Association of Continuous-Equivalent Urea Clearances with Death Risk in Intermittent Hemodialysis

Resea ch A icle Associa ion o Con inuous-Equi alen U ea Clea ances wi h Dea h Risk in In e mi en Hemodialysis Aa ne Va ia,1Heini Huh ala,2and Jukka Mus onen3,4 1Sa onlinna Cen al Hospi al, 57120 Sa onlinna, Finland 2School o Heal h Sciences, Uni e si y o Tampe e, 33014 Tampe e, Finland 3School o Medicine, Uni e si y o Tampe e, 33014 Tampe e, Finland 4Tampe e Uni e si y Hospi al, 33521 Tampe e, Finland Co espondence should be add essed o Aa ne Va ia; aa ne. a [email protected] Recei ed 19 Janua y 2016; Accep ed 30 Ma ch 2016 Academic Edi o : Deepak Malho a Copy igh © 2016 Aa ne Va ia e al. This is an open access a icle dis ibu ed unde he C ea i e Commons A ibu ion License, which pe mi s un es ic ed use, dis ibu ion, and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed. Backg ound. Se e al epo s desc ibe a o able esul s om equen hemodialysis, bu due o he lack o unequi ocal dose measu es i is no clea whe he he bene i s a e due o mo e e icien oxin emo al o o he ac o s. Me hods.Theassocia ionswi hdea h isk o six con inuous-equi alen u ea clea ance measu es we e compa ed in 57 con en ional in-cen e hemodialysis ea men pe iods o 51 pa ien s, oge he 114 pa ien yea s. The double pool dose measu es we e calcula ed wi h he Solu e-Sol e p og am and sepa a ely scaled o u ea dis ibu ion olume o no malized wi h body su ace a ea. Resul s. Mo ali y associa ed signi ican ly wi h equi alen enal u ea clea ance (EKR) scaled o u ea dis ibu ion olume (𝑉)(𝑝 = 0.033)andwi hEKRno malizedwi h body su ace a ea (BSA) (𝑝 = 0.044)bu no wi h𝑉-scaled (𝑝 = 0.059) no BSA-no malized (𝑝 = 0.183) s anda d clea ance (s dK). Women had signi ican ly highe no malized p o ein ca abolic a e (nPCR), EKR/𝑉,ands dK/𝑉 han men bu sligh ly lowe BSA-no malized dose measu es and lowe mo ali y. P o ein ca abolic a e and dialysis dose co ela ed posi i ely wi h each o he and wi h su i al. Conclusions. The p ognos ically mos alid con inuous-equi alen clea ance in he p esen ma e ial was EKR/𝑉, calcula ed om double pool u ea gene a ion a e, dis ibu ion olume, and ime-a e aged concen a ion. 1. In oduc ion Su i al co ela es wi h u ea-based hemodialysis session dose in many la ge egis y s udies (Low ie e al. [1]: 43,334 pa ien s, Po e al. [2]: 84,936 pa ien s, and Mille e al. [3]: 88,153 pa ien s) in con en ional h ice-weekly schedule, bu in he andomizedcon olledHEMO ialmeanequilib a ed K𝑡/𝑉 (eK𝑡/𝑉) 1.53 did no esul in a signi ican ly be e ou come han 1.16 [4]. In e mi en hemodialysis ea men s can be compa ed o each o he by he session dose measu es URR, K𝑡,K𝑡/𝑉, and eK𝑡/𝑉 only i he ea men equency is equal. Se e al obse a ional s udies, e e ed o in [5, 6], and he andom- ized con olled FHN ial [7] desc ibe posi i e esul s om equen (“daily”) hemodialysis. Howe e , he ole o solu e emo al e iciency emains obscu e. U ea dis ibu ion olume (𝑉)isanessen ial a iable in kine ic modeling and can be used as a ep esen a i e o pa ien size, a scaling ac o . Howe e , i may ha e also an independen e ec on ou come [1, 8], which weakens he alue o K𝑡/𝑉 as a p ognos ic ac o . BSA has ecen ly been ecommended o scaling o dialysis dose simila ly as in exp essing he glome ula il a ion a e [9]. 𝑉-scaled dosing may esul in subop imal ou come in women and child en. Equi alen enal u ea clea ance (EKR, Casino and Lopez) [10] and s anda d clea ance (s dK, Go ch) [11, 12] ake ea men equency and esidual enal unc ion (RRF) in o accoun and hey we e in ended o use in compa ing dialysis doses in di e en schedules and o con inuous dialysis and enal unc ion [13, 14]. RRFmaycon ibu esigni ican ly o he o alweekly solu e emo al [14] bu only minimally (usually <1%) o he deli e ed K𝑡/𝑉o URR measu ed om blood samples. Renal clea ance (K ) can be added ma hema ically o session K𝑡/𝑉 [15–17]. Con inuous-equi alen clea ance based on UKM Hindawi Publishing Co po a ion Ad ances in Neph ology Volume 2016, A icle ID 9342853, 8 pages h p://dx.doi.o g/10.1155/2016/9342853 2Ad ances in Neph ology Table 1: Associa ion o pa ien cha ac e is ics and dialysis dose measu es wi h dea h isk in 57 hemodialysis ea men pe iods o 51 pa ien s. Mean SD Min Max Uni a ia e 𝑝OR 95% CI Age Yea s 61.6 15.5 16.7 91.6 0.103 1.038 0.993–1.085 Weigh kg 75.1 18.2 44.2 123.6 0.525 0.989 0.957–1.023 BMI kg/m226.1 5.5 16.3 43.7 0.198 0.924 0.819–1.042 BSA m21.84 0.25 1.31 2.34 0.872 0.823 0.078–8.727 𝑉L 31.8 6.7 20.5 50.3 0.637 1.021 0.936–1.113 nPCR g/kg/day 1.15 0.24 0.73 1.74 0.058 0.065 0.004–1.095 nK mL/min/1.73 m21.7 1.4 0.0 6.0 0.861 0.963 0.631–1.469 nEKR mL/min/1.73 m212.5 1.3 8.4 16.4 0.044 0.611 0.379–0.988 ns dK mL/min/1.73 m28.5 1.0 6.2 12.2 0.183 0.638 0.330–1.235 nEKRan mL/min/1.73 m215.1 2.3 8.3 20.3 0.113 0.806 0.617–1.053 ns dKan mL/min/1.73 m210.2 1.6 6.1 14.3 0.232 0.785 0.527–1.168 EKR/𝑉/week 4.35 0.64 2.36 5.82 0.033 0.326 0.117–0.912 s dK/𝑉/week 2.93 0.39 1.73 3.88 0.059 0.205 0.040–1.060 /week 2.9 0.3 2.0 3.7 0.413 0.503 0.097–2.606 𝑡dh/week 13.5 2.3 7.7 18.4 0.077 0.786 0.602–1.027 Table 2: Hemodialysis ea men pe iod du a ions and easons o discon inua ion. 𝑁%Du a ion (yea s) Mean SD Min Max Con inuing 19 33.3 2.5 1.7 0.4 5.8 Dea h 16 28.1 2.3 1.6 0.6 6.9 T ansplan a ion 8 14.0 1.4 1.3 0.6 4.6 T ans e o ano he uni 8 14.0 1.3 1.2 0.3 3.8 T ans e o pe i oneal dialysis 3 5.3 2.1 1.4 0.7 3.5 Decision 3 5.3 0.8 0.3 0.6 1.1 The numbe s include hemodialysis ea men pe iods ongoing on Janua y 1, 1998 ( om ha da e on), and inciden pe iods du ing he nine-yea obse a ion ime un il Decembe 31, 2006 (unless e mina ed ea lie ). includes K au oma ically. Renal unc ion is “quali a i ely” be e han dialysis wi h equal u ea clea ance [18]. In heo y, he con inuous-equi alen a e age clea ance basedondoublepoolUKMandincludingRRFis ine,bu he bes measu e is he one mos closely associa ed wi h ou come. Only ew ea lie epo s co ela e mo ali y di ec ly wi h ECC [7, 19–22]. The aim o he p esen p elimina y s udy was o compa e he p ognos ic alue o di e en con inuous- equi alen u ea clea ances as dialysis dose measu es. 2. Subjec s and Me hods The s udy is a e ospec i e egis y analysis om a hospi al p o iding adul hemodialysis se ices in a dis ic wi h a ca chmen a ea o some 50,000 inhabi an s in Eas e n Finland. The obse a ion ime was nine yea s, om Janua y 1, 1998, o Decembe 31, 2006. The ma e ial comp ises 57 con en ional in-cen e hemodialysis ea men pe iods o 51 pa ien s, in o al 114 pa ien yea s. Pe iods las ing unde 90 days a e no included. Pa ien cha ac e is ics a e desc ibed in Table 1. Table 2 p esen s he cha ac e is ics o he dialysis ea men pe iods. “Decision” e e s o a unanimous decision by pa ien and physician o discon inue enal eplacemen he apy. Dosing o dialysis, including ea men equency, was p esc ibed by he i s au ho on mul iple c i e ia (weigh , hyd a ion s a us, p edialysis plasma u ea concen a ion, and o he labo a o y alues, eK𝑡/𝑉 a ge s, and pa ien ’s p e - e ences). Renal diagnosis, como bidi y, unc ional s a us, wai ing o ansplan a ion, age, an icipa ed su i al ime, andp o einca abolic a e(PCR)we eno usedasdosing c i e ia. The pa ien s we e encou aged by a die ician o use a die con aining p o ein 1.2 g/kg/day, bu he ac ual die a y p o ein in ake was no con olled. U ea kine ic modeling wi h in e dialysis u ine collec ion was pe o med mon hly. K was in e pola ed om p e ious and nex measu emen s i u ine collec ion occasionally ailed. RRF was de ec ed in 68% o UKM sessions. In 15% o hem, K was in e pola ed. The numbe s desc ibing he pa ien cha ac e is ics and dialysis dose measu es a e means o each ea men pe iod. Double pool UKM calcula ions we e conduc ed wi h he Solu e-Sol e p og am e sion 1.97 (July 2, 2010, wi h sou ce code) [23], accessed No embe 12, 2015: h p://www.u eak- ine ics.o g/. Dialyze mass a ea coe icien (K0𝐴) epo edby he dialyze manu ac u e is used in Solu e-Sol e in calcula ing dialyze clea ance (Kd) om𝑄band 𝑄dwi h Michaels’ equa ion [24]. Six double pool con inuous-equi alen u ea clea ance measu es we e compa ed: EKR/𝑉 (/week). nEKR (mL/min/1.73 m2). nEKRan (mL/min/1.73 m2). s dK/𝑉 (/week). ns dK (mL/min/1.73 m2). ns dKan (mL/min/1.73 m2). Ad ances in Neph ology 3 Table 3: Dialysis ea men pe iods di ided in o wo g oups wi h app oxima ely equal mean nPCR. EKR/𝑉𝑝 alue Low High Mean SD Mean SD Age Yea s 60.8 13.2 62.5 17.7 0.668 Weigh kg 77.1 21.2 72.9 14.7 0.393 BMI kg/m226.5 6.5 25.7 4.4 0.595 BSA m21.86 0.27 1.81 0.22 0.441 𝑉L 33.7 7.5 29.8 5.1 0.024 nPCR g/kg/day 1.19 0.28 1.12 0.19 0.283 nK mL/min/1.73 m22.0 1.4 1.4 1.4 0.102 nEKR mL/min/1.73 m212.1 1.5 13.0 1.0 0.005 ns dK mL/min/1.73 m28.3 1.1 8.7 0.9 0.240 nEKRan mL/min/1.73 m214.2 2.4 16.2 1.7 0.001 ns dKan mL/min/1.73 m29.8 1.7 10.7 1.3 0.023 EKR/𝑉/week 3.99 0.59 4.72 0.45 <0.001 s dK/𝑉/week 2.75 0.38 3.12 0.30 <0.001 T ea men equency /week 2.8 0.4 3.1 0.2 0.006 T ea men ime h/week 12.6 2.5 14.4 1.7 0.003 T ea men pe iods 𝑛29 28 Women % 31.0 46.4 0.233 Diabe ics % 37.9 46.4 0.516 E n di ng w i h d e a h % 3 7.9 1 7. 9 0 . 0 92 Pa ien yea s 𝑛49.8 64.5 Dea hs 𝑛11 5 Mo ali y /1000 py 221 78 0.049 Thei de ini ions a e desc ibed in he Appendix. EKR is based on ime-a e aged u ea concen a ion; s dK is based on a e - age peak concen a ion. All include di usion, con ec ion, and enal clea ance. 2.1. S a is ical Me hods. Con inuous a iables a e exp essed as means wi h s anda d de ia ions (SD) and minimum and maximum alues. Ca ego ical a iables a e exp essed as pe cen ages. Uni a ia e and mul i a iable bina y logis ic eg ession analyses we e pe o med o iden i y a iables associa ed wi h dea h. Va iables wi h a uni a ia e 𝑝 alue <0.10 we e en e ed in o he mul i a iable models. Odds a ios (ORs) and 95% con idence in e als (CIs) a e epo ed. Linea eg ession analysis was used o e alua e he in e - ac ion o dialysis dose and nPCR (Figu e 1) and he ma e ial was spli in o wo g oups on he basis o EKR/𝑉 and nPCR (Table 3). SPSS 22.0 and STATA 13.1 we e used in s a is ical calcula- ions. The g aph was d awn wi h Excel 2007. 3. Resul s The o e all mo ali y was 140 pe 1,000 pa ien yea s. The main esul s a e shown in Table 1. Mo ali y was signi ican ly associa ed only wi h EKR/𝑉 and nEKR. In mul i a iable analysis, EKR/𝑉 was he only a iable ha ing an associa ion wi h dea h isk (OR = 0.326, CI = 0.117–0.912, and 𝑝 = 0.033). Figu e 1 illus a es he linea eg ession be ween nPCR and EKR/𝑉. To elimina e he con ounding e ec o nPCR on he dose-mo ali y ela ionship, he ma e ial was spli in o wo g oups wi h app oxima ely equal mean nPCR bu di e en mean EKR/𝑉.Thelinesepa a ing heg oupsis depic ed in Figu e 1. Table 3 shows ha he di e ence in mo ali y be ween he low and high dose g oups is s ill signi ican . Men had lowe nPCR, EKR/𝑉,ands dK/𝑉 and highe mo ali y han women (Table 4). Diabe ics had highe weigh , BMI, and BSA bu did no di e signi ican ly om nondiabe - ics in mo ali y (Table 5). Co ela ions be ween some pa ien cha ac e is ics and con inuous-equi alen clea ances a e shown in Table 6. All clea ances co ela e wi h each o he . 4. Discussion The associa ion o six con inuous-equi alen u ea clea ance measu es wi h dea h isk was e alua ed by s a is ical analysis. The mos signi ican p edic o in uni a ia e analysis and he only signi ican one in mul i a iable analysis was EKR/𝑉, calcula ed om TAC (𝑝 = 0.033). The 𝑝 alue o s dK/𝑉 ( om PAC) was 0.059. In he old NCDS, TAC had a close co ela ion wi h ou come han PAC [25]. The s dK concep is complian wi h he peak concen a ion hypo hesis [26], no suppo ed by he p esen esul s. No malizing wi h BSA was es ed by he a iables nEKR and ns dK, wi h mL/min/1.73 m2(o L/week/1.73 m2)as hei uni . nEKR was signi ican ly associa ed wi h dea h isk, bu ns dK was no . In he p esen s udy, Kdwas de i ed om 𝑄b,𝑄d,andK 0𝐴 epo ed by he dialyze manu ac u e . 4Ad ances in Neph ology Table4:Dialysis ea men pe iodsbygende . Women Men 𝑝 alue Mean SD Mean SD Age Yea s 63.3 14.5 60.6 16.1 0.529 Weigh kg 65.2 15.3 81.2 17.4 0.001 BMI kg/m225.7 5.9 26.3 5.3 0.694 BSA m21.66 0.17 1.95 0.22 <0.001 𝑉L 26.1 3.6 35.3 5.7 <0.001 nPCR g/kg/day 1.23 0.23 1.10 0.24 0.043 nK mL/min/1.73 m21.9 1.4 1.6 1.4 0.467 nEKR mL/min/1.73 m212.4 1.1 12.7 1.5 0.401 ns dK mL/min/1.73 m28.2 0.7 8.7 1.1 0.066 nEKRan mL/min/1.73 m214.8 1.9 15.4 2.6 0.349 ns dKan mL/min/1.73 m29.8 1.2 10.5 1.7 0.082 EKR/𝑉/week 4.64 0.57 4.17 0.62 0.005 s dK/𝑉/week 3.07 0.36 2.85 0.39 0.036 T ea men pe iods 𝑛22 35 Ending wi h dea h % 13.6 37.1 0.055 Pa ien yea s 𝑛50.6 63.7 Dea hs 𝑛313 Mo ali y /1000 py 59 204 0.040 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00 0.40 0.80 1.20 1.60 2.00 EKR/V (/week) nPCR (g/kg/day) Di ision line Reg ession line y = 1.50x + 2.66 y = 1.40x + 2.73 R2= 0.29 Figu e 1: Linea eg ession be ween nPCR and dialysis dose (EKR/𝑉) and he line sepa a ing he g oups o Table 3. Calcula ed wi h Michaels’ equa ion [24], a 50% e o in K0𝐴 causes an e o o some 10% in Kdwi h usual 𝑄band 𝑄d. E o s in Kdcause in UKM p opo ional e o s in 𝑉and 𝐺. In EKR/𝑉 and s dK/𝑉, he e o s cancel each o he ou , bu no in nEKR and ns dK. Two o he BSA-no malized con inuous-equi alen clea - ances nEKRan and ns dKan we e calcula ed applying he me hod o Daugi das e al. desc ibed in he Appendix [9, 27]. The an h opome ic o al body wa e is usually la ge compa ed o he kine ic 𝑉. Thus, nEKRan and ns dKan a e highe han he simple BSA-no malized alues. They a e UKM-based con inuous-equi alen hemodialysis dose measu es, whe e he possible e o s in Kda e elimina ed, no malized wi h wo an h opome ic measu es o body size and wi h mL/min/1.73 m2as uni . Howe e , no malizing wi h BSA wi h ei he me hod did no imp o e he p edic i e alue o EKR/𝑉 and s dK/𝑉. In heHEMO ial, heage-adjus edmo ali ydidno di e signi ican ly be ween gende s, bu women did bene i om highe dose [28]. In he p esen s udy, women had lowe mo ali y and go highe EKR/𝑉 and s dK/𝑉 bu sligh ly lowe BSA-no malized doses (Table 4). Como bidi y o he han diabe es was no analyzed. The a he wide ange o dialysis doses in he p esen s udyisp obablydue o heoppo unis icaspec :mo emay be be e , bu wi h la ge pa ien s i is no easy o achie e a high dose (Table 6). In Table 3, he dis ibu ion olume and he p opo ion o men we e highe in he low dose g oup. Men had highe mo ali y and olume and lowe 𝑉-scaled dialysis dose (Table 4). The pa ien cha ac e is ics and dialysis dose measu es ha e mul iple co ela ions o dependencies (Table 6). Figu e 1 shows he linea eg ession be ween nPCR and EKR/𝑉. PCR is a unc ion o EKR/𝑉 o s dK/𝑉 ((B.3) and (B.4) in Appendix). Thus, ma hema ical coupling is ine i able. I is also possible ha nPCR depends on he dialysis dose Ad ances in Neph ology 5 Table5:Dialysis ea men pe iodsbydiabe ics a us. Diabe es 𝑝 alue Yes No Mean SD Mean SD Age Yea s 61.2 14.9 62.0 16.1 0.842 Weigh kg 81.7 18.5 70.2 16.7 0.018 BMI kg/m228.1 6.3 24.6 4.4 0.016 BSA m21.92 0.22 1.78 0.25 0.037 𝑉L 32.9 6.3 30.9 6.9 0.260 nPCR g/kg/day 1.16 0.23 1.14 0.26 0.739 nK mL/min/1.73 m21.5 1.0 1.9 1.6 0.243 nEKR mL/min/1.73 m212.7 0.9 12.4 1.6 0.356 ns dK mL/min/1.73 m28.6 0.8 8.4 1.1 0.350 nEKRan mL/min/1.73 m215.8 1.9 14.6 2.5 0.055 ns dKan mL/min/1.73 m210.7 1.3 9.9 1.7 0.047 EKR/𝑉/week 4.43 0.47 4.29 0.74 0.427 s dK/𝑉/week 2.99 0.27 2.89 0.46 0.360 T ea men pe iods 𝑛24 33 Ending wi h dea h % 25.0 30.3 0.660 Pa ien yea s 𝑛54.3 60.0 Dea hs 𝑛610 Mo ali y /1000 py 110 167 0.439 Table 6: Spea man’s co ela ions, signi ican a he 0.01 le el (2- ailed). Weigh BMI BSA 𝑉nPCR nEKR ns dK nEKRan ns dKan EKR/𝑉s dK/𝑉 Weigh 1 0.854 0.950 0.748 0.352 0.453 0.530 BMI 0.854 1 0.658 0.455 0.393 0.427 BSA 0.950 0.658 1 0.817 0.364 0.430 0.521 𝑉0.748 0.455 0.817 1 0.436 −0.475 −0.354 nPCR 1 0.493 0.519 0.535 0.609 nEKR 1 0.929 0.694 0.711 0.566 0.631 ns dK 0.352 0.364 0.436 0.929 1 0.569 0.686 0.351 0.509 nEKRan 0.453 0.393 0.430 0.493 0.694 0.569 1 0.962 0.821 0.850 ns dKan 0.530 0.427 0.521 0.519 0.711 0.686 0.962 1 0.706 0.809 EKR/𝑉−0.475 0.535 0.566 0.351 0.821 0.706 1 0.961 s dK/𝑉−0.354 0.609 0.631 0.509 0.850 0.809 0.961 1 (causali y)o ha dosingo dialysisisguidedbyu ea concen a ions o adjus ed o p o ein ca abolic a e [29] as ecommended by Go ch e al. [12, 30, 31] ( e e se causali y). All hese ac o s may ha e a ole in he p esen s udy, bu hei sepa a e con ibu ion could no be speci ied. In he HEMO ial, he e ec o dose on nPCR and he ole o ma hema ical couplingwe ees ima ed obesmall[32]. PCR e lec s die a y p o ein in ake, which co ela es wi h nu i ional s a us and ou come [33]. In a ecen la ge egis y ma e ial mo ali y dec eased wi h inc easing nPCR un il 1.3 g/kg/day [34]. Table 3 shows ha in he p esen s udy EKR/𝑉had a signi ican associa ion wi h mo ali y, al hough nPCR was sligh ly highe in he low EKR/𝑉 g oup. nPCR is associa ed wi h mo ali y di ec ly and wi h he dialysis dose h ough he “ ea o high u ea concen a ions” e ec — an example o he mechanisms possibly unde lying he dose- a ge ing bias [35]. nPCR and dialysis dose may ha e a syne gis ic e ec on su i al. A limi a ion o he p esen s udy is he small numbe o pa ien s, which p e en s obus conclusions. On he o he hand, di e en dosing de ini ions we e compa ed in he same ma e ial—a esponse o he challenge p esen ed by Debowska e al. [36]. In summa y, EKR/𝑉and nEKR we e signi ican ly associ- a ed wi h mo ali y bu s dK/𝑉and ns dK we e no . No mal- izing wi h BSA [9, 37] did no imp o e he signi icance o he ECC measu es. Appendix A. Con inuous-Equi alen Clea ance (ECC) EKR (ECCTA )ands dK(ECC PA ) a e based on he de ini ion o clea ance (K): K=𝐸 𝐶.(A.1) 6Ad ances in Neph ology In s eady s a e, he emo al a e (𝐸) equals he gene a ion a e (𝐺), and hus K=𝐺 𝐶.(A.2) In EKR, 𝐶is he ime-a e age concen a ion (TAC) and, in s dK, i is he a e age p edialysis concen a ion (peak a e age concen a ion, PAC): EKR =𝐺 TAC ,(A.3) s dK =𝐺 PAC .(A.4) The uni is, o example, mL/min o L/week. Bo h may be scaled o body size by di iding by u ea dis ibu ion olume 𝑉and exp essed as EKR/𝑉 and s dK/𝑉: EKR/𝑉 = EKR 𝑉,(A.5) s dK/𝑉 = s dK 𝑉.(A.6) 𝐺,𝑉, TAC, and PAC a e de e mined by kine ic modeling, in he p esen s udy wi h Solu e-Sol e . TAC and PAC a e whole-body wa e concen a ions and 𝑉is he pos dialysis o al olume 𝑉𝑡. The mos p ac ical uni o EKR/𝑉 and s dK/𝑉 is /week. nEKR and ns dK a e ECC alues (ECCTA and ECCPA ) no malized wi h body su ace a ea analogically o glome ula il a ion a e o enal clea ance, wi h mL/min/1.73 m2as he uni : nEKR =EKR BSA ∗1.73, ns dK =s dK BSA ∗1.73. (A.7) Daugi das e al. ha e de eloped a me hod o ge a BSA- no malized s dK𝑡/𝑉 [9, 27]: SAn-s dK𝑡/𝑉 = s dK𝑡/𝑉 ∗ Van BSA ∗20,(A.8) whe e Van is an h opome ic TBW in li e s, BSA is in m2, and hecons an 20is hemeano 𝑉/BSA (L/m2)in hei ma e ial. Simila ly, nEKRan and ns dKan can be calcula ed by using a combined an h opome ic scaling ac o Van /BSA (=TBW/BSA): nEKRan =EKR/𝑉 ∗ Van BSA ∗1.73, (A.9) ns dKan =s dK/𝑉 ∗ Van BSA ∗1.73, (A.10) wi h app op ia e uni con e sion ac o s. Van /BSA akes gende in o accoun . In he p esen ma e ial, i s a e age alue was 18.7 (18.3–20.3) L/m2 o women and 21.9 (20.2– 24.5) L/m2 o men. B. nPCR By de ini ion (see (A.4) and (A.6)), 𝐺=s dK/𝑉 ∗PAC ∗𝑉. (B.1) In hemodialysis, nPCR is gene ally calcula ed by he Bo ah equa ion [38] wi h Sa gen ’s modi ica ion [39]: nPCR =(9.35 ∗ 𝐺 + 0.294 ∗ 𝑉) (𝑉/0.58),(B.2) whe e nPCR is exp essed in g/kg/day, 𝐺is exp essed in millig ams o u ea-N/min, and 𝑉is exp essed in L. By sub- s i u ing 𝐺 om (B.1) and using app op ia e uni con e sion ac o s we ge nPCR = 0.0151 ∗ s dK/𝑉 ∗ PAC +0.171, (B.3) whe e nPCR is in g/kg/day, s dK/𝑉is in /week, and PAC is in mmol/L. 𝑉will be elimina ed. nPCR is high i concen a ion (PAC) is high despi e high o no mal clea ance (s dK/𝑉). s dK/𝑉 andPACcanbesubs i u edwi hEKR/𝑉 and TAC: nPCR = 0.0151∗ EKR/𝑉∗ TAC + 0.171. (B.4) nPCR is ine i ably co ela ed wi h s dK/𝑉 and EKR/𝑉.The body su ace a ea-no malized ECC measu es a e no so closely associa ed wi h nPCR. Abb e ia ions BMI: Body mass index = weigh /heigh 2 BSA: Body su ace a ea 𝐶: Concen a ion ECC: Con inuous-equi alen clea ance EKR: Equi alen enal clea ance = 𝐺/TAC EKR/𝑉:EKRscaled o𝑉 eK𝑡/𝑉:Equilib a edK𝑡/𝑉 : Dialysis session equency 𝐺: Gene a ion a e Kd: Dialyze clea ance K :Renalclea ance K0𝐴:Dialyze massa eacoe icien K𝑡: Clea ance ∗session ime K𝑡/𝑉:K𝑡scaled o dis ibu ion olume = Kd∗𝑡 d/𝑉𝑡 nEKR: EKR no malized wi h BSA (mL/min/1.73 m2) nEKRan : EKR no malized wi h BSA and Van (mL/min/1.73 m2) nK :K no malized wi h BSA (mL/min/1.73 m2) ns dK: s dK no malized wi h BSA (mL/min/1.73 m2) ns dKan : s dK no malized wi h BSA and Van (mL/min/1.73 m2) nPCR: PCR scaled o no mal body weigh = PCR/(𝑉/0.58) (g/kg/day) Ad ances in Neph ology 7 PAC: A e age p edialysis concen a ion, peak a e age concen a ion PCR: P o ein ca abolic a e (g/day) py: Pa ien yea s 𝑄b: Dialyze blood low 𝑄d: Dialysa e low RRF: Residual enal unc ion spK𝑡/𝑉:SinglepoolK𝑡/𝑉 s dK: S anda d clea ance = 𝐺/PAC s dK/𝑉:s dKscaled o𝑉 TAC: Time-a e aged concen a ion TBW: To al body wa e (Wa son) = Van 𝑡d: Dialysis session du a ion UF: Ul a il a ion olume (posi i e, i luid is emo ed) UKM: U ea kine ic model 𝑉:Dis ibu ion olume Van : An h opome ic 𝑉=TBW 𝑉𝑡:Pos dialysis𝑉. E hical App o al Thes udywasbasedonananalysiso egis e da acollec ed andu ilizeddu ing he ou ineca eo pa ien sandconduc ed wi h he pe mission o he medical di ec o o he hospi al. The e was no con ol g oup o andomiza ion. The s udy was no p esen ed o an e hics commi ee because he e we e no in e en ions and, acco ding o Finnish law, egis y epo s a e no subjec o e alua ion by e hics commi ees. The pa ien da a we e anonymized and deiden i ied p io o analysis. Compe ing In e es s The au ho s decla e ha hey ha e no compe ing in e es s. Acknowledgmen s The au ho s hank he eam o he Dialysis Uni o Sa onlinna Cen alHospi al o ca e ulbloodandu inesampling. Re e ences [1] E.G.Low ie,Z.Li,N.O s hun,andJ.M.Laza us,“Bodysize, dialysis dose and dea h isk ela ionships among hemodialysis pa ien s,” Kidney In e na ional, ol.62,no.5,pp.1891–1897, 2002. [2] F. K. Po , R. A. Wol e, T. E. Hulbe -Shea on, K. P. 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