Increasing the Dialysate Sodium Concentration Based on Serum Sodium Concentrations Exacerbates Weight Gain and Thirst in Hemodialysis Patients

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1 Tohoku J. Exp. Med., 2013, 230, Sodium Alignment in Hemodilysis Ptients 117 Incresing the Dilyste Sodium Concentrtion Bsed on Serum Sodium Concentrtions Excerbtes Weight Gin nd Thirst in Hemodilysis Ptients Eun Sook Jung, 1 Jeonghwn Lee, 1 Jy Wook Lee, 1 Hyung-Jin Yoon, 2 Dong Ki Kim, 1 Kook-Hwn Oh, 1 Yon Su Kim, 1 Jin Suk Hn 1 nd Kwon Wook Joo 1 1 Deprtment of Internl Medicine, Seoul Ntionl University College of Medicine, Seoul, Republic of Kore 2 Deprtment of Biomedicl Engineering, Seoul Ntionl University College of Medicine, Seoul, Republic of Kore Most dilysis centers dopt stndrd dilyste sodium prescription. While pre-hemodilysis (HD) serum sodium levels remin reltively constnt in ech individul ptient on chronic HD, these levels cn vry between different ptients. Therefore, single dilyste sodium prescription my not be pproprite for ll ptients. Nineteen stble ptients on mintennce HD were dilyzed for 9 HD sessions with their current dilysis solutions, followed by nother 9 sessions using individulized prescriptions creted by ligning dilyste sodium levels to ech ptient s serum sodium concentrtion. Ptients were divided into 2 groups ccording to whether the verge pre-hd serum sodium concentrtion ws higher thn (higher serum sodium group, n = 13) or equl to (equl sodium group, n = 5) the stndrd dilyste sodium concentrtion. Pre-HD serum sodium levels remined constnt during entire study in both groups. In higher serum sodium group, interdilytic weight gin incresed fter implementtion of the sodium lignment (2.0 ± 0.3 kg vs. 2.3 ± 0.4 kg; P = 0.008). Thirst scores lso incresed in ptients whose dilyste sodium ws incresed by 4 mmol/l (n = 7) (6.4 ± 1.5 vs. 7.6 ± 1.5, P = 0.015). There were no significnt chnges in blood pressure nd intrdilytic complictions. In equl sodium group, significnt differences were not observed in ny prmeters. Our results suggest tht lignment of dilyste sodium levels to ech ptient s serum sodium concentrtion is of little benefit in hemodynmiclly stble ptients who hve pre-hd serum sodium concentrtions higher thn dilyste sodium concentrtion. Keywords: body weight; hemodilysis solutions; hypertension; individulized medicine; sodium. Tohoku J. Exp. Med., 2013 June, 230 (2), Tohoku University Medicl Press Introduction The optiml dilyste sodium concentrtion hs been debted despite numerous investigtions (Flnign 2000). In current clinicl prctice, most hemodilysis (HD) centers dopt stndrd dilyste sodium prescription in the rnge of mmol/l, with only few vritions ccording to ptients clinicl conditions. It hs been documented tht ptients on chronic HD hve reltively constnt pre-hd serum sodium levels, but vry considerbly from ptient to ptient (Peixoto et l. 2010; Bsile et l. 2012). Therefore, single dilyste sodium prescription for ll HD ptients my dversely ffect sodium blnce in significnt proportion of ptients. The direction of sodium flux during HD is determined by the sodium grdient, i.e. the difference in sodium concentrtion between dilyste nd serum. Higher sodium concentrtions in dilyste thn in serum (positive sodium grdient) cn cuse unnecessry intrdilytic sodium gin, resulting in incresed thirst, fluid retention nd hypertension in HD ptients (Munoz Mendoz et l. 2011; Penne nd Sergeyev 2011). In contrst, diffusive sodium loss cn led to intrdilytic symptoms, such s hypotension nd muscle crmps, if the sodium concentrtion is lower in the dilyste thn in serum (negtive sodium grdient). Previous studies hve reported tht reduction in dilyste sodium bsed on pre-hd plsm sodium levels improves thirst, interdilytic weight gin (IDWG), hypertension nd intrdilytic hypotension (Murissco et l. 1985; de Pul et l. 2004; Syrlioglu et l. 2007). However, we could not find ny studies on individulized dilyste sodium prescriptions for ptients who hve serum sodium concentrtions higher thn typicl dilyste sodium concentrtions. The im of the present study ws to determine the shortterm effects of lignment of dilyste nd serum sodium concentrtions on blood pressure (BP), IDWG, thirst nd Received Mrch 6, 2013; revised nd ccepted June 4, Published online June 20, 2013; doi: /tjem Correspondence: Kwon Wook Joo, Deprtment of Internl Medicine, Seoul Ntionl University Hospitl, 28 Yeongeon-dong, Chongno-gu, Seoul, , Republic of Kore. e-mil: junephro@snu.c.kr 117

2 118 E.S. Jung et l. intrdilytic symptoms in ptients with negtive sodium grdients. Mterils nd Methods Subjects The study ws pproved by the Institutionl Review Bord of Seoul Ntionl University Hospitl, nd ech subject gve written informed consent. Nineteen stble ptients on mintennce HD were enrolled in the study. The ptients hd been on dilysis progrm three times week nd hd not hd n ltertion to the composition of their dilyste or dry weights for more thn 3 months before enrollment. All ptients hd Kt/V greter thn 1.2 nd residul dily urine output less thn 300 ml. Dibetic ptients were excluded to void the possible effects of hyperglycemi on serum sodium concentrtions. None of the ptients were receiving hemodifiltrtion or high-flux HD. Study protocol The study ws divided into two 3-week s: the stndrd nd individulized s. During the stndrd, ptients received 9 HD sessions with their current dilysis solutions whose sodium concentrtions were set t 136 (n = 15) or 138 mmol/l (n = 4). During the individulized, ptients received 9 dditionl HD sessions using the individulized prescription in which the dilyste sodium levels were ligned to individul serum sodium levels. The dilyste sodium levels were djusted to even numbers; thus, levels were set t 136 mmol/l if ptient s verge pre-hd serum sodium levels were mmol/l, t 138 mmol/l if mmol/l, nd t 140 mmol/l if mmol/l. One ptient who hd serum sodium concentrtion lower thn the stndrd dilyste sodium concentrtion ws excluded. The remining 18 ptients were divided into 2 groups: those whose verge pre-hd serum sodium concentrtions were higher thn the dilyste sodium concentrtions being used (higher serum sodium group, n = 13) nd those equl to the dilyste sodium concentrtions (equl sodium group, n = 5). The reminder of dilysis prescription, dry weight nd hypertensive medictions were not modified throughout the study. A stndrd low-sodium diet ws enforced, but no dditionl dietry interventions were performed. Mesurements nd definitions Pre-HD serum sodium concentrtions were mesured just before the strt of ech midweek dilysis session using the indirect ion-selective electrode method (Hitchi 7600; Toshib, Tokyo, Jpn). BP vlues were obtined using n utomted BP mesuring device nd IDWG nd ultrfiltrtion volume were recorded t ech session nd the mens for the 9 sessions of ech were used for nlysis. Thirst scores were mesured during the lst 3 sessions of ech using Likert scle questionnire (never = 1; lmost lwys = 5). Hypotensive episodes, nursing interventions nd intrdilytic symptoms were recorded s totl number of events during ech. A hypotensive episode during dilysis ws defined s rpid drop in BP ccompnied by symptoms requiring nursing interventions or s 30 mmhg or greter decrese in systolic BP. The qulity of life ws ssessed t the end of ech using the Kidney Disese Qulity Of Life-Short Form (KDQOL-SF) questionnire. Two ptients who did not complete the questionnire were excluded from the qulity of life nlysis. Bseline comorbidity ws clculted using the Chrlson comorbidity index (Hemmelgrn et l. 2003). Sttisticl nlysis The Mnn-Whitney test nd the Chi-Squre test were used to compre continuous nd ctegoricl vribles, respectively, between groups A nd B. The Wilcoxon signed rnk test nd McNemr s test were used to compre continuous nd ctegoricl vribles, respectively, between the stndrd nd individulized s within ech group. A P vlue of < 0.05 ws considered sttisticlly significnt. All dt were nlyzed using SPSS for Windows (SPSS Inc, Chicgo, IL, USA). Results Bseline demogrphic chrcteristics of the study popultion re shown in Tble 1. Compring with equl sodium group, the ptients in higher serum sodium group were younger nd the verge pre-hd serum sodium concentrtion ws higher. Pre-HD BP levels nd the number of ntihypertensive drugs were lso higher, lthough sttisticlly insignificnt. Six ptients (46.2%) in higher serum sodium group nd 1 ptient (20%) in equl sodium group were on diuretics. All ptients with diuretics tretment hd dily residul urine output less thn 300 ml. There were no significnt differences in sex, HD durtion, IDWG, Kt/V nd Chrlson comorbidity index between the groups. Pre-HD serum sodium levels remined constnt during the entire study in both groups (Tble 2). Ptients in higher serum sodium group hd more IDWG nd ultrfiltrtion volumes during the individulized thn during the stndrd. As result of the sodium lignment, the dilyste sodium concentrtion incresed from 136 to 138 mmol/l in 4 ptients, from 138 to 140 mmol/l in 2 ptients, nd from 136 to 140 mmol/l in 7 ptients, ll in higher serum sodium group. In other words, the dilyste sodium concentrtion incresed by 2 mmol/l in 6 ptients nd by 4 mmol/l in 7 ptients. There were no significnt differences in thirst scores for higher serum sodium group tken s whole. However, when strtified nlyses were performed bsed on the degree of increse in dilyste sodium concentrtion, ptients whose dilyste sodium ws incresed by 4 mmol/l hd higher thirst scores during the individulized thn during the stndrd (7.6 ± 1.5 vs. 6.4 ± 1.5, P = 0.038). There were no significnt differences in BP, KDQOL-SF scores nd intrdilytic complictions between the 2 s in higher serum sodium group (Tble 3, 4). All ptients in equl sodium group were dilyzed without ltering the dilyste prescription throughout the study nd significnt differences were not observed in ny prmeters. Discussion The present study confirmed the results of erlier studies which indicted tht HD ptients hve stble pre-hd serum sodium levels even fter mnipultion of dilyste sodium (de Pul et l. 2004; Bsile et l. 2012). Although some long-term studies hve reveled tht individul osmolr set-points re influenced by chnges in dilyste sodium concentrtion, they vry by less thn 1% (Song et l. 2002;

3 Sodium Alignment in Hemodilysis Ptients 119 Tble 1. Demogrphic chrcteristics of the ptients. P Pre-HD serum sodium (mmol/l) ± ± Age (yers) 52.5 ± ± Mle/Femle 7/6 3/ Durtion of HD (months) 39.9 ± ± Cuse of ESRD n (%) Hypertension 2 (16%) 4 (60%) Chronic glomerulonephritis 7 (54%) 0 (20%) Others 4 (31%) 1 (20%) Number of ntihypertensive drugs 2.7 ± ± Pre-HD SBP (mmhg) ± ± Pre-HD DBP (mmhg) 73.9 ± ± IDWG (kg) 2.0 ± ± Kt/V ure 1.6 ± ± CCI scores 3.3 ± ± Vlues re expressed s men ± s.d., or number (percent). CCI, Chrlson comorbitidy index; HD, hemodilysis; ESRD, end stge renl disese; SBP, systolic blood pressure; DBP, distolic blood pressure; IDWG, interdilytic weight gin. Tble 2. Chnges in serum sodium, dilysis prmeters nd thirst fter sodium lignment. Pre-HD serum sodium (mmol/l) ± ± ± ± 1.4 Pre-HD SBP (mmhg) ± ± ± ± 23.2 Pre-HD DBP (mmhg) 73.9 ± ± ± ± 7.7 Post-HD SBP (mmhg) ± ± ± ± 32.9 Post-HD DBP (mmhg) 79.0 ± ± ± ± 10.3 IDWG (kg) 2.0 ± ± ± ± 0.5 IDWG/dry weight (%) 3.5 ± ± ± ± 0.6 UF (kg) 2.0 ± ± ± ± 0.6 UF/pre-HD weight (%) 3.3 ± ± ± ± 0.9 Thirst score 7.2 ± ± 2.1 b 7.0 ± ± 2.5 Vlues re expressed s men ± s.d. UF, ultrfiltrtion; other bbrevitions s in Tble 1. b Thirst scores in 7 ptients whose dilyste sodium incresed by 4 mmol/l ws significntly higher during the individulized thn during the stndrd (7.6 ± 1.5 vs. 6.4 ± 1.5, P = 0.038). Thein et l. 2007). Therefore, the individulized pproch to prescribing dilyste sodium seems to be resonble wy to void slt loding from high-sodium dilyste nd hemodynmic instbility from low-sodium dilyste. de Pul et l. (2004) hve reported tht individulized prescriptions mde by ligning dilyste sodium to serum sodium decreses thirst, IDWG nd pre-hd BP in ptients with positive sodium grdients. They lso described tht the decrese in dilyste sodium concentrtion contributes to better tolerbility of dilysis becuse less fluid needs to be removed (Sntos nd Peixoto 2008). However, tht study did not include intrdilytic hypotension-prone ptients. A recent smll study showed tht 4 of 6 ptients prone to hypotension requiring n intervention (> 25 % of HD sessions) received more frequent interventions fter individulized reduction of dilyste sodium (Arrmreddy et l. 2012). Moreover recent nlysis of the Dilysis Outcomes nd Prctice Ptterns Study (DOPPS) dtbse hs reported tht ptients with serum sodium levels < 137 mmol/l who were dilyzed with dilyste sodium prescrip-

4 120 E.S. Jung et l. Tble 3. Chnges in KDQOL-SF scores fter sodium lignment. (n = 11 b ) Physicl component summry 48.8 ± ± ± ± 11.1 Mentl component summry 48.9 ± ± ± ± 14.3 Kidney dilysis component summry 57.0 ± ± ± ± 8.0 Vlues re expressed s men ± s.d. b Two ptients who did not complete the KDQOL-SF questionnire were excluded. Tble 4. Chnges in the number of intrdilytic complictions fter sodium lignment. Hypotensive episodes 1 (1%) 0 0 (0%) 1 (2%) Nursing interventions 3 (3%) 2 (2%) 6 (13%) 7 (16%) Trendelenburg s position Modifiction of blood flow Modifiction of UF rte Infusion of sline Intrdilytic symptoms 13 (11%) 4 (3%) 1 (2%) 0 (0%) Hedche Dizziness Crmps Angin Nuse Vlues re expressed s number (percent). UF, ultrfiltrtion. tions > 140 mmol/l hve lower mortlity rte (Hecking et l. 2012). Although low serum sodium concentrtions re ssocited with incresed mortlity nd co-morbid conditions, such s congestive hert filure, higher dilyste sodium prescriptions my hve protective effects by providing intrdilytic crdiovsculr stbility (Wikr et l. 2011). Further studies re needed to determine the longterm efficcy nd sfety of sodium lignment in ptients with positive sodium grdients. In the present study, we found tht incresing the dilyste sodium concentrtion bsed on serum sodium concentrtions excerbted weight gin nd thirst in ptients with negtive sodium grdients. Extrcellulr volume expnsion is predominnt fctor in the pthogenesis of hypertension nd left ventriculr hypertrophy in the HD ptients (Leypoldt et l. 2002). Higher IDWG hs been reported to be ssocited with higher ll-cuse nd crdiovsculr deth risks in chronic HD ptients (Klntr-Zdeh et l. 2009). The existence of the lg phenomenon between extrcellulr volume nd BP chnges my explin our negtive findings in BP fter only 3 weeks of intervention (Twrdowski 2008). Although the number of intrdilytic complictions in higher serum sodium group ws too smll to rech sttisticl significnce, the frequency of ngin episodes ws mrkedly reduced fter sodium lignment s shown in Tble 4. The qulity of life summry scores lso showed trend of improvement, prticulrly for mentl component summry. While these dt suggest tht n increse in the dilyste sodium concentrtion my improve tolerbility of dilysis, we should lso note tht there re mny ptients with negtive sodium grdients without intrdilytic symptoms. Indeed, Munoz Mendoz et l. (2011) showed tht no significnt differences were observed in the frequency of intrdilytic hypotension between ptients with sodium grdients of 0 nd those with positive sodium grdients. Therefore, it ppers tht sodium lignment my not be required for ll ptients with negtive sodium grdients. Incresing the dilyste sodium concentrtion cn be hrmful to ptients with fluid retention nd be helpful in ptients with frequent intrdilytic symptoms.

5 Sodium Alignment in Hemodilysis Ptients 121 The primry limittion of this study is the lck of evlution of sodium blnce during dilysis. We used the indirect potentiometric method to nlyze sodium levels, which requires the correction for plsm wter nd the Donnn fctor. In generl, plsm wter correction virtully cncels the Donnn correction nd zero sodium grdients cn be expected when dilysis fluids re designed to be close to or equl to the plsm concentrtion (Lomonte nd Bsile 2011). In ddition, given tht the ptients in equl sodium group did not exhibit significnt differences in ny prmeters, we believe tht our method for individulizing nd djusting the dilyste sodium levels ws dequte to obtin n isontremic dilysis. Other limittions of this study include its smll smple size, short durtion of the intervention, nd the lck of mesurements of mbultory BP. In conclusion, the individulized prescription of dilyste, creted by ligning dilyste sodium to pre-hd serum sodium, is of little benefit in hemodynmiclly stble HD ptients with negtive sodium grdients. We need to be wre tht even subtle increse in dilyste sodium concentrtion bsed on the serum sodium concentrtion cn led to fluid overlod in ptients without intrdilytic symptoms. The lignment of dilyste nd serum sodium concentrtions should be considered only in the selected subgroups of ptients. Further lrge-scle studies on the selection of these subgroups nd the long-term clinicl significnce of sodium lignment re wrrnted. Acknowledgements The uthors would like to pprecite Prof. Sehyun Kim t Grdute School of Est West Medicl Science, Kyung Hee University for permission to use the Koren version of KDQOL- SF TM 1.3. Conflict of Interest The uthors declre no conflict of interest. References Arrmreddy, R., Sun, S.J., Munoz Mendoz, J., Chertow, G.M. & Schiller, B. (2012) reduction in dilyste sodium in conventionl in-center hemodilysis. Hemodil. Int., 16, Bsile, C., Libutti, P., Lisi, P., Vernqlione, L., Csucci, F., Losurdo, N., Teutonico, A. & Lomonte, C. (2012) Sodium setpoint nd grdient in bicrbonte hemodilysis. J. Nephrol., [Epub hed of print]. de Pul, F.M., Peixoto, A.J., Pinto, L.V., Dorigo, D., Ptricio, P.J. & Sntos, S.F. (2004) Clinicl consequences of n individulized dilyste sodium prescription in hemodilysis ptients. Kidney Int., 66, Flnign, M.J. (2000) Role of sodium in hemodilysis. Kidney Int. Suppl., 76, S72-S78. Hecking, M., Krboys, A., Srn, R., Sen, A., Hörl, W.H., Pisoni, R.L., Robinson, B.M., Sunder-Plssmnn, G. & Port, F.K. (2012) Predilysis serum sodium level, dilyste sodium, nd mortlity in mintennce hemodilysis ptients: the Dilysis Outcomes nd Prctice Ptterns Study (DOPPS). Am. J. Kidney Dis., 59, Hemmelgrn, B.R., Mnns, B.J., Qun, H. & Ghli, W.A. (2003) Adpting the Chrlson Comorbidity Index for use in ptients with ESRD. Am. J. Kidney Dis., 42, Klntr-Zdeh, K., Regidor, D.L., Kovesdy, C.P., Vn Wyck, D., Bunnprdist, S., Horwich, T.B. & Fonrow, G.C. (2009) Fluid retention is ssocited with crdiovsculr mortlity in ptients undergoing long-term hemodilysis. Circultion, 119, Leypoldt, J.K., Cheung, A.K., Delmez, J.A., Gssmn, J.J., Levin, N.W., Lewis, J.A., Lewis, J.L. & Rocco, M.V. (2002) Reltionship between volume sttus nd blood pressure during chronic hemodilysis. Kidney Int., 61, Lomonte, C. & Bsile, C. (2011) Do not forget to individulize dilyste sodium prescription. Nephrol. Dil. Trnsplnt., 26, Munoz Mendoz, J., Sun, S., Chertow, G.M., Morn, J., Doss, S. & Schiller, B. (2011) Dilyste sodium nd sodium grdient in mintennce hemodilysis: neglected sodium restriction pproch? Nephrol. Dil. Trnsplnt., 26, Murissco, A., Frnce, G., Leblond, G., Durnd, C., el Mehdi, M., Crevt, A., Elsen, R., Boobes, Y. & Bz, M. (1985) Sequentil sodium therpy llows correction of sodium-volume blnce nd reduces morbidity. Clin. Nephrol., 24, Peixoto, A.J., Gowd, N., Prikh, C.R. & Sntos, S.F. (2010) Long-term stbility of serum sodium in hemodilysis ptients. Blood Purif., 29, Penne, E.L. & Sergeyev, O. (2011) Sodium grdient: tool to individulize dilyste sodium prescription in chronic hemodilysis ptients? Blood Purif., 31, Sntos, S.F. & Peixoto, A.J. (2008) Revisiting the dilyste sodium prescription s tool for better blood pressure nd interdilytic weight gin mngement in hemodilysis ptients. Clin. J. Am. Soc. Nephrol., 3, Syrlioglu, H., Erkoc, R., Tuncer, M., Soyorl, Y., Esen, R., Gumrukcuoglu, H.A., Dogn, E. & Syrlioglu, M. (2007) Effects of low sodium dilyste in chronic hemodilysis ptients: n echocrdiogrphic study. Ren. Fil., 29, Song, J.H., Lee, S.W., Suh, C.K. & Kim, M.J. (2002) Time-verged concentrtion of dilyste sodium reltes with sodium lod nd interdilytic weight gin during sodium-profiling hemodilysis. Am. J. Kidney Dis., 40, Thein, H., Hloob, I. & Mrshll, M.R. (2007) Associtions of fcility level decrese in dilyste sodium concentrtion with blood pressure nd interdilytic weight gin. Nephrol. Dil. Trnsplnt., 22, Twrdowski, Z.J. (2008) Sodium, hypertension, nd n explntion of the lg phenomenon in hemodilysis ptients. Hemodil. Int., 12, Wikr, S.S., Curhn, G.C. & Brunelli, S.M. (2011) Mortlity ssocited with low serum sodium concentrtion in mintennce hemodilysis. Am. J. Med., 124,