentl period ws chosen to test the efficiency of the tretments. The men efficiency of ech session ws evluted using the prtil dilyste quntifiction (DQ) method. 27 The effluent dilyste, collected t constnt rte over the session with proportionl pump, ws processed for ure, 2-m, nd lumin concentrtion (C d ). Seprte dilyste collection of the first hlf hour ws performed for lumin loss quntifiction. Blood smples were drwn from the rteril port t the strt nd t the end (slow-flux technique) of the sessions nd plsm concentrtions (C i, C f ) were mesured for ure (6 kd) nd 2-m (11.8 kd), tken s mrkers of the low nd medium-high moleculr weight toxins, respectively. The mss of solute removed during ech session (MT DQ ) ws clculted from the effluent dilyste smple (B ml), representtive of the whole spent dilyste (V d ), s in: MT DQ ¼ C d V d ð8þ The following eqution of the DQ method ws used to clculte the men dilyste clernces of the session K DQ : 27 K DQ ¼½MT DQ lnðc f =C i ÞŠ=½tðC f C i ÞŠ ð9þ Clculted s ove, MT DQ nd K DQ underestimte the ctul 2-m removl, ecuse of the mount of solute sored on the memrne nd not detectle in dilyste collection. However, this systemtic nd constnt error is unlikely to ffect the results of comprison etween the different procedures in the sme ptient nd with the sme dilyzer. The equilirted K t /V (ek t /V) for ure ws estimted from ure K DQ nd V u, nd the session time (t). Dilyzer performnce in MM removl t different times of the session ws evluted y clculting 2-m instntneous dilyzer clernces (K 2-m ) 5 min fter the strt nd efore the end of the session. For this purpose, lood smples were drwn simultneously from the inlet nd outlet lood port of the dilyzer, nd plsm wter 2-m concentrtion (C rt, C ven ), hemtocrit nd totl plsm protein (TP) concentrtion were mesured. The clssic eqution for the solute mss trnsport ws pplied to clculte K: 24 K 2m ¼ Q PW ðc rt C ven Þ=C rt þ Q UF C ven =C rt ð1þ Immunonephelometry ws used to mesure 2-m nd lumin in oth plsm nd dilyste. Sttisticl nlysis The descriptive nlysis ws sed on the men7s.d. vlues of continuous normlly distriuted vriles. The effects of the two procedures on prmeters of tretment efficiency (K DQ, ure K t /V, nd MT DQ ) were compred with the Student s t-test for pired dt. A proility vlue of less thn.5 ws considered significnt. CONCLUSIONS Mixed HDF hs lredy een shown to e highly effective technique to remove uremic solutes of middle moleculr weight, while voiding the known drwcks of the trditionl infusion modes. The ppliction of the TMP feedck control system, which modultes the filtrtion pressure in order to preserve the hydrulic nd solute permeility of the memrne, further incresed the efficiency of the technique nd minimized lumin lekge. The high iocomptiility resulting from the use of synthetic memrnes nd ultrpure dilyste/sustitute prepred online with doule ultrfiltrtion, comined with the enhnced removl of smll nd middle moleculr uremic toxins, seems to indicte tht TMP-modulted mixed HDF is n effective strtegy to prevent or dely the occurrence of long-term dilysis complictions nd to promote improved survivl of dilysis ptients. ACKNOWLEDGMENTS This work hs een ccepted s free communiction t the XXXXII ERA-EDTA Congress in Istnul, Turkey, 25, nd t the 3rd World Congress of Nephrology, Singpore, 25. REFERENCES 1. Boumn CS, Vn Olden RW, Stouteneek CP. Cytokine filtrtion nd dsorption during pre- nd postdilution hemofiltrtion in four different memrnes. Blood Purif 1998; 16: Goldfr S, Golper TA. Proinflmmtory cytokines nd hemofiltrtion memrnes. J Am Soc Nephrol 1994; 5: Kiser JP, Oppermnn M, Gotze O et l. Significnt reduction of fctor D nd immunosuppressive complement frgment B y hemofiltrtion. 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