Results of improvement in adequacy of intermittent hemodialysis in uremic patients

Transcription

1 314 Grzegorzewsk AE, et l. Roczniki Akdemii Medycznej w Biłymstoku Vol. 50, 2005 Annles Acdemie Medice Bilostocensis Results of improvement in dequcy of intermittent hemodilysis in uremic ptients Grzegorzewsk AE 1,2 *, Bnchowicz W 2, Lender M 1 1 Deprtment of Nephrology, Trnsplntology nd Internl Diseses, Krol Mrcinkowski University of Medicl Sciences, Poznń, Polnd 2 Interntionl Dilysis Center, Rwicz, Polnd Abstrct Key words: Kt/V, blood morphology, ph, PTH, iron. Purpose: Incresing number of ptients, who need intermittent hemodilysis (IHD), is gret chllenge for every society. The im of study is to look if smll increse in IHD dequcy is ble to improve stndrd medicl prmeters. Mteril nd methods: In 40 ptients, Kt/V ws monitored on-line during the middle IHD session in the week, 4 times in ech of 6 consecutive months. In the first month of observtion Kt/V ws lower ( ) thn in the further months, in which Kt/V ws incresing to Blood count ws estimted every month. At the beginning of study period, fter 3 months nd t the end of studies, dry body mss, body mss index (BMI), the blood ph nd serum concentrtion of clcium, phosphte, intct prthormone (ipth), totl protein, lbumin, cholesterol, iron, ferritin, ure nd cretinine were determined. Results: The increse in Kt/V ws ccompnied by rising vlues of hemoglobin (Hb), hemtocrit (Hct), men corpusculr volume, iron, blood ph before nd fter IHD session s well s by decresing vlues of PTH. Sttisticlly unchnged prmeters included dry body mss, BMI, serum concentrtion of totl protein, phosphte, cholesterol nd ferritin s well s white blood cells nd pltelet count. There were correltions between Kt/V nd serum concentrtions of phosphte, PTH, ferritin, Hb nd Hct, indicting tht higher IHD doses were provided to ptients in more dvnced uremic stte. Conclusions: Even smll increse in IHD dequcy leds to beneficil chnges in mngement of uremic ptients. * CORRESPONDING AUTHOR: Deprtment of Nephrology, Trnsplntology nd Internl Diseses ul. Przybyszewskiego Poznń, Polnd Tel: ; Fx: e-mil: licj_grzegorzewsk@yhoo.com (Alicj E. Grzegorzewsk) Received Accepted Introduction Incresing number of uremic ptients, who need dilysis tretment, is gret chllenge for every society but especilly for poor nd developing countries. In Polnd, number of dilyzed ptients incresed from 497 in 1981 to in 2003, tht is over 20-times [1]. Estimted number of ptients on renl replcement therpy is in 2010 [2]. Thus, question how to counterblnce medicl expectncies nd costs is of specil importnce. The im of our study is to look if smll (not very expensive) increse in intermittent hemodilysis (IHD) dequcy, expressed by Kt/V, is ble to improve stndrd medicl prmeters. Mteril nd methods Studies were crried out during six months in 40 uremic ptients (23 women, 17 men) in the ge of yers. All ptients were stble in the month proceeding the study beginning. Cuses of end-stge renl disese included: dibetic nephropthy (12 ptients), chronic glomerulonephritis (7 ptients), chronic tubulointerstitil nephritis without renl stones (4 ptients) or with renl stones (3 ptients), polycystic kidney disese (2 ptients), myloidosis, renl cirrhosis, lupus nephritis, myelom multiplex, chronic lymphtic leukemi (one cse ech). In 7 ptients etiology of end-stge renl disese remined unknown. Arteril hypertension occurred in 25 ptients, crdiovsculr disese in 20 ptients, dibetes mellitus type I in 2 ptients, dibetes mellitus type II in 10 ptients. Ptients were treted with dilyses for 21 (1-185) months. One ptient before strting IHD progrm ws treted with continuous mbultory peritonel dilysis for 14 months. Those, who were dilyzed longer thn one month but shorter thn 6 months (n=6) were lso included into the study, becuse they

2 Results of improvement in dequcy of intermittent hemodilysis in uremic ptients 315 Figure 1. Vlues of on-line Kt/V during the first three month of study on-line Kt/V study durtion (months) first week second week third week fourth week men for the month * p<0.05 s compred to the men for the first month of study hd strted their IHD progrm in plnned mnner with mture rterio-venous fistuls nd did not show ny problems relted to dilysis initition. Ptients (n=36) were tken erythropoietin bet intrvenously in the individul doses rnging from 1000 to 8000 units per week ( units per week including four ptients not receiving erythropoietin). Iron ws supplemented intrvenously in 27 ptients in the doses of 100 mg per week ( mg per week including 13 ptients not receiving iron). Alf-clcidol ws pplied orlly to 12 ptients in the individul doses of 0.25 to 100 g per dy. Clcium crbonte ws dministered in 38 ptients in the doses of 1.0 to 9.0 g per dy. Doses of intrvenous drugs were stble. Prescriptions of orl drugs were lso unchnged, but probbly influenced by ptients complince. In ll ptients, Fresenius dilysis mchines type 4008 S nd polysulfone-bsed membrnes were used. Dilyzers were not reused. Composition of dilysis solution ws not chnged during the study. On-line monitoring of Kt/V ws repetedly performed during the middle IHD session in the ech week in six consecutive months. Mesurements of Kt/V bsed on the conductivity method. Totl body wter, which is ssumed the equl the ure distribution volume, ws clculted using the formul of Wtson et l. [3] for women nd men, respectively. In the first month of study, IHD schedule ws not chnged s compred to tht used in the few previous months in respect of blood nd dilyste flows, durtion of IHD session nd selection of dilyzer. Vlues of on-line Kt/V were stble in weekly evlutions. In the next weeks, efforts were mde to obtin significntly higher Kt/V by n increse in blood flow nd/or dilyste flow. The increse in blood flow ws preferble but not lwys sufficiently possible due to poor blood ccess or ptients intolernce. In such cses, n increse in dilyste flow (from 500 to 800 ) ccompnied trils to enhnce blood flow. In the second month of study, on-line Kt/V in the third nd fourth week ws significntly higher thn men on-line Kt/V for the first month of study, but men vlues for both months were still not different. In the third month of study, vlues of weekly Kt/V estimtions nd men monthly Kt/V were stble nd significntly higher thn men vlue for the first month (Fig. 1). Thus, our im to obtin slightly, but significntly higher Kt/V ws chieved. During the next three months of study the more effective IHD schedule ws mintined, but further efforts to improve dequcy of IHD were not undertken. Hemodilyses were performed three times week. The verge durtion of IHD session ws not significntly different in consecutive months, rnging from hours to hours. The mjority of the ptients (n=34) were dilyzed through rteriovenous fistule (85%). Permnent vsculr ctheters were used in 6 ptients (15%). Effective blood flow incresed from to The dilyste flow incresed from to Results of white blood cell (WBC) count, hemoglobin Hb, hemtocrit Hct, men corpusculr volume MCV nd pltelet (PLT) count were nlyzed every month. At the beginning of study, fter 3 months nd t the end of studies, dry body mss, body mss index (BMI), the blood ph nd serum concentrtion of ionized clcium, phosphte, intct prthormone (ipth), totl protein, lbumin, cholesterol, iron, ferritin, ure nd cretinine were determined. Stndrd lbortory methods were pplied for blood nlysis. BMI ws clculted by the formul of post-dilysis weight in kilogrms per height in squre meters. Results re expressed s men nd one stndrd devition or medin nd rnge of vlues. Distribution of vlues ws

3 316 Grzegorzewsk AE, et l. Figure 2. Vlues of men on-line Kt/V during six months of study men on-line Kt/V checked using Kołmogorow Smirnov test. Sttisticl nlysis included ANOVA test for repeted evlutions nd ANOVA Friedmn test with post hoc Scheffe test. Results of exmined prmeters were correlted to Kt/V vlues, using Spermn or Person correltion coefficients s pproprite. Two vlues of on-line Kt/V were used for correltions: simultneously obtined Kt/V (simultneous Kt/V) nd men Kt/V shown in the month proceeding blood nlysis. A p vlue below 0.05 ws considered s sttisticlly significnt. Results Vlues of Kt/V, obtined during six months of studies, re presented on Fig. 2. Men on-line Kt/V ws incresing from in the first month to in the third month (Tb. 1) nd this higher vlue ws mintined in the next three months of study. As ssumed, there were no further significnt chnges in the men on-line Kt/V fter the second month of study. The increse in Kt/V over six months period ws ccompnied by rising vlues of Hb, Hct, MCV, serum iron concentrtion, blood ph before nd fter IHD session s well s by decresing vlues of serum ipth. Sttisticlly unchnged prmeters included dry body mss, BMI, serum concentrtion of totl protein, lbumin, ionized clcium, phosphte, cholesterol, ure, cretinine nd ferritin s well s WBC nd PLT (Tb. 2). There were correltions between Kt/V nd serum concentrtion of exmined prmeters. For one prmeter only the highest significnt correltion coefficient shown with respective Kt/V during the entire study is presented. Positive correltions were found for phosphte (r=0.324, p=0.041 for simultneous on-line Kt/V; r=0.370, p=0.019 for men on-line Kt/V), ipth (r=0.312, p=0.049 for simultneous Kt/V; r=0.314, p=0.048 for men Kt/V) nd ferritin (r=0.417, p=0.007 for simultneous Kt/V), wheres negtive correltions for Hb (r=-0.369, p=0.019 for simultneous Kt/V; r=-0.376, p=0.017 for men Kt/V) nd Hct (r=-0.365, p=0.021 for simultneous Kt/V; r=-0.374, p=0.017 for men Kt/V) study durtion (months) p< s compred to result obtined in the first month of study b p<0.041 s compred to result obtined in the second month of study,b Tble 1. Chnges in effective blood flow nd dilyste flow during three months of studies Effective Ptient blood flow Simultneous on-line Kt/V showed correltion with the difference between post- nd pre-dilysis serum cretinine level (r=0.354, p=0.025). First month Dilyste flow Men monthly Kt/V Effective blood flow Third month Dilyste flow Men monthly Kt/V men SD medin rnge ,59-1, ,87-1,45 A positive correltion ws shown between durtion of tretment with IHD nd on-line Kt/V (r=0.572, p=0.000 for simultneous Kt/V; r=0.606, p=0.000 for men Kt/V) nd ultr-

4 Results of improvement in dequcy of intermittent hemodilysis in uremic ptients 317 Tble 2. Chnges in exmined prmeters in the course of tretment with intermittent hemodilysis (IHD) with incresing vlues of on-line Kt/V Prmeter filtrtion volume per dilysis session (r=0.370, p=0.018). Durtion of dilysis session ws positively relted to ptients height (r=0.428, p=0.006) nd dry body mss (r=0.547, p=0.0001). Inverse correltions were found for dequcy prmeters nd ptient s chrcteristics: height (r=-0.510, p=0.000 for simultneous Kt/V; r=-0.436, p=0.005 for men Kt/V) nd dry body mss (r=-0.362, p=0.021 for simultneous Kt/V; r=-0.399, p=0.011 for men Kt/V). Discussion The beginning of study The end of study The technique of Kt/V estimtion, bsed on the use of conductivity method, is t present possible in the newer dilysis mchines. It enbles frequent precise Kt/V monitoring, djusted to ptient s needs. In our study we could observe beneficil blood chnges, occurring with the Kt/V increse. p vlue hemoglobin (g/l) hemtocrit (%) men corpusculr volume (fl) iron ( g/dl)* ph before IHD session ph fter IHD session intct prthormone (pg/ml)* 918 ( ) 420 ( ) totl protein (g/l)* NS lbumin (g/l) NS ionized clcium (mmol/l)* NS phosphtes (mmol/l)* NS cholesterol (mmol/l)* NS ure (mmol/l)* NS cretinine ( mol/l)* NS ferritin (ng/dl)* NS white blood cells (K/ml) NS pltelet count (K/ml) NS dry body mss (kg) NS body mss index (kg/m 2 ) NS * serum concentrtion NS non significnt Alredy, in 1983, Hrter [4] hve found tht reducing dilysis dose s reflected by incresing the blood concentrtion of ure nitrogen verged with respect to time (TAC ure ) significntly reduced Hct nd Hb nd incresed the trnsfusion requirements. In 1996 Ifudu et l. [5] showed positive effect of higher URR (72%) on Hct compred to their stndrd URR (61%). Like in our study, ptients were treted with fixed dose of erythropoietin. Ifudu et l. [5] nlyzed two different groups of ptients with similr Hct t the strt of observtion, wheres in our study the dilysis dose ws incresing in the sme ptients. Results from the United Sttes Renl Dt System, published in 1997, confirmed correltion between dilysis dose nd Hct level in IHD ptients treted with erythropoietin [6]. In 2001, it ws shown tht dequte IHD diminished requirement for recombinnt erythropoietin, even in cses in which celulose dilysis membrnes were used [7]. In mentioned study, Hct did not correlte with Kt/V, wheres erythropoietin dose nd Kt/V were inversely correlted [7]. In 2003, Slhudeen et l. [8] presented dt showing Hct in ptients with second genertion spkt/v rnging from <1.23 to >1.68. There were no significnt differences in Hct between groups, however, ptients with highest Kt/V hd significntly lower serum concentrtion of cretinine nd pre-lbumin, wht my indicte undernutrition, lthough serum lbumin level ws lso similr in ll spkt/v groups [8]. In our study, n increse in Kt/V ws not ccompnied with decresed nutritionl prmeters like dry body mss, BMI, or serum concentrtion of totl protein, lbumin, ure, cretinine nd cholesterol. Serum ionized clcium concentrtion ws lso insensitive to chnges in Kt/V. In studies of Hrter [4] plsm clcium, cholesterol nd triglyceride levels did not show significnt chnges with higher TAC ure, but less dequte IHD correlted with incresed risk from crdiovsculr morbidity. When ptients with known cuses of resistence to erythropoietin tretment (iron depletion, luminium overlod, severe hyperprthyroidism, cute or chronic infections) re excluded from the study, the beneficil effect of higher IHD dequcy on Hct my be relted to removl of dilysble low-moleculr-weight inhibitors of erythropoiesis, like spermine nd/or polymine [9,10]. In our study, this effect is lso possible, but dditionlly the influences of serum ipth decrese, serum iron concentrtion increse nd less pronounced metbolic cidosis hve to be considered s contributing fctors. Beneficil effects of more effective IHD on plsm PTH nd correction of metbolic cidosis were lso seen by Hrter [4], when results obtined with high TAC ure (100 mg/dl) were compred to respective vlues shown with TAC ure of 50 mg/dl. Significnt increse in MCV my be relted to higher serum iron level s well s to probbly greter removl of folic cid with higher IHD dequcy, but with fixed vitmin supplementtion. Correltions between Kt/V nd below mentioned prmeters indicte tht higher IHD dequcy ws pplied to uremic ptients in poorer clinicl sttus. These ptients showed higher serum concentrtions of phosphte, ipth, nd ferritin s mrker of inflmmtion, nd lower Hb concentrtion nd Hct. Greter IHD dequcy in underdilyzed ptients could evidently contribute in clinicl improvement. In our study, higher doses of dilysis nd greter ultrfiltrtion volumes per session were provided to ptients treted longer with IHD thn those being on IHD on shorter period of time. Such clinicl intervention my be relted to decrese in residul renl function nd to increse in inflmmtory ctbolic stte over time. In IHD ptients, dry body mss nd BMI were progressively lower with vlues of the second genertion spkt/v incresing from <1.23 to >1.68 [8]. In other study, overweight ptients received less dilysis s mesured by spkt/v, nd conversely, those with lower BMI received higher spkt/v [11]. In our study, Kt/V ws inversely correlted with dry body mss nd height, wht is in greement with cited dt. Such negtive correltion occurred despite longer dilysis sessions provided to ptients

5 318 Grzegorzewsk AE, et l. with greter dry body mss nd height. As expected, Kt/V ws greter in ptients who received longer dilysis sessions. Increses in dilyste flow nd/or in dilysis durtion led to higher costs of IHD session, but optimizing erythropoietin responsiveness nd iron utilistion n dequte dilysis tretment cn contribute to reduction of the costs of mintennce dilytic therpy. In summry, our results indicte tht even smll increse in IHD dequcy my be ccompnied by beneficil chnges in mngement of uremic ptients (better response on erythropoietin, diminished lbortory fetures of secondry hyperprthyroidism, better iron utilistion). Correltion between Kt/V nd exmined prmeters indicte tht higher IHD doses were provided to ptients in more dvnced uremic stte. It my prtilly explin dvntges observed with incrementl IHD dequcy. Acknowledgement The pper ws orlly presented t the 11th Interntionl Symposium on Hemodilysis, Tmp (Florid, USA), References 111. Puk J, Rutkowski B, Lichodziejewsk-Niemierko M, Grend R, Czeklski S, Lo M, Rowiński W, Butembch S. Rport o stnie leczeni nerkozstępczego w Polsce 2003 (Report on the renl replcement therpy in Polnd 2003). Ed. MAKmedi, Gdńsk, Puk J, Rutkowski B, Lichodziejewsk-Niemierko M, Lo M, Rowiński W, Grend R, Czeklski S, Butembch S. Rport o stnie leczeni nerkozstępczego w Polsce 2002 (Report on the renl replcement therpy in Polnd 2002). Ed. Akdemi Medyczn w Gdńsku, Gdńsk, Wtson PE, Wtson ID, Btt RD. Totl body wter volumes for dult mles estimted from simple nthropometric mesurements. Am J Clin Nutr, 1980; 33: Hrter HR. Review of significnt findings from the Ntionl Coopertive Dilysis Study nd recommendtions. Kidney Int, 1983; 23(Suppl. 13): S Ifudu O, Feldmn J, Friedmn EA. The intensity of hemodilysis nd the response to erythropoietin in ptients with end-stge renl disese. N Eng J Med, 1996; 334(7): Young EW, Woods JW, Segied GF, Held PJ, Port FK, Bloembergen WE. Predictors of trget hemtocrit mong erythropoietintreted HD ptients. Am Soc Nephrol, 1997; 8: 259A Movilli E, Cncrini GC, Zni R, Cmerini C, Sndrini M, Miorc R. Adequcy of dilysis reduces the doses of recombinnt erythropoietin independently from the use of biocomptibile membrnes in hemodilysis ptients. Nephrol Dil Trnsplnt, 2001; 16(1): Slhudeen AK, Dykes P, My W. Risk fctors for higher mortlity t the highest levels of spkt/v in hemodilysis ptients. Nephrol Dil Trnsplnt, 2003; 18(7): Rdtke HW, Rege AB, L Mrche MB, Brtos D, Cmpbell RA, Fisher JW. Identifiction of spermine s n inhibitor of erythropoiesis in ptients with chronic renl filure. J Clin Invest, 1981; 67(6): Vnholder R, De Smet R, Hsu C, Vogeleere P, Ringoir S. Uremic toxicity: the middle molecule hypothesis revisited. Semin Nephrol, 1994; 14(3): Slhudeen AK, Fleischmnn EH, Bower JD. Impct of lower delivered Kt/V on the survivl of overweight ptients on hemodilysis. Kidney Int, 1999; 56(6):