Nonadherence in hemodialysis: Associations with mortality, hospitalization, and practice patterns in the DOPPS

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1 Kidney Interntionl, Vol. 64 (2003), pp Nondherence in hemodilysis: Associtions with mortlity, hospitliztion, nd prctice ptterns in the DOPPS RAJIV SARAN, JENNIFER L. BRAGG-GRESHAM, HUGH C. RAYNER, DAVID A. GOODKIN, MARCIA L. KEEN, PAUL C. VAN DIJK, KIYOSHI KUROKAWA, LUIS PIERA, AKIRA SAITO, SHUNICHI FUKUHARA, ERIC W. YOUNG, PHILIP J. HELD, nd FRIEDRICH K. PORT Division of Nephrology, University of Michign, Ann Aror, Michign; University Renl Reserch nd Eduction Assocition, Ann Aror, Michign; Birminghm Hertlnds Hospitl, Birminghm, United Kingdom; Amgen, Inc., Thousnd Oks, Cliforni; Europen Renl Assocition-Europen Dilysis nd Trnsplnt Assocition Registry, Amsterdm, The Netherlnds; Toki University, Kngw, Jpn; Hospitl Generl Vll d Heron, Brcelon, Spin; Kyoto University, Kyoto, Jpn; nd Deprtment of Veterns Affirs Medicl Center, Ann Aror, Michign Nondherence in hemodilysis: Associtions with mortlity, hospitliztion, nd prctice ptterns in the DOPPS. Bckground. Nondherence mong hemodilysis ptients compromises dilysis delivery, which could influence ptient moridity nd mortlity. The Dilysis Outcomes nd Prctice Ptterns Study (DOPPS) provides unique opportunity to review this prolem nd its determinnts on glol level. Methods. Nondherence ws studied using dt from the DOPPS, n interntionl, oservtionl, prospective hemodilysis study. Ptients were considered nondherent if they skipped one or more sessions per month, shortened one or more sessions y more thn 10 minutes per month, hd serum potssium level of 6.0 meq/l, serum phosphte level of 7.5 mg/dl ( 2.4 mmol/l), or interdilytic weight gin (IDWG) 5.7% of ody weight. Predictors of nondherence were identified using logistic regression. Survivl nlysis used the Cox proportionl hzrds model djusting for cse-mix. Results. Skipping tretment ws ssocited with incresed mortlity [reltive risk (RR) 1.30, P 0.01], s were excessive IDWG (RR 1.12, P 0.047) nd high phosphte levels (RR 1.17, P 0.001). Skipping lso ws ssocited with incresed hospitliztion (RR 1.13, P 0.04), s were high phosphte levels (RR 1.07, P 0.05). Lrger fcility size (per 10 ptients) ws ssocited with higher odds rtios (OR) of skipping (OR 1.03, P 0.06), shortening (OR 1.03, P 0.05), nd IDWG (OR 1.02, P 0.07). An incresed percentge of highly trined stff hours ws ssocited with lower OR of skipping (OR 0.84 per 10%, P 0.02); presence of dietitin ws ssocited with lower OR of excessive IDWG (OR 0.75, P 0.08). Conclusion. Nondherence ws ssocited with incresed mortlity risk (skipping tretment, excessive IDWG, nd high phosphte) nd with hospitliztion risk (skipping, high phos- phte). Certin ptient/fcility chrcteristics lso were ssocited with nondherence. Key words: nondherence, noncomplince, DOPPS, outcomes, hemodilysis, skipping tretments. Received for puliction Octoer 30, 2002 nd in revised form Jnury 31, 2003 Accepted for puliction Ferury 28, y the Interntionl Society of Nephrology Hemodilysis is lifesving ut complex therpy. It mkes enormous demnds on ptients with end-stge renl disese (ESRD), therey ffecting their qulity of life [1]. Adherence to complicted tretment regimens ssocited with hemodilysis is vitl. The definition of nondherence nd its ssessment hve oth proven controversil [2, 3]. However, y compromising the delivery of dilysis, nondherence cn ffect oth ptient morid- ity nd mortlity, finding tht is well recognized [4]. It hs een known for some time tht survivl of ESRD ptients is etter in Europe nd Jpn in comprison with the United Sttes fter djustments for ge, gender, nd dietes mellitus [5]. Resons for these dif- ferences re uncler. Differences in prctice ptterns my provide one explntion. A detiled exmintion of prctice ptterns hs een undertken in the Dilysis Outcomes nd Prctice Ptterns Study (DOPPS), n interntionl, oservtionl, prospective hemodilysis study initited etween 1996 nd 1999 [6]. In ddition to prctice ptterns, ptient ehvior nd dherence to prescried tretment my e other determinnts of outcomes. A few studies hve looked t the effect of nond- herence on outcomes, ut these hve een sed minly on ptients from the United Sttes, used limited set of vriles, utilized reltively smll smple sizes, nd hve not lwys mesured the long-term consequences of nondherence. Two studies hve shown tht nondherence to the hemodilysis regimen is ssocited with n incresed risk of deth [7, 8]. One study hs ddressed interntionl comprisons of nondherence in hemodilysis with descriptive pproch [9], sed on questionnires miled to helth professionls cring for hemodilysis ptients in different countries; ssocitions with ptient outcomes were not exmined. The present study ws sed on the hypothesis tht fcilities with lower nondherence rtes re likely to 254

2 Srn et l: DOPPS: Associtions of nondherence in hemodilysis nd outcomes 255 mnifest lower mortlity nd fewer hospitliztions. It informtion ws otined pproximtely every 4 months, ws designed to provide n interntionl perspective on including dtes, dignoses, nd procedures ssocited the mgnitude, distriution, nd predictors of nondher- with ech hospitliztion. ence (oth t ptient nd fcility level). Mesures of nondherence METHODS The ptient mesures of nondherence used in this study re skipping one or more dilysis sessions in 1 Dt source month, shortening one or more dilysis sessions y more The ptient smple ws drwn from the DOPPS dt- thn 10 minutes in 1 month, serum potssium concentrse, which includes informtion out hemodilysis p- tion of 6.0 meq/l, phosphte level of 7.5 mg/dl, or tients in Jpn, the United Sttes, nd five Europen interdilytic weight gin (IDWG) 5.7% of ody weight countries (Frnce, Germny, Itly, Spin, nd the United (the lst cut-off ws sed on 4 kg IDWG in 70 Kingdom, collectively referred to s Euro-DOPPS). A kg ptient). IDWG ws otined using the intrdilytic ntionlly representtive smple of dilysis fcilities ws weight loss, with the ssumption tht ll the weight enrolled in ech country, followed y selection of rndom gined in the interdilytic intervl ws lost during the smple of hemodilysis ptients t ech prticipting dilysis session. These definitions re identicl to those center. The study design nd dt collection instruments used in prior puliction from USRDS specil study were uniform cross ntions. Dt on nondherence [8]. A session missed ecuse of hospitliztion ws not were collected t ech dilysis fcility y center-sed considered nondherence. IDWG ws estimted using reserch coordintor. Detils of study design, fcility the mount of weight removed during hemodilysis smpling, ptient smpling, nd dt collection hve session nd ws expressed s the percentge of ody een pulished previously [10]. weight removed. The prevlence of ech dherence me- A dt vlidtion study ws crried out in ll five sure ws clculted for the initil round of ptients t Europen countries y the contrcting reserch orgnitime of entry into the study. Skipping nd shortening ztion (CRO) in Europe. The CRO extrcted dt from sttus were evluted for the 30 dys prior to enrollment smple of dilysis fcilities, which ws compred with into the DOPPS. IDWG ws clculted from the most the dt extrcted y the stff t those fcilities. While recent hemodilysis tretment efore enrollment, nd forml dt vlidtion hs not een conducted for potssium nd phosphorus mesurements were those othe United Sttes fcilities, the vlues for ge, dietes tined on or efore the enrollment dte. mellitus s primry cuse of ESRD, nd proportion of Prctice pttern nd mortlity models included ll pfemle nd Africn Americn ptients in the United tients enrolled nd used dt t the time of their entry Sttes-DOPPS smple re very similr to the vlues reinto the study. ported for the 1997 United Sttes popultion of in-center hemodilysis ptients y the United Sttes Renl Dt Sttisticl nlysis System (USRDS) [11], suggesting tht the United Sttes- DOPPS dt re indeed representtive of the United The prevlence of ech nondherence mesure ws Sttes ESRD popultion. clculted in ech prticipting continent for the initil The current study reflects dt otined from the cross section of prevlent ptients entering the study. United Sttes (145 fcilities, 3359 ptients), Euro-DOPPS To void the influence of residul renl function on urine (101 fcilities, 2337 ptients), nd Jpn (65 fcilities, output nd, hence, IDWG, ptients who hd een on 1980 ptients). An verge of 30 dult chronic hemodilprevlence clcultions, nd djustments were mde in dilysis for less thn 90 dys were removed from the ysis ptients (ge 17 yers) prticipted from ech fcilll models for ptients who hd een on hemodilysis ity. Study ptients who deprted from fcility were periodiclly replced with ptients who strted hemodicompre the prevlence of ech nondherence mesure for less thn 1 yer. Liner mixed models were used to lysis tretment t the fcility. Dt collection egn in the United Sttes in June 1996, in Europe in My 1998, mong the continents, tking into ccount fcility cluster- nd in Jpn in Ferury For the mortlity nlynd phosphte were djusted for the dy of the week of ing. The nondherence mesures of IDWG, potssium, ses, ptients were followed until Jnury 2002 in the United Sttes, Novemer 2000 in Europe, nd Octoer the lood drw. All ptients were djusted to Wednes in Jpn. Dt were collected using stndrdized dy lood drw vlue to ensure comprility. chrt strction procedure performed y fcilitygistic Predictors of nondherence were identified using lo- sed coordintor t ech dilysis center. Dt included regression. Model specifiction included ge, rce, demogrphic chrcteristics nd comorid conditions. ethnicity, gender, dietic ESRD, depression (presence For this nlysis, dt from n initil cross section of or sence of dignosis of depression in the pst 12 ptients (i.e., prevlent ptients) were used. Follow-up months ws otined from the DOPPS Medicl Ques-

3 256 Srn et l: DOPPS: Associtions of nondherence in hemodilysis nd outcomes tionnire), fcility size, yers on dilysis, smoking, educ- of 7676 ptients used in the predictors of nondherence tion, living sttus, mritl sttus, employment, nd prior nlysis; the full smple ws used for the mortlity nd filed trnsplnttion. These models lso took into c- prctice pttern nlyses. The demogrphic profile of count fcility clustering. The results were expressed s the initil cross section of ptients is given in Tle 1. djusted odds rtios. The proportion of Africn Americns ws higher in the Cox proportionl hzrds models were used to express United Sttes (33.5%) compred with Euro-DOPPS the strength of the reltionship etween ech mesure (1.6%) nd Jpn (0%). While the ge groups were quite of nondherence nd oth mortlity nd hospitliztion. similr cross ntions, ll comorid conditions, except Mortlity models exmined time to deth, while hospitl- smoking nd other crdic conditions, were more prevlent iztion models exmined time to first hospitliztion in the United Sttes. Employment sttus for those fter enrollment into the study. Adjustments were mde 18 to 60 yers old ws highest for Jpn (51.1%) nd for the sme vriles used in the logistic regression lowest for the United Sttes (13.7%); disility rtes nlysis nd were supplemented with 15 summry co- were lowest for Jpn (4.9%) nd higher for the United morid conditions (dietes, coronry hert disese, Sttes (25.5%) nd Euro-DOPPS (20.3%). The propor- congestive hert filure, other crdiovsculr diseses, tion of nursing home residents ws highest for the United hypertension, cererovsculr disese, peripherl vsculr Sttes (8.1%), nd equivlent for Euro-DOPPS (2.3%) disese, lung disese, cncer, HIV/AIDS, gstrointes- nd Jpn (2.6%). The percentge of mrried ptients tinl leed, neurologic disese, psychitric disorder, cellulitis/gngrene, ws highest for Jpn (70.7%) versus 63.5% for Euro- nd dyspne) nd fcility clustering effects. DOPPS nd 47.5% for the United Sttes. Time on ESRD Cox models were strtified y continent. Fcility clustering ws longest for Jpn ( yers). effects were ddressed using roust stndrd esti- mtes sed on the sndwich estimtor [12]. A seprte Distriution of nondherence mesures model ws determined for ech mesure of nondher- Tle 2 shows the prevlence of ech prmeter of ence, s ws model tht included ll five nondherence nondherence studied. In the United Sttes, 7.9% of mesures. For mesuring the ssocition etween hyper- ptients skipped one or more hemodilysis sessions/ phosphtemi nd mortlity, intct prthyroid hormone month compred with only 0.6% in Euro-DOPPS nd (PTH) levels were included in the model, s phosphte 0.6% in Jpn. Similrly, more United Sttes ptients levels could, in prt, reflect underlying hyperprthyroidism. shortened hemodilysis session y 10 minutes or more The medin follow-up time in ech continent in month (19.6%) compred with 9.8% in Euro- ws s follows: Euro-DOPPS 1.8 yers, Jpn 2.0 DOPPS nd 5.7% in Jpn. For ptients with excessive yers, nd the United Sttes 2.9 yers. IDWG, the distriution ws highest in Jpn (34.5%) Logistic regression lso ws employed to investigte compred with 16.8% in the United Sttes nd 11.0% the reltionship etween fcility prctice ptterns nd in Euro-DOPPS. Hyperphosphtemi 7.5g/dL ws ptient nondherence. Prctice ptterns investigted included present mong 15.4% of ptients in the United Sttes, fcility size, percentge of highly trined stff 12.8% in Euro-DOPPS, nd 12.1% in Jpn. Finlly, hours in reltion to direct ptient cre stff hours, percentge hyperklemi of 6.0 meq/l ws seen more commonly of highly trined stff (defined s hving 2 or in Euro-DOPPS (20.0%) thn in Jpn (7.6%) or the more yers of forml nursing trining), presence of United Sttes (6.3%). dietitin in the unit, nd physicin/ptient contct time (minutes/month). These models were djusted for the Ptient level predictors of nondherence list of comorid conditions previously descried, s well Tle 3 shows the results from logistic regression nlyses s for the predictors of nondherence vriles nd continent of possile predictors of the presence of nondhers of residence. Models took into ccount fcility ence mong the hemodilysis popultions studied. Anlyses clustering. All nlyses were crried out using SAS version djusted for ll fctors in this tle, s well s for 8.2 [13]. A P vlue of 0.05 ws considered to those in Tle 1, including Kt/V nd comoridities. Predictors indicte sttisticl significnce. of higher odds of nondherence included younger ge (for skipping, shortening, excessive IDWG, nd hyperphosphtemi), femle gender (for IDWG), Africn RESULTS Americn rce (for skipping nd shortening), employed Ptient demogrphics sttus (hyperphosphtemi), living lone (hyperphosphtemi), There were 14,930 ptients ville for nlysis (8396 smoking sttus (skipping nd IDWG), de- United Sttes, 4075 Euro-DOPPS, nd 2459 Jpnese pression (skipping nd shortening), mritl sttus (hyperphosphtemi), hemodilysis ptients). The ptient numers for the initil nd time on ESRD (shortening, IDWG, cross section smpled were Euro-DOPPS 2337, nd hyperklemi). In ddition, there exists high degree Jpn 1980, nd the United Sttes 3359, for totl of correltion mong different mesurements of

4 Srn et l: DOPPS: Associtions of nondherence in hemodilysis nd outcomes 257 Tle 1. Ptient chrcteristics Chrcteristic Euro-DOPPS Jpn United Sttes Overll Demogrphics Age yers (men, SD) 60.1 (15.2) 58.9 (12.5) 60.8 (15.8) 60.3 (15.2) Mle % Africn Americn % Hispnic % Comoridities % Coronry hert disese Congestive hert filure Other crdic conditions Hypertension Peripherl vsculr disese Crdiovsculr disese Dietes Lung disese Cncer (other thn skin) HIV/AIDS Gstrointestinl leeding Neurologic disese Psychitric disorder Recurrent cellulitis Dyspne Smoking Employment sttus % Employed Disled Eduction % Less thn 12 yers Some college Living sttus % Alone Friends/fmily Nursing home Homeless/prisoner Mrried % Prior kidney trnsplnt % Time on ESRD yers (men, SD) 3.84 (5.4) 6.86 (6.5) 1.9 (3.3) 3.2 (4.9) Averge Kt/V single pool (men, SD) 1.29 (0.31) 1.32 (0.28) 1.31 (0.30) 1.31 (0.30) ESRD is end-stge renl disese. Primry or contriuting Age 60 yers Tle 2. Distriution of nondherence mesures y continent Ptients % Nondherence mesure Euro-DOPPS Jpn United Sttes Overll Skipped 1 hemodilysis session/month Shortened session y 10 minutes IDWG 5.7% of dry weight PO g/dl K 6 meq/l IDWG is interdilytic weight gin. One session skipped (N 136) (46.6%); two sessions skipped (N 67) (23.0%); nd three or more sessions skipped (N 89) (30.4%) One session shortened (N 370) (37.0%); two sessions shortened (N 231) (23.1%); nd three or more sessions shortened (N 399) (39.9%) nondherence (Tle 4). For ny given mesure of nondherence, the odds of ny other mesure of nondherence were greter thn 1.0 nd the mjority of these odds rtios (OR) were sttisticlly significnt. The highest correltion ws seen etween shortening nd skipping hemodilysis sessions (OR 4.91; P 0.05). Correltes of nondherence with mortlity Tle 5 shows the reltive risk (RR) of mortlity for ech of the five mesures of nondherence for ll DOPPS countries. Skipping one or more dilysis sessions month (versus not skipping) ws ssocited with reltive mortlity risk of 1.30 (P 0.01). The reltive mortlity risks

5 258 Srn et l: DOPPS: Associtions of nondherence in hemodilysis nd outcomes Tle 3. Fctors ssocited with nondherence Odds rtios (OR) y nondherence mesure Chrcteristic Skip Shorten IDWG PO 4 K Demogrphics Age (per 10 yers) Mle (vs. femle) Africn Americn (vs. non-africn Americn) Hispnic (vs. non-hispnic) Employment sttus Employed Disled Unemployed nd not disled (reference) Eduction Less thn 12 yers yers (reference) Some college Living sttus Alone Friends/fmily (reference) Nursing home Homeless/prisoner Smoker (yes vs. no) Depressed (yes vs. no) Mrried (yes vs. no) Prior kidney trnsplnt (yes vs. no) Time on ESRD (per yer) ESRD is end-stge renl disese; IDWG is interdilytic weight gin. Adjusted for continent of residence nd ll fctors listed here nd in Tle 4 P 0.05 Tle 4. Associtions of nondherence Odds rtios (OR) y nondherence mesure Chrcteristic Skip Shorten IDWG PO 4 K Skipped 1 hemodilysis session/month Shortened session y 10 minutes IDWG 5.7% of dry weight PO mg/dl K 6 meq/l IDWG is interdilytic weight gin. Adjusted for continent of residence nd ll fctors listed here nd in Tle 3. This tle does not represent correltion mtrix ut insted presents the results from five different logistic regression models. P 0.05 Tle 5. The reltive risk (RR) of mortlity nd first hospitliztion y nondherence mesures RR of mortlity (95% CI) RR of hospitliztion (95% CI) Nondherence mesure Univrite djusted Multivrite djusted Univrite djusted Multivrite djusted Skipped 1 hemodilysis session/month 1.33 ( ) 1.30 ( ) 1.16 ( ) 1.13 ( ) Shortened session y 10 minutes 1.14 ( ) 1.11 ( ) 1.10 ( ) 1.09 ( ) IDWG 5.7% of dry weight 1.14 ( ) 1.12 ( ) 1.00 ( ) 1.00 ( ) PO g/dl 1.19 ( ) 1.17 ( ) 1.07 ( ) 1.07 ( ) K 6 meq/l 1.12 ( ) 1.09 ( ) 0.96 ( ) 0.96 ( ) IDWG is interdilytic weight gin. Adjusted for fctors listed in Tle 1 nd country (used s strt vrile in the Cox model) Adjusted for fctors listed in Tle 1, other nondherence mesures, nd country (used s strt vrile in the Cox model) P 0.14) nd hyperklemi (RR 1.09; P 0.14) were not sttisticlly significnt. The mesures of nondher- ence were independently ssocited with higher mortlity. The presence of comorid conditions showed significnt increse in mortlity, s did lower dilysis dose. for excessive IDWG nd for phosphte levels 7.5 mg/dl were 1.12 (P 0.05) nd 1.17 (P 0.001), respectively. The RR for the ssocition etween mortlity nd hyperphosphtemi incresed to 1.27 (P ) following djustment for intct PTH levels. The RR ssocited with shortening dilysis tretments (RR 1.11;

6 Srn et l: DOPPS: Associtions of nondherence in hemodilysis nd outcomes 259 Tle 6. Prctice ptterns ssocited with nondherence mesures Odds rtio Prctice pttern (individul models) Skip Short IDWG ssocition ws seen etween IDWG nd physicin/ ptient contct time (OR 1.01 per 10 minutes/month, P 0.05). Fcility size Per 10 ptients c 1.02 Fcility 60 ptients (vs. 60 ptients) 1.77 c DISCUSSION Fcility 75 ptients (vs. 75 ptients) c 1.03 Hemodilysis plces multiple nd unvoidle de- Fcility 125 ptients (vs. 125 ptients) c mnds on ptient s lifestyle, relted to the dilysis % Highly trined stff hours (per 10%) 0.84 c % Highly trined stff (per 10%) regimen, dietry nd fluid restrictions, the requirement Dietitin in unit (yes/no) for multiple medictions with potentil side effects, s Physicin contct time (per 10 min/month) c well s mngement of multiple comorid conditions. IDWG is interdilytic weight gin. Nondherence with vrious spects of mngement is Adjusted for vriles in Tle 1, country, nd fcility clustering 0.05 P 0.10 c P 0.05 not uncommon nd is understndle from the ptient s perspective. Quntifiction of the degree of nondherence is clerly required to understnd the impct of tretment on ptient s life. But solutions to this prolem re difficult, nd multiple spects of therpy hve to e Correltes of nondherence with hospitliztion ddressed [4]. However, consensus does not exist s to Tle 5 lso shows the RR for hospitliztion (mod- wht these ought to e. The Ntionl Kidney Foundeled s time to first hospitliztion fter entering the tion/kidney Disese Outcomes Qulity Inititive Clinistudy) for ech of the five mesures of nondherence cl Prctice Guidelines pertining to ptient dherence for ll DOPPS countries. Skipping one or more dilysis rightly emphsize complince with hemodilysis itself sessions month (versus not skipping) ws ssocited ut do not ddress other spects of ptient nondherence with RR of 1.13 (P 0.04) for hospitliztion. For [14]. While no gold stndrd exists, the sensitivity nd phosphte levels 7.5 mg/dl the RR ws 1.07 (P specificity of the cut-off vlues used in this study re not 0.05). The RR results for shortening dilysis tretments known nd my hve influenced the results. (RR 1.09; P 0.09), excessive IDWG (RR 1.00; No prior interntionl comprisons of this mgnitude P 0.91), nd hyperklemi (RR 0.96; P 0.34) nd detil re ville. A rief puliction y Bleyer were not sttisticlly significnt. et l [9] reports cross-sectionl nlysis sed on survey of 86 nurses nd nephrologists from Jpn (N Correltes of nondherence with fcility 21), Sweden (N 16), nd the United Sttes (N 49). prctice ptterns They concluded tht nondherence (sed on missed Dilysis fcility size nd certin fcility prctice pt- dilysis tretments s the min outcome mesure) ws terns were found to e significntly ssocited with non- much more common in the United Sttes compred with dherence mesures (Tle 6). Lrger fcility size (per Sweden nd Jpn nd recommended further study to de- 10 more hemodilysis ptients) ws ssocited with n termine the significnce of their results for ptient survivl. incresed likelihood of skipping (OR 1.03, P 0.06), In this study of representtive smples of hemodilysis shortening (OR 1.03, P 0.05), nd IDWG (OR ptients from seven countries, mesurle indices of 1.02, P 0.07). When looking for n optimum fcility nondherence tht hve een pulished previously [8] size, it ws found tht the risk of skipping significntly were relted to ptient outcomes. Behviorl complince incresed t fcility size of 60 ptients (OR 1.77, mesures of skipping dilysis nd shortening dilysis P 0.001; reference group fcility size 60 ptients). times were studied, s well s indirect mesures of dietry The odds of shortening sessions incresed significntly nd mediction complince such s IDWG, serum phosin fcilities with more thn 75 ptients (OR 1.57, P phte levels, nd serum potssium levels. By djusting 0.006; reference group fcility size 75 ptients), while for ptients who hd een on dilysis for less thn 1 the odds for excessive IDWG went up significntly t yer, n ttempt ws mde in this study to ccount for fcility size of 125 ptients or more (OR 1.45, P the confounding influence of residul renl function on 0.03; reference group fcility size 125 ptients). For IDWG. To ccount for the possiility of survivl is 10% increse in highly trined stff hours, there ws tht could potentilly influence results in n nlysis of decrese in the likelihood of skipping (OR 0.84, P cross section of prevlent ptients, ll nlyses were 0.02). Odds of skipping were 11% lower for every 10% djusted for multiple covrites, including yers on heincrese in highly trined stff in the unit (OR 0.89, modilysis. It lso ws thought desirle to express P 0.06). The presence of dietitin in the fcility ws IDWG s percentge of ody weight, ecuse solute ssocited with lower likelihood of nondherence in vlues cn hve different implictions for individuls of terms of IDWG (OR 0.75, P 0.08), while positive different weight. Furthermore, for the purposes of this

7 260 Srn et l: DOPPS: Associtions of nondherence in hemodilysis nd outcomes study, intrdilytic weight loss served s proxy for [8, 19], lthough this remins controversil suject [20]. IDWG since dt on weights determined for two consec- The mgnitude of mortlity risk ssocited with skipping utive sessions were not uniformly ville. Phosphte dilysis seems lmost s lrge s tht predicted from the levels ove 7.5 mg/dl were more likely to reflect nond- dose effect lone (with Kt/V in the model, the RR for herence with diet nd/or mediction thn levels etween mortlity ws 1.28, P 0.05). This suggests tht the 5.5 mg/dl nd 6.5 mg/dl. These ltter levels could exist detrimentl effect of skipping on mortlity risk is indedespite ptient s ttempt t dherence with diet nd pendent of the delivered dilysis dose nd tht other drugs [15, 16], the result of the reltively inefficient phos- detrimentl fctors or ehviors ssocited with skipping phte clernce chieved y conventionl three times dilysis my contriute to the mortlity risk. Hyperphosweek hemodilysis [17]. phtemi ws significntly ssocited with higher RR Anlysis reveled significnt correltions etween dif- of mortlity, confirming previous reports [21]. It is recogferent mesures of nondherence. Results in this regrd nized tht hyperphosphtemi my not simply reflect re in greement with the study y Leggt et l [8] ut nondherence with regrd to diet. It my lso e secondt vrince with Kimmel et l [18]. In the ltter study, ry to hyperprthyroidism, s well s underdilysis. t three urn hemodilysis centers in the United Sttes When the mortlity nlyses were djusted for intct with predominntly Africn Americn popultions, no PTH levels, the ssocition etween hyperphosphtemi correltion ws oserved etween skipping nd shorten- nd mortlity seemed to strengthen. Hyperklemi ove ing ehvior. The uthors resoned tht this possily 6.0 meq/l filed to chieve sttisticl significnce with reflected different underlying ehviorl cuses for skip- respect to RR of mortlity. The ltter finding, however, ping versus shortening. should not lull prcticing nephrologists into ignoring Multiple demogrphic chrcteristics were oserved mrked hyperklemi s risk fctor for mortlity in n in this study to predict ptient nondherence (Tle 3). individul ptient nd my indicte tht the criterion of Younger ge, Africn Americn rce, femle gender, hyperklemi is not lwys indictive of nondherence disled sttus, living lone, smoking, depression, nd nd my e dependent upon vritions in dietry pttern. time on ESRD were ssocited with higher odds of non- Few studies hve looked t the effect of nondherence dherence with one or more of the mesurements of on mortlity. Held et l [7] reported 14% higher risk nondherence. Some college eduction nd prior kidney of deth from single skipped session in one month. trnsplnt were ssocited with neutrl odds of nond- Ifudu, Henry, nd Friedmn [22], however, reported no herence in ll the domins studied. Living in nursing incresed risk. Leggt et l [8], sed on USRDS spehome ws ssocited with 47% lower odds of skipping cil study, reported definite mortlity ssocitions with tretment, perhps owing to stff supervision nd prenondherence with respect to skipping or shortening sesdictle trnsporttion rrngements to nd from the sions. Bsed on their nlysis, one or more skipped hedilysis unit. A numer of ptient comoridities tested modilysis session per month ws ssocited with 25% were not significntly ssocited with nondherence. higher risk of deth (P 0.01). Shortening three or more Skipping nd shortening hemodilysis tretments is sessions, excessive IDWG, nd hyperphosphtemi lso much more common in the United Sttes thn in Eurocorrelte with heightened mortlity risk, s in this study. DOPPS or Jpn. Excessive IDWG ws more prevlent in Jpn, followed y the United Sttes nd Euroces nd lower mortlity in Jpnese hemodilysis regis- Greter IDWG is ssocited with etter nutritionl indi- DOPPS. High phosphte ws lmost eqully prevlent in ech of the three geogrphic regions, nd potssium try report [23], s well s in single-center study y levels of 6.0 meq/l were more prevlent in Eurocontention tht, fter djustments for ge, rce, gender, Test nd Beud [24]. However, these results support the DOPPS compred with Jpn nd the United Sttes. Furthermore, while skipping one or more dilysis sestions, depression, smoking sttus, eduction, employ- ethnicity, time on ESRD, 15 summry comorid condisions in month ws ssocited with 30% incresed mortlity risk compred with not skipping, shortening ment, nd living sttus, high IDWG is ssocited with dilysis time ws ssocited with n 11% higher RR of higher mortlity risk. It is conceivle tht the J-shped mortlity thn not shortening. Wheres the ltter filed reltionship suggested in the literture [23, 24] is not to rech sttisticl significnce, the effect ws in the exvriles seen ecuse of djustments mde in this study for the pected direction nd likely to e of clinicl relevnce, tht would possily e correlted with low s shortening dilysis time represents ehviorl tennd IDWG (e.g., ge, nursing home residence, depression, dency to other mesures of nondherence in such psecondry comoridity). The high mortlity risk is perhps tients. Skipping dilysis decreses the totl delivered to excessive crdiovsculr urden relted to dose nd my ffect mortlity y tht mechnism. Dose expnded extrcellulr volume. It hs een resoned of dilysis previously hs een shown to hve reltionship quite convincingly tht excessive slt intke increses with RR of mortlity in lrge oservtionl studies thirst, nd ptients should e counseled to restrict slt

8 Srn et l: DOPPS: Associtions of nondherence in hemodilysis nd outcomes 261 intke in the first instnce so s to significntly reduce CONCLUSION their wter intke [25]. This is the first comprehensive interntionl report The dt pertining to hospitliztion s n outcome on nondherence in hemodilysis. Mesures descried of nondherence (Tle 5) indicte tht skipping dilysis include prevlence, ptient nd fcility-level predictors, is significnt risk fctor for hospitliztion (with 16% nd hospitliztion nd mortlity ssocitions. Nondherence, higher risk of hospitliztion in those who skipped one s mesured y skipping nd shortening hemohigher or more sessions of hemodilysis in month versus those dilysis tretments, ws more prevlent in the United who did not skip). The risk of hospitliztion ws 7% Sttes thn in Euro-DOPPS nd Jpn. Jpn demon- higher in those with phosphte level 7.5 mg/dl. These strted the highest prevlence of IDWG per dry weight. results re consistent with the mortlity dt. Previous After djustments for multiple covrites, incresed studies hve not looked t hospitliztion s n outcome mortlity risk ws ssocited with skipping nd shortenwhile evluting nondherence, despite its importnce ing dilysis sessions, high IDWG, nd hyperphosphte- mi. Risk of hospitliztion ws significntly higher for with regrd to ptient moridity nd its effect on cost those ptients who skipped dilysis sessions nd rn high of cre. phosphte levels, with implictions for ptient moridity Fcility size ws correlted y group to see if this ws nd thus cost to helth cre systems. Lrger fcilities consistent liner pttern. As shown in Tle 6, smller were more likely to encounter higher level of nondfcilities (lowest qurtile) were ssocited with the o- herence, especilly with respect to skipping nd shortenservtion on skipping, while the lrger fcilities (highest ing dilysis. Highly trined stff my help to decrese qurtile) were ssocited with IDWG. Thus, fcilities nondherence. The presence of dietitin in the fcility with more thn 60 ptients hd significntly higher OR ws found to lower the odds of excessive IDWG. Approof skipping dilysis (1.77, P 0.001) nd those with prite mesures to minimize the nondherence mong more thn 75 ptients hd significntly higher OR of ptients (oth t the ptient nd fcility levels) re likely shortening dilysis (1.57, P 0.006). It ws only when to reduce mortlity nd hospitliztion risks in hemodilfcility size exceeded 125 ptients tht significntly ysis ptients. Further reserch into effective wys to minhigher OR ws detected for IDWG. This nlysis, the imize nondherence rtes must continue in order to im- uthors elieve, is the first to report reltionship etween prove outcomes mong hemodilysis ptients. fcility size nd mesures of ptient nondher- ence. A prior ntionl study on fcility size nd interme- ACKNOWLEDGMENT dite ptient outcomes did not hve informtion on This study ws funded y n unrestricted grnt from Kirin-Amgen. nondherence in the hemodilysis ptients studied nd Reprint requests to Rjiv Srn, M.D., M.S., Kidney Epidemiology recommended further explortion in this re [26]. nd Cost Center, 315 W. Huron, Suite 240, Ann Aror, MI The results of the current study lso point to the potentil E-mil: rsrn@umich.edu importnce of the percentge of direct ptient-cre stff tht is highly trined. Both the percentge of highly REFERENCES trined stff hours nd of highly trined stff memers 1. Vlderrno F, Jofre R, Lopez-Gomez JM: Qulity of life in end-stge renl disese ptients. Am J Kidney Dis 38: , in fcility seem to hve n effect on ptient nondher ence, s mesured y skipping in given fcility. This 2. Bines LS, Jindl RM: Non-complince in ptients receiving he- result ws sttisticlly significnt (OR 0.84 for 10% modilysis: An in-depth review. 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