Type: Original Article

Title: Clinical Impact of a Combined Therapy of Peritoneal Dialysis and Hemodialysis

Running title: Combined Therapy of PD and HD

Subject of manuscript: Peritoneal Dialysis

Authors` full names: Nanae Matsuo,* Keitaro Yokoyama, * Yukio Maruyama, * Yoshimi Ueda,*

Hiraku Yoshida,* Yudo Tanno,* Ryo Yamamoto,* Hiroyuki Terawaki,* Masato Ikeda,* Kazushige

Hanaoka,* Hiroyasu Yamamoto,* Makoto Ogura,* Shuichi Watanabe,† Yasuo Kimura,* Tatsuo

Hosoya*

*Division of Kidney and Hypertension, Department of Internal Medicine, The Jikei University

School of Medicine, Tokyo, Japan; and †Department of Internal Medicine, Kobari General Hospital,

Chiba, Japan

Correspondence: Dr Nanae Matsuo, Division of Kidney and Hypertension, Department of Internal

Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shimbashi Minato-ku, Tokyo 105-

8461, Japan. Phone: +81-3-3433-1111; Fax: +81-3-3433-4297; E-mail: nana77m@jikei.ac.jp

Word Count: 27782981 words

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Abstract

Aims. Although peritoneal dialysis (PD) is recommended as the first-line treatment for end-stage

renal disease, limitations exist to achieving good clinical status when the residual renal function

(RRF) has declined. Combined therapy with PD and hemodialysis (HD) is the treatment of choice

for patients who cannot control body fluid status and/or cannot obtain adequate solute removal by

PD alone. The aim of this study was to evaluate the clinical efficacy effect of this combined therapy

on clinical feature.

Methods. In this retrospective study, fifty-three patients on who received PD and were diagnosed

with underdialysis and/or overhydration with declining RRF were recruited. Parameters of volume

control, uremic solute removal, anemia, and predictors for encapsulating peritoneal sclerosis (EPS)

were compared before and 1 year after combined therapy.

Results. The patients’ hydration status state of the body fluids improved significantly with

reductions in by reducing atrial natriuretic peptide and blood pressure. Serum creatinine and 2

microglobulin also decreased significantly. The hemoglobin level increased remarkably from 8.2 ±

1.6 to 10.7 ± 1.2 g/dl (p<0.01) and the reticulocyte count also increased significantly, even though at

the same time t. The dose of recombinant human erythropoietin administration, however, decreased

significantly. The dialysate to plasma creatinine ratio of creatinine in the dialysate to plasma

obtained from the fast peritoneal equilibration test (PET) decreased significantly from 0.65 ± 0.11 to

0.59 ± 0.13, and the level of interleukin 6 in PET drainage also significantly decreased. Furthermore,

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serum C-reactive protein and fibrinogen decreased significantly.

Conclusions. Combined therapy with PD and HD is an effective way to control fluid status and to

correct inadequate solute removal, leading to which improvement in inflammation, peritoneal

function and s renal anemia.

Keywords: combined therapy-renal anemia-peritoneal equilibration test

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Introduction

Peritoneal dialysis (PD) is recommended as the first-line treatment for end-stage renal disease in

terms of integrated renal replacement therapy (RRT), since PD can preserve residual renal function

(RRF) and fluid homeostasis. Van Biesen et al. reported that PD patient survival is sufficient when

they are transferred to hemodialysis (HD) in a timely manner [1], which is when RRF declines. RRF

contributes significantly to the overall health and well-being of PD patients. It not only provides

small solute clearance but also plays an important role in maintaining fluid balance and removing

middle-molecular uremic toxins, and shows a strong inverse relationship with anemia, inflammation,

and malnutrition in patients on PD. Moreover, many studies have reported that the level of RRF

affects survival of PD patients [2–4], although the reasons are not clearly understood. After the loss

of RRF, limitations exist as to how well PD alone can control both overhydration and inadequate

solute removal. Combined therapy with PD and HD, which comprises 5 days of PD combined with 1

HD session per week, is the treatment of choice for PD patients who cannot control body fluid status

and/or cannot achieve adequate solute removal by PD alone.

We started combined therapy with PD and HD in 1990. This mode of dialysis is thought to

improve uremic symptoms and increase the quality of life in Japan. As of 2008, approximately 1800

patients (20% of all PD patients) have been treated with the combined PD and HD in Japan. Few

reports, however, have described the clinical efficacy of combined therapy [5–7].　

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On the other hand, a combined therapy with PD and HD should be evaluated not only for its

efficacy, but also its influence on the risk of EPS.　Several studies have revealed that prolonged PD

duration is one of the risk factors for EPS, as well as a higher D/P creatinine ratio of the creatinine

concentration in the dialysate to that in the plasma (D/P-cre) obtained from the fast peritoneal

equilibration test (PET), use of a high-glucose PD solution, and a high level of serum 2-

microglobulin (2M) [8–11]. Therefore, we had better checked the predictors of EPS, such as D/P-

cre value, interleukin (IL)-6 level in PD effluent solutions, and the serum 2M level in long-term PD

patients [12–14]. Kawanishi and McIntyre previously reported several benefits of combined therapy

[5-6], however, the influence of prolonged PD duration on the risk of EPS in patients with combined

therapy, has never been evaluated.

The aim of this study was to evaluate the effect of combined therapy on volume control , and

uremic solute removal and anemia, as well as D/P-cre value and IL-6 level, which are predictors of

EPS.

Materials and Methods

There were almost 15% of PD patients who selected combined therapy rather than HD

therapy alone inon our unit. We recruited 53 patients diagnosed with underdialysis and/or

overhydration with declining RRF, who were admitted to hospitals of the Jikei University School of

Medicine to receive PD. Among them, thirty-five patients had received combined therapy as at the

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point of 31st December, 2006 and confirmed the clinical data retrospectively. Eighteen additional

patients of the remainder were recruited who started combined therapy from 1st January, 2007 to 31st

December, 2008 were included in the study. Underdialysis was diagnosed as a creatinine clearance

(Ccr) of <50 L/week, erythropoietin (EPO)-resistant renal anemia [hemoglobin <9 g/dl, even if the

dose of recombinant human (rHu) EPO wasere 6000 U/week, the maximum dose in Japan], and/or

serum 2MG of >30 g/L [11], even if the frequency and volume of PD exchange were increased

maximally according to each patients [including useing of automated peritoneal dialysis (APD),

when patients agreed, and using 2.27% glucose solution in all exchange]. Diagnosis of

overhydration was based on at least one of the following findings continued for 3 months: physical

examination (pretibial pitting edema, uncontrollable high blood pressure, or shortness of breath on

exertion), chest X-ray (signs of congestion or pleural effusion), plasma atrial natriuretic peptide

(ANP) of ≥100 ng/ml [15, 16], even if a 2.27% glucose-based solution and/or a 7.5% icodextrin

solution were used. A 3.86% glucose-based solution is not widely used in Japan because higher

concentrations of glucose have a deleterious effect on the peritoneum. Patients who refused to

continue PD or those who with signs of EPS such as repeated abdominal pain, recurrent continuation

of bloody PD effluent, gradually increasing peritoneal permeability with D/P-cre values >0.82

continued for 12 months or more, and existence presence of peritoneal calcification of peritoneum

on Computed Tomography scan examination, were excluded.

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The profile of the patients’ demographics are is shown in Table 1. Among these 53 patients, 40

were male, and the mean age was 51 years. Mean duration of PD at the start of combined therapy

was 49 months. Theirise underlying original kidney diseases wereinvolved the following: nine with

diabetic nephropathy (9 patients), 35 with chronic glomerulonephritis (35 patients), and six with

nephrosclerosis (six patients). Total weekly CCr, calculated from PD and RRF, at the start of

combined therapy was 50.2 L/week at the start of combined therapy (renal CCr 6.7 L/week). Forty-

four patients satisfied the criteria of were underdialyzedsis, and 22 patients satisfied the criteria of

were overhydratedion (13 patients had both conditionssatisfied both underdialysis and

overhydration). The peritonitis rate before starting combined therapy was one episode every 1 time

per 93 patients month. At our center, the patients who originally started PD therapy were 70%

male; therefore, the percentage of men was greater than women in this study. During the follow-up

period up to 31 December 2008, 21 patients were switched to HD therapy (the reasons were 4 for

inadequate solute removal, 4 for overhydration, 1 for peritonitis and 7 at their for patients request),

two underwent renal transplantation, and two died. None of these patients had developed EPS at that

time. The peritonitis rate after starting combined therapy was one episode every 1 time per 183

patients month.

The Ethics Committee for Biomedical Research of each institutional review board at the Jikei

University School of Medicine approved the study protocol. After obtaining written consent, a native

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arteriovenous fistula was created in the subjects and concomitant HD, once weekly, was initiated

after the fistula shunt had developed sufficiently. No complications related to the fistula shunt were

observed. , including infection or shunt thrombus. High-flux polysulfone membranes were used for

all HD sessions. PD was not carried out basically on the day of thea HD session and the day after

because diffusion isultrafiltration was sufficient with HD for almost all patients, and there were

little differences among the change of indicators of solute removal between among 5 days andand 6

days of PD. However But there were some patients performed who restarted PD on the day after

HD, to gain more ultrafirtration using icodextrin solution. Daily PD dDialysis fluid volume per day

on 5days of PD remained unchanged to maintain the maximum effects of PD. witch we tried just

before starting combined therapy.

RHu-EPO was given as a subcutaneously instead of injection once weekly and was not

administered intravenously before or after a HD session. An oral iron supplement was given orally

according to patient need.

The following clinical parameters, including those obtained in fast PET, were compared before

and 1 year after the concomitant use of HD:.

(1) SThe status of body fluids: home blood pressure (BP) in the morning (the average of a week),

the number of antihypertensive agents prescribed, cardiothoracic ratio of the chest X-ray after the

HD session, plasma ANP level after the HD session, level of RRF, and daily volume of peritoneal

water removal.

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(2) Indicators of solute removal and other laboratory data: blood urea nitrogen (BUN), serum

creatinine, albumin, and 2M.

(3) Indicators of anemia: blood hemoglobin level (Hgb) level before the HD session,and

transferrin saturation (TSAT) before the HD, weekly session, dose of rHu-Epo dose administered per

week, and the reticulocyte count.

(4) Potential indicators of EPS development: , such : the dialysate/plasma creatinine ratio (D/P-

cre) an value andd drainage volume at 4 hours in fast PET, using Cr value of 2.27 ％ glucose

solution (2L), in peritoneum for four hours and serum Cr obtained in the second hour of the test,

level of IL-6 level in PET drainage, serum C-reactive protein (CRP), and blood fibrinogen (Fbg).

The patients who were considered to be clinically difficult to manawhoge during PD/HD

combined therapy, for example, those with continued being underdialyzedsis and overhydratedion

those who needed more concomitant use of HD, those with recurrent peritonitis, and those with the

appearance of signs of EPS, were switched to a single HD therapy.

Statistical analysis

All data are expressed as the mean ± standard deviation, unless otherwise stated. For comparison

of data before and after concomitant use of HD, χ2 test, paired t test, or Wilcoxon signed-ranks test

was used according to the parameters. Stat View 5.0 (SAS Institute, Cary, NC, USA) was used for

the statistical analysis and P < 0.05 was considered as significant.

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Results

Status of body fluids (Table 2)

Body weight changed decreased significantly before and after combined therapy (62.6 ± 11.3

vs. 61.1 ± 12.9 kg, P = 0.01). MoreoverAlso , ANP decreased significantly before and after

combined therapy (123 ± 104 vs. 60 ± 50 pg/ml, P<0.01). The average of systolic BP decreased went

down significantly before and after combined therapy (145 ± 22 vs. 138 ± 17 mmHg, P = 0.03),

although the number of antihypertensive medicationsprescriptions also decreased significantly from

2.6 ± 1.4 to 2.1 ± 1.4 (P < 0.01). The uUrine volume, however, decreased significantly before and

after combined therapy (253 ± 405 vs. 123 ± 331 ml/day, P < 0.01), and weekly urine CCr decreased

significantly from 6.7 ± 10.7 to 1.8 ± 3.9 L/week (P = 0.03). Daily peritoneal ultrafiltration The

volume of daily peritoneal water removal did not change significantly before or after concomitant

HD use.

Indicators of solute removal and other laboratory data (Table 3)

The mean KT/V of single HD session aton 1year was approximately 1.7. Serum creatinine

decreased significantly before and after combined therapy (13.5 ± 3.6 vs. 12.7 ± 3.1 mg/dl, P <

0.01), as well as and 2M decreased significantly (35.9 ± 7.5 vs. 33.1 ± 7.9 g/ml, P < 0.01). In

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contrast, BUN remained unchanged. Serum albumin and phosphate did not change significantly

before or after concomitant HD use.

Indicators of anemia (Table 4)

Blood Hgb levels increased significantly after combined therapy from 8.2 ± 1.6 g/dl before

combined therapy to 10.7 ± 1.2 g/dl at 1 year after (P < 0.01). The dose of rHu-Epo administration

decreased significantly from 5800 ± 1349 U/week before combined therapy to 4556 ± 2058 U/week

after 1 year after of combined therapy (P < 0.01). TSAT and ferritin did not change significantly. (P

= 0.08 and P = 0.50, respectively) before or after the combined therapy. Reticulocyte count increased

significantly from 1.85 ± 1.80 × 104 /l tbefore combined therapy to 3.19 ± 2.16 × 104/l after 1 year

of after combined therapy (P < 0.01).

To exclude hemodilution as a cause of low improvement of the Hgb before combined therapy, ,

we examined the change in Hgb level in six patients whose fluid status did not change after

combined therapy.

In these patients, the Hgb level also increased significantly from 8.9 ± 1.6 to 10.3 ± 0.9 g/dl (P =

0.01).

Fast PET and other indicators of EPS (Table 5)

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D/P-cre decreased significantly from 0.65 ± 0.11 before combined therapy to 0.59 ± 0.13 at 1

year after (P < 0.01). The lLevel of IL-6 in PET drainage decreased significantly from 21.0 (range:

2.1-66.4) pg/ml before combined therapy to to 10.3 (range: 0.8-23.5) pg/ml 1 year after (P = 0.03).

The PET drainage volume did not change significantly. Serum CRP decreased significantly

decreased from 0.5 mg/dl (range: 0.01–7.4) to 0.2 mg/dl (range: 0.01–0.6), and Fbg also decreased

from 551 ± 132 to 440 ± 107 mg/dl (P = 0.01 and P < 0.01, respectively).

We observed Sthe serial D/P-cre values in 18 patients. The changes in D/P-cre are shown in

Figure 1. No marked increase in D/P-cre s did not increase was observed after ≥2 years of combined

therapy and none of the . No patienpatients ts developed EPS during this study.(Fig. 1).

Discussion

Combined therapy with PD and HD corrected overhydration, with hiach was concomitant

manifested as a decrease in the number of antihypertensive medications drugs prescribed and the

level of ANP. In these patients, Wwe had already tried to use a 2.5% glucose solution or APD before

the initiation of combined therapy, but wtehey were unable to achieve adequate fluid control. We

used a 3.86% glucose solution only in a n emergency situations, such as acute congestive heart

failure, to avoid further because a long-term use of high-concentration glucose solutions may cause a

peritoneal damage. Therefore, combined therapy with PD and HD is a practical method for

controlling fluid status, without increasing the concentration of the glucose solution.

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Kawanishi et al. also reported that the combined therapy was able to control overhydration and

hypertensionthe body fluids and blood pressure, and also achieve adequate small solute clearances

(Kt/V > 2.0 weekly) [6]. Moreover, although the urine volume decreased, we found 2M, a middle-

molecule uremic toxin, also decreased significantly after combined therapy.

After the initiation of combined therapy, Hgb increased significantly from 7.9 ± 1.6 g/dl before

combined therapy to 10.7 ± 1.3 g/dl at 1 year after, though the dose of rHu-Epo decreased

significantly. EPO-resistant anemia has been demonstrated in overhydrated patientswith body fluid

control [17]. The decrease in hemodilution via the combined therapy should result in an increase in

Hgb level. However, we found the same phenomenon in six patients whose fluid status remained

unchanged after the combined therapy (9.3 ± 0.9 vs. 10.9 ± 0.9 g/dl, P = 0.01). Furthermore, we also

found a significant decrease in the EPO/Hgb ratio, which reflected EPO resistance, and a significant

increase in the reticulocyte count which reflected EPO resistance . Before after combined therapy

was initiated. TtThis result suggested that the combined therapy also improved EPO sensitivity. In

fact, several studies have suggested that underdialysis (especially the accumulation of middle-

molecule uremic toxin, e.g., 2M) is one of the main causes of EPO-resistancet anemia [18–21]. In

addition, the level of serum CRP has been reported to be a strong predictor of EPO resistance

[22,23], and combined therapy may significantly decrease inflammation those parameters. However,

iron status, administration of angiotensin-converting enzyme inhibitor or angiotensin 2 type 1

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receptor blockers, serum albumin level, and serum intact-parathyroid hormone levelsormone level

(237 ± 212 vs. 207 ± 222 pg/ml, P = 0.42, data not shown), which have also been reported as causes

of EPO resistance [24–26], did not change significantly change. Therefore, the marked improvement

of anemia after initiation of the combined therapy has probably might have resulted from the

combined effects of better body fluid control, better removal of uremic toxins, and improvement in

inflammation status. Since anemia is reported as an adverse prognostic factor in end-stage renal

failure [27,28], combined therapy may be a useful method for improving survival. In addition,

correction of anemia by combined therapy might improve the quality of life [29,30].

Although combined therapy permits substantial prolongation of PD, a risk exists of increasing the

incidence of EPS. The decrease in D/P-cre and IL-6 level in drainage, as shown after concomitant

use of HD, suggests a protective effect against chronic peritoneal damage via the combined therapy.

Konings et al. reported that peritoneal permeability is correlated with body fluid status [31], which

suggests that a histological improvement of peritoneal membrane edema may be partially involved

in the decrease in D/P-cre. On the other hand, in spite of former reports that D/P- cre was increasing

gradually with according to PD duration of PD and cumulative glucose exposure [32, 33], no marked

increase in D/P-cre was observed after ≥2 years of combined therapy. Therefore, with the decreased

IL-6 level in the drainage and the prolonged decrease in D/P-cre over several years, combined

therapy with PD and HD may circumvent not only overhydration, but also chronic peritoneal

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damage. Although the mechanisms by which peritoneal permeability and IL-6 level in the drainage

are reduced are not presently clear, the presence of periodical PD holidays, (which results in reduced

glucose exposure after starting combined therapy compared with PD alone, (approximately

500g/week vs. 700g/week, respectively.) [34]. , Improvement in adjustments in the status of body

fluids, and or increased removal of middle-molecule uremic toxin by HD, may also be involved. We

also showed that serum CRP decreased significantly decreased a after initiation of concomitant HD.

The mechanism involved is also not clear at present. However, a high CRP level has been reported as

a mortality risk factor (e.g., MIA syndrome [35–37]), and therefore a our findings suggesting that the

concomitant use of HD may lower mortality and morbidity in oliguric PD patients should be an

important one. The significant reduction in blood Fbg, an inflammation marker, might have been

induced by the decreased in protein losses from the peritoneum, which resulted from the PD

“holiday” and lower D/P-cre. However, rRegardless of the reason, Fbg per se is a risk factor for has

a negative effect on cardiovascular disorders such as atherosclerosis and thrombosis [38].

We previously reported that the frequency of EPS was 1.5% in patients with β 2M levels of <30

mg/L, andbut was >5.0% in those with β2M >30 mg/L, and suggested that β2M was useful as a

screening test for the onset of EPS, and that accumulation of β2M and other middle-molecular

uremic substances may be related to the pathophysiology of EPS [11, 39]. Therefore, we concluded

that the target level of β2M was <30 μg/ml. Thus, concomitant use of HD may be one way should be

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used to lower the level of β2M below this target level.

In the present study, urine volume and weekly urine CCr decreased significantly before and after

combined therapy. Our experience shows that the combined therapy may accelerate the decline

in the RRF, and we believe that this should be kept in mind in patients who still retain enough

RRF. It is necessary to note it for the combined patients who remain enough RRF. THIS IS

UNCLEAR

The present study had some limitations. First, this was not a randomized control study, and no

control patients were involved. Second, only a few (provide the number over the total)twenty-eight

of 53 patients had a follow-up of more than 2 years. Third, the maximum follow-up period was 8

years, and few patients were studied to evaluate mortality and morbidity. A longer mstudy with

larger numbers of patients in a multicenter study will be ore extended examination on a multi-

institutional basis is necessary to overcome these limitations.

Conclusions

We used concomitant once-weekly HD sessions in …(provide number)fifty-three PD patients

with overhydration and inadequate solute removal, andwith decreased RRF. Our findings The results

suggest that combined therapy with PD and HD is an effective approach modality to control

overhydration body fluid status and to correct inadequate solute removal, which leads to an

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improvement in renal anemia and inflammation. Although we observed no signs of found no

increase in the risk of EPS in these patientsis study, further longitudinal observation will be needed.

Conflict of interest

We have had no involvements that might raise the question of bias in the work reported or in the

conclusions, implications, or opinion stated.

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Figure legend

Figure 1. Yearly changes in D/P-cre in 18 patients who were followed for >2 years.

Before starting combined therapy, D/P-cre increased gradually in relation to PD duration. One year

after starting combined therapy, D/P-cre had a tendency to decrease, and no noticeable increase was

observed after ≥2 years of combined therapy.

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Table 1. Patient ProfilesGender (male/female) 40/13Age at the start of dialysis (years) 51±10 (29-69)Whole duration from the start of dialysis (months) 81±40 (13-208)Duration of PD at the start of combined therapy (months) 49±38 (0-184)Duration of combined therapy (months) 26±24 (6-113)Original kidney disease (number of patients) diabetic nephropathy 9 chronic glomerulonephritis 35 nephrosclerosis 6 unknown 3PD volume (ml/day) 8838±20172.5% glucose solution volume (ml/day) 3470±2894 (% vs. total volume) 53±31Total weekly CCr at the start of combined therapy (L/week) 50.2±5.3Urine weekly CCr at the start of combined therapy (L/week) 6.7±10.7Mean±SD or median (range) Abbreviation: PD, peritoneal dialysis

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Table 2. Clinical parameters indicating fluid status just before introduction of combined therapy (at start of study) and 1-year after introduction (after 1year)

At start of study After 1 year *P valueBody weight (kg) 62.6±11.3 61.1±12.9 <0.01Casual blood pressure (mmHg) systolic 145±22 138±17 0.03 diastolic 84±17 78±11 0.12Antihypertensive drugs (number) 2.6±1.4 2.1±1.4 <0.01Atrial natriuretic peptide (pg/ml) 123±104 60±50 <0.01Urine volume (ml/day) 253±405 123±331 <0.01Urine weekly CCr (L/week) 6.7±10.7 1.8±3.9 <0.01Ultrafiltration of PD (ml/day) 907±579 1008±383 0.17Mean ±SD or median (range)*Comparison between at start of study and after 1 yearNote: no patients used 3.86% glucose solution

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Table 3. Indicators of solute removal and other laboratory data just before introduction of combined therapy (at start of study) and 1-year after introduction (after 1year)

At start of study After 1 year *P valueBlood urea nitrogen (mg/dl) 61±16 59±13 0.11Serum creatinine (mg/dl) 13.5±3.6 12.7±3.1 <0.01Serum β2 microglobulin (μg/ml) 35.9±7.5 33.1±7.9 <0.01Serum albumin (mg/dl) 3.5±0.4 3.6±0.6 0.18Serum phosphate (mg/dl) 5.9±1.7 5.5±1.3 0.37Mean ±SD or median (range)*Comparison between at start of study and after 1 year

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Table 4. Clinical parameters indicating renal anemia just before introduction of combined therapy (at start of study) and 1-year after introduction (after 1year)

At start of study After 1 year *P valueHaemoglobin (g/dl) 8.2±1.6 10.7±1.2 <0.01Dose of rHu-erythropoietin (U/week) 5800±1349 4556±2058 <0.01 (U/week)/(g/dl hemoglobin) 698±257 357±244 <0.01Transferrin saturation (%) 24±13 29±13 0.08Ferritin (ng/ml) 139±120 138±157 0.74Reticulocyte count (%) 1.0±0.6 1.1±0.5 0.76 (×104/μl) 1.85±1.80 3.19±2.16 <0.01Mean ±SD or median (range)*Comparison between at start of study and after 1 year

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Table 5. Clinical parameters indicating fast PET and other risk factors of EPS just before introduction of combined therapy (at start of study) and 1-year after introduction (after 1year)

At start of study After 1 year *P valueD/P-cre 0.65±0.11 0.59±0.13 <0.01PET-drained volume (ml) 2464±192 2388±266 0.61PET-effluent fluid IL-6 (pg/ml) 21.0 (2.1-66.4) 10.3 (0.8-23.5) 0.03Serum C-reactive protein (mg/dl) 0.5 (0.01>-7.4) 0.2 (0.01>-0.6) 0.01blood fibrinogen (mg/dl) 551±132 440±107 <0.01Mean ±SD or median (range)*Comparison between at start of study and after 1 yearAbbreviations: PET, peritoneal equilibration test ; EPS, encapsulating peritoneal sclerosis; D/P-cre, Dialysate/Plasma creatinine ; IL-6, interleukin-6

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