Peritoneal Dialysis International, Vol. 26, pp. 458–465 Printed in Canada. All rights reserved. 0896-8608/06 $3.00 + .00 Copyright © 2006 International Society for Peritoneal Dialysis WHAT IS THE LINK BETWEEN POOR ULTRAFILTRATION AND INCREASED MORTALITY IN ANURIC PATIENTS ON AUTOMATED PERITONEAL DIALYSIS? ANALYSIS OF DATA FROM EAPOS Simon J. Davies,1 Edwina A. Brown,2 Werner Reigel,3 Elaine Clutterbuck,4 Olof Heimbürger,5 Nicanor Vega Diaz,6 George J. Mellote,7 Javier Perez–Contreras,8 Renzo Scanziani,9 Christian D’Auzac,10 Dirk Kuypers,11 and Jose C. Divino Filho,12 on behalf of the EAPOS Groupa ♦♦Background: Primary analysis of the European Automated Peritoneal Dialysis Outcomes Study (EAPOS) found that patients with daily ultrafiltration (UF) below a predefined target of 750 mL at baseline experienced increased mortality and continuing low UF over 2 years. ♦♦Setting: Multicenter, prospective observational study of prevalent, functionally anuric patients on automated peritoneal dialysis (APD) treated to predefined standards. ♦♦Methods: Secondary data analysis to determine clinical covariates that might support a link between poor UF and outcome, including pattern of comorbidity, prescription, nutrition as determined by Subjective Global Assessment (SGA), membrane function, and blood pressure (BP). Ultrafiltration was treated as a categorical (comparing patients above and below target at baseline) and continuous dependent variable in univariate and multivariate regression. The relationship between BP and survival was also explored. ♦♦Results: Of 177 patients recruited from 28 centers across Europe, 43 were below the UF target at baseline. Compared to those above target, there were no differences in the spread of comorbidity, type of APD prescription, SGA, BP, hemoglobin, HCO3, or parathyroid hormone, at baseline or at any later time. At baseline, plasma calcium and, at 12 months, plasma phosphate were lower in the low UF group. There was a weak positive correlation between baseline systolic or diastolic BP and UF, which remained on multivariate analysis but accounted for just 9% of the variability in BP. There was no clear relationship between baseline BP and survival, although, if anything, low BP was associated with earlier death. Poor UF was associated with lower mean dialysate glucose concentration during the first 4 months and with consistently worse membrane function. a EAPOS Group: see Appendix. 458 ♦♦Conclusions: The increased mortality associated with poor UF is likely multifactorial and not easily explained by clear differences in comorbidity, nutritional state, or other indices of treatment at baseline. The lower plasma phosphate suggests a subsequent fall in appetite. Poor BP control is unlikely to be the explanation, and a link between lower BP, reduced UF, and earlier death is suggested. Failure to achieve adequate UF due to worse membrane function remains an important and potentially reversible or preventable cause. Perit Dial Int 2006; 26:458–465 www.PDIConnect.com KEY WORDS: Ultrafiltration; solute transport; blood pressure; fluid status; survival; observational cohort study. T he European Automated Peritoneal Dialysis Outcomes Study (EAPOS) was undertaken to establish the efficacy of automated peritoneal dialysis (APD) in functionally anuric patients treated according to previously agreed upon targets for anemia, several biochemical variables, small solute clearance, and daily ultrafiltration (UF) (1–3). The study showed that good clinical outcomes are possible and that the most important predictors of survival are age, comorbidity (especially diabetes), and severe malnutrition. Membrane permeability and small solute clearance, as measured by creatCorrespondence to: S.J. Davies, Department of Nephrology, University Hospital of North Staffordshire, Princes Road, Hartshill, Stoke-on-Trent ST4 7LN, United Kingdom. SimonDavies1@compuserve.com Received 8 September 2005; accepted 22 December 2005. Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 University Hospital of North Staffordshire,1 Stoke on Trent; Charing Cross Hospital,2 London, UK; Klinikum Darmstadt,3 Darmstadt, Germany; Hammersmith Hospital,4 London, UK; Karolinska University Hospital,5 Huddinge, Sweden; Hospital Universitario Dr. Negrin,6 Las Palmas, Spain; Adelaide & Meath Hospital,7 Dublin, Ireland; Hospital General Universitario,8 Alicante, Spain; Ospedale Provinciale Desio,9 Desio, Italy; Hôpital Européen Georges Pompidou,10 Paris, France; U.Z. Gasthuisberg,11 Leuven; Baxter Renal Division Europe,12 Brussels, Belgium PDI JULY 2006 – VOL. 26, NO. 4 EAPOS: ULTRAFILTRATION AND MORTALITY inine clearance, did not predict survival. Strikingly, patients who were below the predefined UF target at the start of the study (>750 mL/day) proved difficult to get above target throughout the 2-year study period, and had a significantly increased mortality. They also had a relatively poor UF capacity at the start of the study compared to those individuals achieving the UF target. There was no difference in solute transport between the two groups. This finding is supported by the recent analysis of survival of anuric peritoneal dialysis (PD) patients by the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) group (4). A number of possible explanations linking poor UF to reduced survival might be put forward. These could include one or more of the following: 14 European countries. Enrollment included 177 of 204 screened patients who were followed for 2 years or until they stopped PD. Clinicians were asked to optimize the dialysis prescription to achieve predefined treatment standards during the first 6 months: these were creatinine clearance ≥60 L/week/1.73 m 2 and daily UF ≥750 mL. Standard pH 5.5, 40-mmol lactate-buffered glucose dialysate was used throughout the study and clinicians used icodextrin at their own discretion to achieve UF targets. In addition, targets were set for blood pressure (BP) and biochemical and hematological parameters as published by the UK Renal Association (5). 1. Increased mortality by association between poor appetite and reduced fluid intake, leading to low UF requirements; 2. Inadequate UF leading to poor control of fluid status due to reluctance to prescribe higher glucose concentrations, or underuse of icodextrin, or inadequate tools for assessing fluid status. This mechanism might increase mortality via hypertension due to increased intravascular volume or expansion of the extracellular interstitial space, a well-documented phenomenon in PD patients. 3. Inability of clinicians to increase UF due to symptomatic hypotension and thus increased mortality by association with worse cardiac function; and 4. An unmeasured difference (e.g., inflammation) in the mix of comorbidity not revealed by the initial analysis. All patients had a peritoneal equilibration test (PET) at baseline and at 12 and 24 months, from which their solute transport status and UF capacity were determined as described previously (6). Weekly creatinine clearance was calculated from creatinine concentration in plasma, urine, and dialysate, 24-hour urine volume, and 24-hour dialysate volume, using PD Adequest (Baxter Healthcare, Brussels, Belgium). Daily UF was calculated as the difference between the volume of total dialysate infused (including both night and daytime fluid) and the volume drained over 24 hours for the same period as the solute collection. Comorbidities were counted for each patient to enable calculation of the Stoke comorbidity score (7,8). Nutrition was assessed at baseline and at yearly visits using Subjective Global Assessment (SGA) (9). Data management was centralized; peritoneal, urine, and dialysate concentrations of creatinine and all other blood tests were measured in local laboratories. The results of these and all other demographic data were collated in the central EAPOS office (Baxter Healthcare), where the PET results and creatinine clearances were calculated. METHODS STUDY DESIGN The design and analysis of primary end points (patient and technique survival) of EAPOS are described in detail elsewhere (1–3). In brief, it was a prospective study of functionally anuric patients (urine volume <100 mL and/or residual renal function <1 mL/minute/ 1.73 m2) treated with APD, undertaken in 28 centers in STATISTICAL DESIGN AND ANALYSIS Previous analysis of the EAPOS data set established a relationship between baseline UF and outcome in two ways. First, there was a categorical analysis according to whether patients were above or below the predefined threshold of daily net UF (750 mL) at the start of the study. Patients below this target, in whom there was an intention to increase UF, had a higher mortality. To reflect this in the present analysis, all available clinical variables were compared according to this baseline categorization, with comparisons between groups being made at different time points using unpaired tests, and 459 Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 The purpose of this secondary analysis of the EAPOS database was to see if any of the above associations could be demonstrated and to see how they interacted with the only factors identified in the primary analysis to be associated with less UF, namely, membrane UF capacity and underutilization of hypertonic glucose in the early stages of the study. PERITONEAL MEMBRANE FUNCTION, SOLUTE CLEARANCES, COMORBIDITY SCORING, NUTRITION, AND DATA MANAGEMENT DAVIES et al. JULY 2006 – VOL. 26, NO. 4 within group longitudinally using paired tests. In the second approach used in the primary analysis, UF was treated as a continuous variable, both at baseline and longitudinally as a time-related variable; in this analysis, increased UF was associated with improved survival independent of age, gender, body surface area (BSA), time on treatment, comorbidity, and nutritional state. To reflect this in the present analysis, UF was treated as a continuous variable when correlated with other clinical factors, using univariate or multivariate regression. To explore the possibility that BP was linked to survival, both a categorical analysis (Kaplan–Meier plot of tertiles combined with between-group comparison using the log rank test) and Cox regression, treating BP as a continuous variable, were used. Data are generally expressed as mean ± SD unless otherwise stated. COMPARISON OF BASELINE CHARACTERISTICS ACCORDING TO BASELINE UF CATEGORY Baseline characteristics are summarized in Table 1. It can be seen that the demographic characteristics were broadly similar in both UF categories. If anything, the prevalence of peripheral vascular disease was greater in the patients with higher daily UF, although the overall spread of comorbidity was very similar. Transplant his- tory, use of icodextrin, and the various approaches to prescribing APD were also the same in both groups. COMPARISON OF LONGITUDINAL VARIABLES ACCORDING TO BASELINE UF CATEGORY Hemoglobin, bicarbonate, parathyroid hormone, BP, and SGA showed no between-group differences at any time point; nor was within-group longitudinal change significant (Table 2). There was a small but significant increase in BSA in the higher UF group (from 1.74 to 1.77 m2), implying that these patients gained weight relatively with the loss of larger patients from PD, resulting in no change in average BSA at each time-point. Plasma calcium was significantly lower at baseline in the low UF category (p = 0.015), but this difference disappeared by 6 months. Patients in this category also tended to have lower phosphate levels, especially at 12 (p < 0.05) and 18 months (NS). At the start of the study, patients below the UF target had dialysis prescriptions with a lower average glucose concentration. Over the next 6 months, this was gradually increased so that it became identical between the two groups for the rest of the study (see Figure 1). Membrane function differed significantly at baseline, such that patients below the UF target had lower UF capacity (p = 0.022) but similar solute transport. Longitudinal membrane function (see Figure 2) showed a significant increase in solute transport and a TABLE 1 Demographic Characteristics of Patients Below and Above Ultrafiltration (UF) Target at Baseline N Cancer Ischemic heart disease Peripheral vascular disease Left ventricular dysfunction Diabetes mellitus Systemic collagen vascular disease Comorbidity: other life-threatening condition Distribution of comorbidity score (0:1:2:3:4:5 comorbidities) Distribution of grade of comorbidity (None:1–2:>2) Gender (male) Age (years) Number of previous transplants (0:1:2:3) Body surface area at baseline (m2) Use icodextrin Distribution of prescription type Dry day Wet day Extra day exchange Tidal 460 Group 1 (UF<750 mL) Group 2 (UF>750 mL) p Value 43 2% 23% 9% 14% 21% 0% 9% 21:13:7:1:1:0 49%:47%:4% 58% 53.7±17.3 28:13:2:0 1.72 47% 131 4% 21% 27% 11% 13% 2% 8% 61:42:18:8:1:1 47%:46%:7% 56.5% 51.4±15.4 91:33:6:1 1.77 46% 0.64 0.71 0.017 0.66 0.20 0.42 0.73 0.83 0.79 0.85 0.72 0.73 0.67 0.99 4.6% 14% 63% 18.4% 6.8% 18.3% 61% 12.2% 0.67 Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 RESULTS PDI PDI JULY 2006 – VOL. 26, NO. 4 EAPOS: ULTRAFILTRATION AND MORTALITY TABLE 2 Longitudinal Changes in Clinical Variables According to Whether Patients Were Below or Above the Ultrafiltration (UF) Target at Baseline Remaining in study (n) BSA (m2) Hemoglobin (g/dL) Phosphate (mmol/L) Calcium (mmol/L) PTH (pg/L) Systolic BP (mmHg) Diastolic BP (mmHg) SGA (score) 0 6 Months into study 12 18 24 <750 mL >750 mL <750 mL >750 mL <750 mL >750 mL <750 mL >750 mL <750 mL >750 mL <750 mL >750 mL <750 mL >750 mL <750 mL >750 mL <750 mL >750 mL <750 mL >750 mL 43 131 1.72 1.77 11.4±1.7 11.0±1.8 1.60±0.48 1.71±0.49 2.35±0.28a 2.46±0.23 27.9±4.1 27.0±3.8 208±76 44±221 133±23 136±25 79±14 82±15 1.63±0.59 1.54±0.57 26 98 1.72 1.77 11.8±1.6 11.5±2.1 1.57±0.51 1.60±0.50 2.36±0.29 2.46±0.23 28.0±4.0 26.5±3.5 118±252 38±299 125±22 131±27 76±16 80±13 — — 18 77 1.74 1.77 11.9±1.5 11.2±1.7 1.38±0.44b 1.62±0.50 2.37±0.29 2.41±0.24 26.5±4.0 26.9±4.2 19±368 51±223 127±29 129±27 76±16 78±16 1.59±0.51 1.55±0.55 11 53 1.78 1.76 11.3±1.7 11.2±1.9 1.24±0.47 1.54±0.50 2.36±0.27 2.38±0.19 26.5±4.0 26.5±3.7 55±279 31±364 123±28 132±29 73±21 78±17 — — 7 48 1.68 1.77c 10.4±1.6 11.2±1.7 1.49±0.48 1.47±0.40 2.30±0.14 2.43±0.22 27.2±6.4 26.8±4.8 85±125 87±310 133±19 130±24 74±11 78±14 1.71±0.76 1.6±0.56 Average % glucose concentration BSA = body surface area; PTH = parathyroid hormone; BP = blood pressure; SGA = Subjective Global Assessment. a p = 0.015, between groups. b p = 0.05, between groups. c p < 0.01, paired test, longitudinal increase from baseline. Figure 1 — Longitudinal average glucose concentration according to whether patients were above (open squares) or below (closed squares) the 750 mL ultrafiltration target at baseline. During the first few months of the study, patients below baseline were prescribed significantly lower glucose concentrations. *p < 0.05. reduction in UF capacity in the patients with UF capacity above target. Membrane function always tended to be worse with respect to UF capacity in those below target, and this was statistically significant on between-group analysis at baseline. Figure 2 — Mean (SE) longitudinal membrane function (at 0, 12, and 24 months) according to whether patients were above (open squares) or below (closed squares) the 750 mL ultrafiltration (UF) target at baseline. *At baseline, the betweengroup difference in UF capacity is significant (p = 0.022). †In those patients >750 mL UF at baseline (open squares), there was a significant longitudinal increase in solute transport and decline in UF by 24 months (p < 0.01). 461 Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 Bicarbonate (mmol/L) UF group DAVIES et al. JULY 2006 – VOL. 26, NO. 4 PDI CROSS-SECTIONAL ANALYSIS OF BASELINE CORRELATES, NUTRITIONAL STATUS, AND DIALYSIS PRESCRIPTION Figure 3 —Patient survival according to baseline systolic blood pressure (BP) divided into tertiles: BP < 126 mmHg (solid light line), 126 – 150 mmHg (solid heavy line), and > 150 mmHg (broken line). There is no significant difference in survival (log rank test, p = 0.23), although the lowest-BP group appears to have a disproportionate early death rate. TABLE 3 Multivariate Regression of Correlates with Systolic Blood Pressure at Baseline ANALYSIS OF BP The relationship between baseline BP and survival was also explored. There was no significant relationship if systolic BP was treated as a continuous variable, with a relative risk of 0.99 per 1 mmHg of increasing pressure (p = 0.188). Blood pressure, which was normally distributed at baseline, was also treated as a categorical variable by tertiles (low <126, medium 126 – 150, and high >150 mmHg) and comparison of survival was made (see Kaplan–Meier plot, Figure 3). There was no significant difference in survival by category (p = 0.23), although it can be seen that survival is not proportional, with a tendency toward earlier death in the lowest BP tertile. Multivariate analysis of clinical covariates associated with baseline systolic BP is summarized in Table 3. In this analysis, the only significant correlation was with net daily fluid removal, and the relationship is positive such that a higher UF was associated with a higher BP. While the overall model is significant (ANOVA p = 0.04), it must be emphasized that it accounts for only 9% of the variability in systolic BP. Adding grade of comorbidity or types of comorbidity had no effect on the overall model. A similar analysis was performed using diastolic BP as the dependent variable (data not shown). This result was almost identical to the systolic BP model, except that, in addition, there was a negative correlation 462 Covariate t Constant 6.09 Age 0.045 Gender (male=1) –1.09 Ultrafiltration at baseline (mL) 2.47 Urine volume at baseline 0.09 SGA at baseline (A=1, B=2, C=3) –1.634 Average glucose concentration of dialysate –0.73 Solute transport a baseline 1.47 p Value <0.001 0.96 0.27 0.015 0.93 0.104 0.47 0.145 Dependent variable: systolic blood pressure. between age and diastolic pressure, with the model accounting for 11% of the variability. DISCUSSION Having shown in the primary analysis of the EAPOS patient cohort that, in those patients who were below the predefined daily UF target of 750 mL, death was more likely, we were anxious to examine the clinical data gathered for any potential explanation of this association. In interpreting these analyses, two important factors must be remembered. First, while EAPOS can be described as an intervention study with predefined minimum targets, Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 Univariate correlations observed at baseline for the whole study population included weak but significant relationships between age and comorbidity score (r = 0.24, p < 0.001) and plasma phosphate (r = –0.34, p < 0.001), but not between any of these covariates and the SGA score. There was correlation between SGA and baseline plasma calcium concentration (r = –0.23, p = 0.003). Average concentration of glucose prescription at baseline correlated weakly with age (r = –0.2, p = 0.012), UF (r = 0.16, p = 0.02), SGA (r = –0.26, p = 0.001), and BSA (r = –0.2, p = 0.011). Analysis of dialysis prescription showed that a dry day (n = 11) was associated with a significantly lower daily UF at baseline: 1006 ± 320 mL compared to 1251 ± 768 mL with all other regimes (p = 0.045). This effect disappeared at 6 months because of prescription change. Survival was not influenced by prescription approach, for example, tidal versus dry/wet day, or wet day with additional exchange. Inequality of size meant that analysis for a center effect was limited to country of origin. No effect of nationality on achieved UF at baseline could be identified (ANOVA p = 0.28). PDI JULY 2006 – VOL. 26, NO. 4 no significant relationship between BP and survival in this population, whether treated as a continuous or a categorical variable on either multivariate or univariate analysis (data not shown), although a tendency for better survival was seen with higher BP. It is conceivable that clinicians were reluctant to press for higher daily UF in patients with relatively low BP in this study, leading to an associated increase in mortality. This cannot have been the main mechanism, however, as betweengroup comparisons of BP were very similar. Another possible explanation for the association between poor outcome and reduced UF in this study would be inflammation (15). One of the main shortcomings of EAPOS is the lack of measurement of either plasma albumin or a marker, such as C-reactive protein. The reasons for this were logistic in that central laboratory storage and measurement of blood samples were beyond the funding arrangements. One possible clue to this link, inflammation, may be inferred from the weak but significant negative correlation between plasma calcium and comorbidity, and the significantly lower plasma calcium observed in the poor UF group at baseline. Clinicians were asked to report corrected calcium levels, but it is possible that this correction was insufficient or omitted in some cases, such that reduced calcium concentration reflected lower albumin levels. If so, this suggests that these patients did have increased inflammation at the start of the study despite similar age and distribution of comorbidity. It seems unlikely, however, that this has a large enough effect alone, as the main clinical correlates with inflammation described in other studies are age, comorbidity, and residual renal function. Following this more detailed analysis, relatively low use of hypertonic glucose and membrane function, specifically UF capacity, remain the clinical variables that are most clearly related to lower achieved UF. In EAPOS, clinicians were allowed to deliver APD according to their clinical preference. This resulted in a number of identifiable patterns of prescription, including dry days, that were associated with slightly less UF at baseline. This effect had disappeared by 6 months and was not used disproportionately in patients below target. It is apparent, however, that care must be taken in using dry days in the prescription given to anuric APD patients with respect to fluid removal, let alone concerns over adequate middle molecule clearance. In conclusion, no clear explanation of the cause of increased mortality associated with reduced UF in this study is apparent from this analysis, although it is likely to be multifactorial. Clinicians need to give special attention to anuric patients who are consistently achieving UF volumes of less that 750 mL per day, especially if 463 Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 there was no randomization, so any attempts to draw cause-and-effect conclusions must be considered with extreme care. Second, because there was a different death rate between the two groups, and thus reason for leaving the study, any conclusions drawn from the longitudinal analyses must consider informative censoring, especially as a reason for lack of difference between groups. With these limitations in mind, we were especially interested to see if differences in BP, nutrition, glucose prescription, membrane function, and approach to dialysis prescription could be implicated in this excess mortality. The SGA is a useful tool in assessing clinical nutritional state, which is well validated in PD patients, in whom SGA is also able to detect longitudinal change and predict survival (10,11). Indeed, it was specifically designed to pick up changes in appetite, gastrointestinal symptoms, and muscle wasting. Baseline SGA, specifically, severe malnutrition (SGA = C), predicted poor survival independently of fluid removal in the EAPOS patients. There is no evidence, however, from this analysis that poor nutrition at baseline was the explanation for reduced survival in those patients whose UF was below target. Furthermore, there was no longitudinal change in BSA, and thus weight, of the low UF patients who remained in the study, in contrast to the significant trend for weight gain in those that were above the UF target and who remained in the study (see Table 2). It can be inferred from the relatively low plasma phosphate, in particular at 12 months, that appetite was reduced in patients with less UF, especially as the mean value at this point of the study is well below any treatment target. The fact that SGA score remained similar between the groups may reflect the fact that patients with worsening SGA had already died or left the study. It could be, therefore, that patients in this group developed worsening nutrition during the study. This might have resulted in a lack of need for greater fluid removal, as perceived by patients or their clinicians, or because poor fluid control itself is associated with worse appetite. It is clear that further studies are required to evaluate the relationship between achieved UF, fluid status, and nutrition. Cross-sectional data would suggest that there is a link, but longitudinal intervention studies are required (12,13). This analysis did not find any evidence to suggest that the excess mortality associated with poor UF was attributable to poor BP control. There was a weak association between increasing BP and UF volume at baseline, but no longitudinal or between-group differences were seen. The relationship between BP and survival in observational studies of dialysis patients can be complex due to reverse causality in patients with low BP (14). There was EAPOS: ULTRAFILTRATION AND MORTALITY DAVIES et al. this is in the context of poor membrane function or declining appetite. While it is not clear why clinicians were reluctant or unable to increase the prescription of glucose and icodextrin in this study, it is certain that, due to differences in membrane function, it would have been necessary in order to gain equivalent fluid removal. It would, therefore, be unsafe to conclude that the association between UF and survival is not amenable to therapeutic intervention. Further studies, preferably involving randomization of treatment strategy, are required in order to understand the relationship between reduced fluid removal, fluid status, and increased mortality, and optimal management. APPENDIX 464 PDI ACKNOWLEDGMENT Baxter Europe (Brussels, Belgium) supported the study by providing data management and statistical support and by supporting investigator meetings. REFERENCES 1. Brown EA, Davies SJ, Heimburger O, Meeus F, Mellotte G, Rosman J, et al. Adequacy targets can be met in anuric patients by automated peritoneal dialysis: baseline data from EAPOS. 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Analysis of the effects of increasing delivered dialysis treatment to malnourished peritoneal dialysis patients. Kidney Int 2000; 57:1743–54. 12. Asghar RB, Green S, Engel B, Davies SJ. Relationship of demographic, dietary, and clinical factors to the hydration status of patients on peritoneal dialysis. Perit Dial Int 2004; 24:231–9. Downloaded from http://www.pdiconnect.com/ by guest on September 30, 2014 Members of EAPOS Group: M. Borras, Hospital Amau de Vilanova, Lerida, Spain; E. Brown, Charing Cross Hospital, London, UK; A. Caillette-Beaudoin, Association Calydial, Irigny, France; E. Clutterbuck, Hammersmith Hospital, London, UK; C. D’Auzac, Hôpital Européen Georges Pompidou, Paris, France; S.J. Davies, University Hospital of North Staffordshire, Stoke-on-Trent, UK; A. Ekstrand, Helsinki University Hospital, Helsinki, Finland; N.E. Frandsen, Central Hospital Esbjerg, Esbjerg, Denmark; P. Freida, Centre Hospitalier Louis Pasteur, Cherbourg, France; C. Friedrichsohn,* Universitätskliniken des Saarlandes, Homburg-Saar, Germany; O. Heimbürger, CAPD-Enheten, Stockholm, Sweden; D. Kuypers, U.Z. Gasthuisberg, Leuven, Belgium; E. MacNamara, Centre Hospitalier Germon et Gauthier, Bethune, France; R. Mactier, Stobhill Hospital NHS Trust, Glasgow, Scotland, UK; G. Malmsten, Orebro Medical Center Hospital, Orebro, Sweden; F. Mastrangelo, Ospedale Multizonale “Vito Fazzi,” Lecce, Italy; F. Meeus, Centre Hospitalier Louise Michel Evry, Evry, France; G.J. Mellotte, Adelaide & Meath Hospital, Dublin, Ireland; J. Perez-Contreras, Hospital General Universitario, Alicante, Spain; W. Riegel,† Universitätskliniken des Saarlandes, Homburg-Saar, Germany; A.S. Rodrigues, Hospital Geral de Santo António, Porto, Portugal; A. Rodriguez-Carmona, Hospital Juan Canalejo, Coruna, Spain; J. Rosman, Westeinde Hospital, Den Haag, The Netherlands; P. Rutherford, Maelor General Hospital, Clydd, Wales, UK; R. Scanziani, Ospedale Provinciale Desio, Desio, Italy; N. Vega Diaz, Hospital Nuestra Senora del Pino, Las Palmas, Spain; A. Vychytil, Univ. Klinik für Innere Medizin III, Wien, Austria; T. Weinreich, Dialyse Institüt Villingen-Schwenningen, Germany. *Present address: Dialyse Institüt Villingen-Schwenningen, Germany; †Present address: Klinikum Darmstadt, Darmstadt, Germany. JULY 2006 – VOL. 26, NO. 4 PDI JULY 2006 – VOL. 26, NO. 4 13. Jones CH, Wells L, Stoves J, Farquhar F, Woodrow G. Can a reduction in extracellular fluid volume result in increased serum albumin in peritoneal dialysis patients? Am J Kidney Dis 2002; 39:872–5. 14. Goldfarb-Rumyantzev AS, Baird BC, Leypoldt JK, Cheung AK. The association between BP and mortality in patients EAPOS: ULTRAFILTRATION AND MORTALITY on chronic peritoneal dialysis. Nephrol Dial Transplant 2005; 20:1693–701. 15. Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. 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