Kidney Interntionl, Vol. 64 (2003), pp. 1120 1124 Anemi in peditric hemodilysis ptients: Results from the 2001 ESRD Clinicl Performnce Mesures Project DIANE L. FRANKENFIELD, ALICA M. NEU, BRADLEY A. WARADY, BARBARA A. FIVUSH, CURTIS A. JOHNSON, nd ANDREW S. BREM Center for Beneficiry Choices, Centers for Medicre & Medicid Services, Bltimore, Mrylnd; Peditric Nephrology, Johns Hopkins University, Bltimore, Mrylnd; Peditric Nephrology, The Children s Mercy Hospitl, Knss City, Missouri; School of Phrmcy, University of Wisconsin, Mdison, Wisconsin; nd Peditric Nephrology, Rhode Islnd Hospitl, Providence, Rhode Islnd Anemi in peditric hemodilysis ptients: Results from the 2001 ESRD Clinicl Performnce Mesures Project. Bckground. Despite improvements in dilysis cre, nemi remins problem in peditric hemodilysis ptients. Methods. To ssess possible explntions for the nemi, clinicl dt were obtined from the Centers for Medicre nd Medicid Services on ll hemodilysis ptients ges 12 to 18 yers between October nd December 2000. Complete dt were vilble for 435 of the 516 ptients (84%). Results. A totl of 160 (37%) ptients hd men hemoglobin of 11 g/dl (nemic). The men ( SD) ge for these ptients ws 15.5 1.8 yers compred to 15.9 1.5 yers for the trget hemoglobin ptients (P 0.05). Men time on chronic dilysis ws similr for both the nemic nd trget hemoglobin ptients ( 100 g/dl) ( 3 yers) but ptients on dilysis 6 months were more likely to be nemic (67%). While nerly ll ptients were treted with erythropoietin, nemic ptients received greter weekly erythropoietin doses (intrvenous, nemi 374 232 units/kg/week vs. trget hemoglobin 246 196 units/kg/week, P 0.001; nd subcutneous, 304 238 units/kg/week vs. 167 99 units/kg/week, P 0.05). A totl of 59% of nemic ptients hd men trnsferrin sturtion (TSAT) 20% compred to 71% of ptients with trget hemoglobin (P 0.01). A men serum ferritin 100 ng/ml ws present in two thirds of the nemic nd trget hemoglobin ptients. Approximtely 60% of ll children were treted with intrvenous iron. The men Kt/V vlues were lower for nemic ptients (1.46 0.4 vs. 1.53 0.3, P 0.05). Anemic ptients were less likely to hve norml serum lbumin (29% nemic vs. 52% trget hemoglobin ptients, P 0.001). Conclusion. In the finl multivrible regression model, dilyzing 6 months, low lbumin, nd men TSAT 20% remined significnt predictors of nemi in children. Key words: peditric hemodilysis, nemi, hemoglobin, lbumin, nutrition. Received for publiction Februry 14, 2003 nd in revised form April 8, 2003 Accepted for publiction My 7, 2003 2003 by the Interntionl Society of Nephrology The Centers for Medicre nd Medicid Services (CMS) lunched the End-Stge Renl Disese (ESRD) Clinicl Performnce Mesures (CPM) Project, formlly the ESRD Core Indictors Project [1], to ssess the cre provided to ptients mintined on chronic dilysis nd to stimulte improvement in tht cre [2]. Prior to 2000, only ptients 18 yers nd older were reported in the published nlyses. Beginning in tht yer, however, peditric hemodilysis ptients, ges 12 to 18 yers, were included in the ESRD CPM Project dt collection [3]. The ESRD CPM Project provided the first comprehensive glimpse into peditric ESRD outcomes bsed on ntionlly vlidted dt set. The genertion of such dt on children with ESRD should ssist in the estblishment of peditric specific guidelines. Evolving guidelines for clinicl cre of peditric ptients my well differ from those lredy estblished for dults. Despite the dvnces in dilysis cre nd the use of erythropoietin, nemi continues to be clinicl problem seen in ptients with ESRD. Approximtely 25% of dult ptient mintined on chronic hemodilysis hve nemi defined by the Ntionl Kidney Foundtion Dilysis Outcome Qulity Inititive (K/DOQI) s hemoglobin vlue less thn 11 g/dl [4]. There ppers to be n increse in morbidity nd mortlity, especilly crdiovsculr morbidity, in dilysis ptients with nemi being significnt risk fctor [5 9]. Upwrd of 75% of children with nemi mintined on chronic hemodilysis exhibit signs of left ventriculr hypertrophy, hrbinger of crdiovsculr morbidity in dulthood [10]. The prevlence of nemi nd its ssocited morbidity in children mintined on chronic dilysis hs yet to be fully determined. In this report, dt on the prevlence of nemi, its mngement, nd its likely contributing fctors were collected on ll children ges 12 to 18 yers of ge who were in-center hemodilysis ptients treted between October nd December 2000. 1120
Frnkenfield et l: Anemi in peditric hemodilysis ptients 1121 METHODS All children ges 12 to 18 yers mintined on chronic in-center hemodilysis identified by the 18 ESRD Networks s live on December 31, 2000 were incorported into the dt set. Stff t individul dilysis units recorded ptient-specific prmeters, including ptient demogrphics, yers on dilysis, ccess type, dilysis clernce, mngement of nemi, nd serum lbumin onto dt collection forms. The clinicl informtion ws collected from October to December 2000. Completed forms on ech ptient were returned to the pproprite network office nd then entered into computerized dtbse (Visul FoxPro, Microsoft Corportion, Redmond, WA, USA). Once entered nd ggregted, the dt were sent to CMS for nlysis. To be prt of the finl nlysis, the ptient form hd to hve the required descriptive informtion nd t lest one hemoglobin, one pired pre- nd postdilysis blood ure nitrogen (BUN), nd one serum lbumin over the October to December study period. Kt/V vlues were clculted using the Dugirds II formul [11]. All fctors considered conceptully importnt nd significntly ssocited with nemi were entered into the multivrible nlysis model. These fctors included gender, rce, (only blck nd white due to smll numbers in other rcil ctegories), Hispnic ethnicity, ge, cuse of ESRD, durtion of dilysis ( 6 months vs. 6 months or longer), men single-pool Kt/V, ccess type, postdilysis body weight, men serum ferritin concentrtion, men trnsferrin sturtion (TSAT) 20% vs. 20%, prescribed dose of erythropoietin, nd men serum lbumin 3.5/ 3.2 g/dl vs. 3.5/3.2 g/dl bromcresol green (BCG)/bromcresol purple (BCP) lbortory methods. Both forwrd nd bckwrd elimintion techniques utilizing the likelihood rtio sttistic were employed. Unless otherwise indicted, dt re expressed s men the stndrd devition with P vlues of less thn 0.05 considered significnt. All sttistic nlyses were conducted using Epi Info, version 6.04 [12] nd SPSS for Windows, version 10.0 [13]. RESULTS A complete dt collection form ws vilble for 435 of the 516 ptients (84%). Of the ptients, 37% (160 of 435) were found to hve men hemoglobin of 11 g/dl (nemi) in the dt collection period. Gender, rce, ethnicity, nd cuse of ESRD did not correlte with the nemi (Tble 1). The men ( SD) ge for the children with nemi ws slightly younger thn tht of the ptients with trget hemoglobin ( 11 g/dl) (15.5 1.8 yers vs. 15.9 1.5 yers, P 0.05). Overll, the number of yers mintined on chronic dilysis ws similr for both the nemic nd trget hemoglobin ptients. However, nemi ws more common mong children who were on dilysis less thn 6 months (48 of 72 ptients) (67%) Tble 1. Ptient chrcteristics Men hemoglobin Men hemoglobin 11 g/dl 11 g/dl Chrcteristic Number (%) Number (%) Totl number of ptients 275 (100) 160 (100) Mle 153 (56) 77 (48) White 127 (46) 72 (45) Blck 114 (41) 71 (44) Hispnic 68 (25) 33 (21) Age (men SD/medin) yers 15.9 1.5/16.2 15.5 1.8/15.8 Cuses of ESRD Congentil/urologic 65 (24) 40 (25) Other cuses combined 114 (41) 70 (44) Durtion of dilysis (men SD/medin) yers 3.1 3.5/1.8 2.9 3.7/1.3 Post dilysis body weight (men SD/medin) kg 55.5 18.6/50.5 56.0 21.7/52.0 P 0.05 compred to children dilyzing 6 months or longer (110 of the remining 359 ptients) (31%) (P 0.001). Nerly ll children were treted with erythropoietin with no differences between the routes of dministrtion (Tble 2). Children with nemi received higher weekly erythropoietin doses (intrvenous, nemi 374 232 units/kg/week vs. trget hemoglobin 246 196 units/kg/ week, P 0.001; nd subcutneous, nemi 304 238 units/kg/week vs. trget hemoglobin 167 99 units/kg/ week, P 0.05). A totl of 59% of nemic children hd men TSAT 20% compred to 71% of the ptients with trget hemoglobin (P 0.01). However, ptients hving men serum ferritin concentrtion 100 ng/ml hd no effect on the presence of nemi. Sixteen percent of nemic children nd 5% of children with trget hemoglobin were reltively iron deficient (defined s men TSAT 20% nd men serum ferritin concentrtion of 100ng/mL; P 0.001). Approximtely 60% of the children were treted with intrvenous iron but the dose given ws not vilble for nlysis. Tretment with orl iron ws not different in the nemic versus children with trget hemoglobin but gin there ws no informtion on dosges prescribed nd ptient complince. The clculted single-pool Kt/V of 1.2 or greter defined dilysis dequcy. The men Kt/V vlues were somewht lower for nemic children (1.46 0.4 vs. 1.53 0.3, P 0.05). Consistent with the lower Kt/V, ctheters were more commonly used s ccess in nemic children (nemi 61% vs. trget hemoglobin 36%, P 0.001). Moreover, men dilysis blood pump flows were lower for ptients with nemi (276 80 ml/min vs. 320 79 ml/min, P 0.001). Medin Kt/V vlues were not different in nemic vs. trget hemoglobin children with fistul or grft (nemi Kt/V 1.52 0.35 vs. trget hemoglobin 1.58 0.31; P 0.279). Within the subset of children dilyzed using ctheters, nemic ptients hd similr clernces (nemi Kt/V 1.42 0.35 vs. trget
1122 Frnkenfield et l: Anemi in peditric hemodilysis ptients Tble 2. Clinicl indictors of cre Men hemoglobin Men hemoglobin 11 g/dl 11 g/dl Chrcteristic Number (%) Number (%) Totl number of ptients 275 (100) 160 (100) Anemi mngement Number of ptients prescribed erythropoietin Intrvenous 250 (92) 138 (90) Subcutneous 21 (8) 18 (12) Weekly erythropoietin dose (men SD/medin) units/kg/week Intrvenous b 246 196/192 374 232/320 Subcutneous c 167 99/138 304 238/216 Men trnsferrin sturtion 20% c 196 (71) 94 (59) Men serum ferritin concentrtion 100 ng/ml 194 (71) 103 (64) Reltive iron deficiency b 14 (5) 25 (16) Number of ptients prescribed intrvenous iron 174 (63) 95 (59) Clernce dt Kt/V (men SD/medin) d 1.53 0.3/1.51 1.46 0.4/1.45 Blood pump flow (men SD/medin) b ml/min 320 79/317 276 80/287 Vsculr ccess Arteriovenous fistul b 106 (39) 28 (18) Arteriovenous grft 71 (26) 35 (22) Ctheter b 98 (36) 97 (61) A few ptients received both intrvenous nd subcutneous erythropoietin; b P 0.001; c P 0.01; d P 0.05 Tble 3. Finl model predicting nemi (hemoglobin 11 g/dl) Odds rtio Predictor (95% confidence intervls) P vlue Durtion of dilysis 6 months 3.5 (1.9, 6.5) 0.001 Men serum lbumin 3.5/3.2 g/dl 3.2 (1.8, 5.8) 0.001 Men trnsferrin sturtion 20% 1.9 (1.2, 3.2) 0.01 Bromcresol green (BCG)/bromcresol purple (BCP) lbortory methods 0.53 g/dl for nemic ptients vs. 3.89 0.46 g/dl for ptients with trget hemoglobin by the BCG method; P 0.001). After controlling for demogrphic nd clinicl prmeters, finl predictors of nemi were being new to dilysis, lower serum lbumin, nd probble iron deficiency s summrized in Tble 3. Fig. 1. Percent of children mintined on chronic hemodilysis with norml lbumin nd nemi. hemoglobin 1.44 0.28) nd pump flows (nemi 263 71 ml/min vs. trget hemoglobin 282 69 ml/min) compred to ptients with trget hemoglobin. Finlly, children with nemi were less likely to hve norml serum lbumin chrcterized s vlue 4.0/3.7 g/dl BCG/BCP methods (Fig. 1). The ssocition between lower serum lbumin nd nemi ws still present in the subset of children dilyzed exclusively with ctheter ccess when clernce nd pump flow were no longer ctive vribles (lbumin 3.56 DISCUSSION Despite the extensive use of erythropoietin nd prescribed iron supplements, over one third of children ges 12 to 18 mintined on chronic hemodilysis hve men hemoglobin of less thn 11 g/dl. In the initil nlysis, lower solute clernces nd lower serum lbumin were fctors tht correlte with nemi in these ptients. Ptients new to dilysis (treted less thn 6 months) were more nemic. The degree of nemi prior to the onset of dilysis my ccount for this finding but this could not be sttisticlly ssessed from the CPM dt set. The yers on hemodilysis, however, did not seem to be significnt fctor. Children with nemi were more likely to be dilyzed
Frnkenfield et l: Anemi in peditric hemodilysis ptients 1123 using ctheter ccess, hd lower pump speeds, nd hd somewht lower Kt/V vlues. Nonetheless, the men dilysis dequcy (Kt/V 1.46 0.4) for the nemic children dilyzed with ctheters exceeded the K/DOQI clernce guidelines for dult hemodilysis ptients [14, 15] (Kt/V 1.2 per tretment). It cme s no surprise then when we observed tht, fter djusting for gender, rce, nd other vribles in the multivrite nlysis, dilysis clernce no longer ppered to be n importnt fctor ccounting for the nemi in these ptients. The questions still to be sked re: is there point beyond which incresing Kt/V brings little further benefit nd could the nemi relly stem from vribles other thn dequcy? It is likely tht ctheter use is directly relted to lower dilysis pump flows nd clernces. At present, there does not pper to be link between ctheter use per se nd nemi independent of clernce s vrible. While fistul ccess hs been considered optimum for hemodilysis mngement [16], there is little outcome dt concerning vsculr ccess in children vilble t the present time. From the 2001 United Sttes Renl Dt System (USRDS) Annul Report dt, over one hlf of the children strting dilysis re trnsplnted within the 2 yers [17]. Moreover, the surgicl cretion of fistul in smller children cn be chllenging techniclly. Given the turnover rte, potentil surgicl difficulties, nd dequcy dt tht pper to exceed K/DOQI guidelines, ctheter plcement my be n pproprite choice for some children t lest initilly. Whether the higher clernces chieved by using fistul ccess would relly ffect nemi nd other ESRD-relted morbidity in children mintined on chronic hemodilysis hs yet to be shown. Almost ll the ptients hd iron supplements prescribed. Dosge of both intrvenous nd orl iron nd the complince of the orl gents were not monitored in this study. Despite the prescription for iron, there ws evidence for persistent iron deficiency (low TSAT nd serum ferritin) in mny children. Insufficient iron dministrtion clerly my hve been fctor contributing to the muted response to the erythropoietin seen in some ptients. Moreover, no informtion concerning the presence of comorbid conditions such s inflmmtory processes nd/or hyperprthyroidism ws vilble. Such dt my lso be importnt in ssessing the degree of nemi since the presence of chronic inflmmtion nd severe hyperprthyroidism could dversely influence the response to erythropoietin. Insufficient dilysis is ssocited with significnt clinicl morbidity, n incresed risk of mortlity [18], nd likely contributes to nemi [18, 19]. However, results from the Ntionl Institutes of Helth (NIH) sponsored Hemodilysis (HEMO) Tril demonstrte tht mrkedly exceeding current dilysis clernce bove current guidelines my not reduce preexisting morbidity or lower mortlity rtes [20]. From the present study, it ppers s though exceeding the guidelines for dilysis dequcy does not ffect the degree of nemi. Alterntive explntions need to be considered to ccount for the nemi. Low serum lbumin nd nemi were relted in dult ptients mintined on hemodilysis but in the context of indequte dilysis clernce [18]. Our observtions rise the possibility tht these two vribles, nemi nd lbumin, re ssocited independent of clernce nd support the view tht poor nutrition my be n dditionl fctor. Reltive iron deficiency in our popultion could lso be mnifesttion of poor nutrition. This hypothesis needs to be studied further using dditionl nd perhps more specific surrogte mrkers for nutrition thn lbumin. ACKNOWLEDGMENTS The views expressed in this mnuscript re those of the uthors nd do not necessrily reflect officil policy of the Centers for Medicre nd Medicid Services. Reprint requests to Andrew S. 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