Abstract

Background. Peritoneal transport rate, a major determinant of peritoneal dialysis (PD) patient survival, increases in most patients starting on PD, while in other patients peritoneal transport rate may decline. Although several factors may contribute to changes in peritoneal transport rate, inflammation is known to be associated with a high peritoneal transport rate, and residual renal function (RRF), which often declines after start of PD, may also be related to inflammation. Therefore, we hypothesized that changes in peritoneal transport rate during patients’ first year on PD and declining RRF may be linked with inflammation.

Methods. A total of 76 PD patients (40 males, mean age 56.8±14.1 years), who underwent two peritoneal equilibration tests at a mean of 0.4 months and 1 year after beginning PD, were included in the study. Based on the change in dialysate to plasma creatinine concentration ratio at 4‐h dwell (D/P Cr) during first year on PD, the patients were divided into decreased or unchanged (group DUC; n=22) and increased (group I; n=54) groups.

Results. Initially, group I had a lower proportion of high transporters and more often high serum C‐reactive protein (sCRP, ≥10 mg/l) and lower RRF compared with the DUC group. In group I, serum albumin and RRF decreased significantly and dialysate protein loss and glucose absorption increased significantly during the first year on PD. When patients were divided into two groups based on median change in RRF (1.9 ml/min), patients with a decrease in RRF >1.9 ml/min during first year on PD had a higher proportion of high sCRP, higher D/P Cr, and higher changes in D/P Cr compared to patients with a decrease in RRF ≤1.9 ml/min. Patients with elevated sCRP at one year included a higher proportion of patients who had high sCRP at the start of PD, higher increase in D/P Cr, lower serum albumin, lower RRF, and more decrease in RRF during first year on PD compared with patients having normal sCRP. RRF was inversely correlated with changes in D/P Cr during the first year on PD (r=−0.28, P=0.02). Multiple regression analysis revealed that the only factors affecting changes in D/P Cr were high sCRP and a low RRF.

Conclusions. Our preliminary short‐term study suggests that changes in peritoneal transport rate during patients’ first year on PD may be linked with inflammation and declining residual renal function. Inflammation and residual renal function were identified as the only independent factors determining peritoneal transport rate during the first year on PD. It is possible that inflammation may cause both an increase in peritoneal transport rate and a decline in residual renal function, or that the decline in residual renal function and the increase in peritoneal transport rate may induce or aggravate inflammation. Further studies are needed to confirm these findings.

Introduction

It is now well appreciated that peritoneal transport rates in peritoneal dialysis (PD) patients have a major impact on clinical management. Since Twardowski et al. [1] developed the standardized peritoneal equilibration test (PET), PET has been widely accepted as a useful method to assess an individual's peritoneal transport rate and to determine the optimal dialysis prescription and dose of dialysis. More recently, it has been reported that peritoneal transport rate, classified by PET, is a major determinant of patient survival [2,3].

However, peritoneal transport rate often changes after initiation of PD. Some studies have shown that in most patients peritoneal transport rate increases with time on PD [4,5], while others have found that peritoneal transport rate may decrease in some patients with time [5]. Finally, after initial early changes in peritoneal transport rate, the membrane function often is stable for up to three years [5,6]. Although the reasons for these discrepant results are not clear, mediators produced in the inflammatory process due to infection or bioincompatible PD solutions have been suggested to be involved in the regulation of the peritoneal membrane permeability, possibly resulting in alteration of the peritoneal transport rate [7]. One may expect that exposure to components in the PD solution increases in patients with high peritoneal transport rate, both because of the increased permeability of the peritoneal membrane and the need for increased use of hypertonic solutions, especially in patients with low residual renal function (RRF).

Moreover, it has been suggested that changes in renal function may be related to production of inflammatory mediators [8]. The deterioration of renal function and appearance of uraemia can be associated with a significant increase in serum cytokine levels in chronic renal failure and dialysis patients [9]. The RRF declines after the start of dialysis in most end‐stage renal disease patients and this might result in less efficient removal of inflammatory mediators, which could perhaps affect both the peritoneum and the kidney. The serum C‐reactive protein (CRP), which reflects the activity of pro‐inflammatory cytokines, has been used as a marker of inflammation. A recent study reported that CRP was inversely related to renal function [8]. Based on these observations it is possible that changes in peritoneal transport rate might be linked to inflammation and changes in RRF.

To test this hypothesis, we investigated changes in peritoneal transport rate and possible factors determining changes in the peritoneal transport rate during first year on PD to elucidate a possible relationship between changes in peritoneal transport rate, inflammation, and RRF.

Subjects and methods

Patients and study design

Between September 1990 and June 1999, 117 patients who were treated with PD at the Home Dialysis Unit affiliated with the Department of Renal Medicine, Huddinge University Hospital, Stockholm, Sweden, underwent a PET study within one month of PD according to the routine in the department. Of the 117 patients, the 76 patients who underwent two PETs, nutritional assessments, and biochemical analyses both at <1 month and at >6 months, at a mean of 0.4±0.2 months (range: 0.1–1.0 month) and 12.0±3.1 months (range: 6.1–17.7 months) after beginning PD, were included in the study. Forty patients were male and their mean age was 56.8 years (range: 29–85 years). The causes of renal failure in the 76 patients were chronic glomerulonephritis (n=26), diabetic nephropathy (n=16), interstitial nephritis (n=11), polycystic kidney disease (n=8), and other diseases or unknown aetiology (n=15).

Peritoneal equilibration test

The PET was performed as described by Twardowski et al. [1]. Briefly, a standard 4‐h dwell period was used, using a 2.27% glucose concentration for a 2‐l volume exchange. As glucose interferes with the assay for creatinine, the corrected value for creatinine was obtained by subtracting the glucose concentration multiplied by a correction factor (0.35) derived in our laboratory. The dialysate to plasma creatinine concentration ratio at 4‐h of dwell (D/P Cr; mean D/P±1 SD) was used to classify the patients as having a high, high average, low average, or low peritoneal transport rate. Based on the changes (1‐year value minus initial value) in D/P Cr during the first year on PD, the patients were divided into decreased or unchanged transport group (group DUC) and increased transport group (group I).

Residual renal function

RRF was estimated by calculating the average residual renal clearance of urea and creatinine. Based on the median value (1.9 ml/min) of changes in RRF during the first year on PD, the patients were divided into two groups: ΔRRF >1.9 ml/min and ΔRRF ≤1.9 ml/min.

Inflammation

Serum CRP was measured by using an immunonephelometric method for the assessment of inflammation. The patients were divided into two groups according to 1‐year CRP levels (normal range: <10 mg/l): CRP <10 mg/l and CRP ≥10 mg/l.

Body surface area

Body surface area was calculated using the Du Bois and Du Bois equation.

Biochemical analyses

A fasting venous blood sample was taken before the morning exchange. Blood chemistries were analysed by standard techniques. Serum albumin was determined by the bromcresol purple method.

Statistical analysis

Student's t‐test for paired and unpaired measurement or Kruskal–Wallis test were used to compare the differences between initial PET and 1‐year PET, and the differences in demographic and clinical variables between subgroups. Chi‐square test or Fisher's exact test was used to compare the nominal variables between subgroups. Spearman's rank correlation was used to determine the correlation between residual renal function and changes in peritoneal transport rate. Multiple regression analysis was used to identify the factors determining the changes in D/P Cr. Data are presented as means±SD. The difference was considered significant when the P value was less than 0.05.

Results

Comparison of PET results between initial study and 1‐year study in all patients

During the first year on PD, D/P Cr increased from 0.70±0.15 to 0.78±0.12 (P<0.001), D4/D0 glucose decreased from 0.45±0.12 to 0.39±0.09 (P<0.005), and net ultrafiltration decreased from 339±321 ml to 263±213 ml (P<0.06).

PET results in group DUC and group I during the first year on PD

During the first year on PD, 22 patients developed decreased or unchanged peritoneal transport rate (group DUC) and 54 patients developed increased transport rate (group I).

The PET results of the initial and 1‐year studies in the two groups are shown in Table 1. There were statistically significant differences in D/P Cr, D4/D0 glucose, and net ultrafiltration between group DUC and group I. Group I had lower initial D/P Cr, higher initial D4/D0 glucose, higher initial net ultrafiltration, higher 1‐year D/P Cr, and lower 1‐year D4/D0 glucose compared with group DUC. During the first year on PD, in group DUC, D/P Cr decreased and D4/D0 glucose and net ultrafiltration increased while in group I, D/P Cr increased and D4/D0 glucose and net ultrafiltration decreased.

Table 1.

PET results in the two groups according to classification of changes in D/P Cr during the first year on PD

 Decreased or Increased 
 unchanged transport 
 transport (n=54) 

 
(n=22)
 

 
Initial D/P Cr  0.85±0.12  0.63±0.13*** 
1‐Year D/P Cr  0.75±0.12###  0.80±0.12###
ΔD/P Cr −0.11±0.07  0.16±0.12*** 
Initial D4/D0 glucose  0.32±0.07  0.48±0.10*** 
1‐Year D4/D0 glucose  0.42±0.11###  0.37±0.07###
ΔD4/D0 glucose  0.10±0.09 −0.11±0.10*** 
Initial net ultrafiltration (ml)  116±259  432±299*** 
1‐Year net ultrafiltration (ml)  276±187#  258±224## 
ΔNet ultrafiltration (ml)  160±264 −174±322*** 
 Decreased or Increased 
 unchanged transport 
 transport (n=54) 

 
(n=22)
 

 
Initial D/P Cr  0.85±0.12  0.63±0.13*** 
1‐Year D/P Cr  0.75±0.12###  0.80±0.12###
ΔD/P Cr −0.11±0.07  0.16±0.12*** 
Initial D4/D0 glucose  0.32±0.07  0.48±0.10*** 
1‐Year D4/D0 glucose  0.42±0.11###  0.37±0.07###
ΔD4/D0 glucose  0.10±0.09 −0.11±0.10*** 
Initial net ultrafiltration (ml)  116±259  432±299*** 
1‐Year net ultrafiltration (ml)  276±187#  258±224## 
ΔNet ultrafiltration (ml)  160±264 −174±322*** 

Δ, Change in each variable during first year on PD.

*P<0.05, and ***P<0.0001 vs decreased or unchanged transport group by unpaired t‐test.

#P<0.05, ##P<0.0005, and ###P<0.0001 vs initial study by paired t‐test.

Comparisons of demographic variables between group DUC and group I

Demographic variables in the two groups are shown in Table 2. There was a statistically significant difference in the proportion of initially high transporters between the two groups. Group I initially had a lower proportion of high transporters.

Table 2.

Demographic variables according to change in D/P Cr during the first year on PD

 Decreased or Increased 
 unchanged transport 
 transport (n=54) 

 
(n=22)
 

 
Age (years) 55.8±14.3 57.2±14.2 
Time on PD (months) 12.4±2.7 11.8±3.2 
Male (%) 14 (63.6%) 26 (48.1%) 
Diabetes (%)  9 (40.9%) 11 (20.4%) 
CVD (%)  6 (27.3%) 10 (18.5%) 
APD at 1‐year assessment (%)  4 (18.2%)  8 (14.8%) 
Initially high transporter (%) 10 (45.5%)  1 (1.9%)*** 
 Decreased or Increased 
 unchanged transport 
 transport (n=54) 

 
(n=22)
 

 
Age (years) 55.8±14.3 57.2±14.2 
Time on PD (months) 12.4±2.7 11.8±3.2 
Male (%) 14 (63.6%) 26 (48.1%) 
Diabetes (%)  9 (40.9%) 11 (20.4%) 
CVD (%)  6 (27.3%) 10 (18.5%) 
APD at 1‐year assessment (%)  4 (18.2%)  8 (14.8%) 
Initially high transporter (%) 10 (45.5%)  1 (1.9%)*** 

CVD, cardiovascular disease; APD, automated peritoneal dialysis.

***P<0.0001 vs decreased or unchanged transport group.

Comparison of clinical variables between group DUC and group I

Clinical variables in the two groups are shown in Table 3. There were statistically significant differences in the proportion of patients with high serum CRP ≥10 mg/l, changes in serum albumin, changes in dialysate protein loss, changes in glucose absorption, RRF, and changes in RRF between the two groups. More often at the 1‐year test, the patients in group I had a high serum CRP and lower RRF compared with group DUC. In group I, serum albumin and RRF decreased significantly and dialysate protein loss and glucose absorption increased significantly during the first year on PD.

Table 3.

Clinical variables according to change in D/P Cr during first year on PD

 Decreased or Increased 
 unchanged transport 
 transport (n=54) 

 
(n=22)
 

 
Peritonitis episode during  5 (22.7%)  7 (13.0%) 
   first year (%)   
Initial serum CRP (≥10 mg/l) (%)  5 (22.7%) 21 (38.9%) 
Serum CRP at 1 year  5 (22.7%) 26 (48.2%)* 
   (≥10 mg/l) (%)   
Serum albumin (g/l) 31.2±3.9 32.1±5.1 
ΔSerum albumin (g/l) 1.8±3.9 −1.5±4.8** 
Dialysate protein loss (g/day) 5.8±1.7 6.0±1.8 
ΔDialysate protein loss (g/day) −1.2±3.1 0.7±2.3* 
Dialysate glucose used (mmol/day) 1258±726 1105±553 
ΔDialysate glucose used 472±624 360±562 
   (mmol/day)   
Glucose absorption (mmol/day) 594±270 580±219 
ΔGlucose absorption (mmol/day) 31±353 187±273* 
RRF (ml/min)  3.8±2.5  1.9±2.0*** 
ΔRRF (ml/min) −1.0±1.9 −2.1±2.9* 
Body surface area (m21.84±0.16 1.79±0.23 
 Decreased or Increased 
 unchanged transport 
 transport (n=54) 

 
(n=22)
 

 
Peritonitis episode during  5 (22.7%)  7 (13.0%) 
   first year (%)   
Initial serum CRP (≥10 mg/l) (%)  5 (22.7%) 21 (38.9%) 
Serum CRP at 1 year  5 (22.7%) 26 (48.2%)* 
   (≥10 mg/l) (%)   
Serum albumin (g/l) 31.2±3.9 32.1±5.1 
ΔSerum albumin (g/l) 1.8±3.9 −1.5±4.8** 
Dialysate protein loss (g/day) 5.8±1.7 6.0±1.8 
ΔDialysate protein loss (g/day) −1.2±3.1 0.7±2.3* 
Dialysate glucose used (mmol/day) 1258±726 1105±553 
ΔDialysate glucose used 472±624 360±562 
   (mmol/day)   
Glucose absorption (mmol/day) 594±270 580±219 
ΔGlucose absorption (mmol/day) 31±353 187±273* 
RRF (ml/min)  3.8±2.5  1.9±2.0*** 
ΔRRF (ml/min) −1.0±1.9 −2.1±2.9* 
Body surface area (m21.84±0.16 1.79±0.23 

Δ, Change in each variable during first year on PD. *P<0.05, **P<0.01, and ***P<0.005 vs decreased or unchanged transport group.

Comparison of clinical variables between patients with changes in RRF >1.9 ml/min and patients with changes in RRF ≤1.9 ml/min during the first year on PD

Clinical variables in the two different changes in RRF groups during the first year on PD are shown in Table 4. There were statistically significant differences in the proportion of patients with serum CRP ≥10 mg/l, D/P Cr, and changes in D/P Cr. The patients who had changes in RRF >1.9 ml/min during first year on PD had more often at 1‐year test a high serum CRP, higher D/P Cr, and higher changes in D/P Cr compared with patients who had changes in RRF ≤1.9 ml/min during the first year on PD.

RRF at 1‐year assessment was inversely correlated with changes in D/P Cr during the first year on PD (r=−0.28, P=0.02, n=76) (Figure 1).

Fig. 1.

Relationship between RRF at 1‐year on PD and changes in D/P Cr during first year on PD. RRF at 1‐year on PD was inversely correlated with changes in D/P Cr (r=−0.28, P=0.02, n=76).

Fig. 1.

Relationship between RRF at 1‐year on PD and changes in D/P Cr during first year on PD. RRF at 1‐year on PD was inversely correlated with changes in D/P Cr (r=−0.28, P=0.02, n=76).

Table 4.

Clinical variables according to change in RRF during first year on PD


 
ΔRRF >1.9 ml/min (n=36)
 
ΔRRF ≤1.9 ml/min (n=40)
 
Peritonitis episode during  3 (8.3%)  9 (22.5%) 
   first year (%)   
Initial serum CRP 15 (41.7%) 11 (27.5%) 
   (≥10 mg/l) (%)   
Serum CRP at 1 year 20 (55.6%)* 11 (27.5%) 
   (≥10 mg/l) (%)   
D/P Cr 0.81±0.11* 0.76±0.11 
ΔD/P Cr 0.11±0.15* 0.04±0.15 
Serum albumin (g/l) 31.7±5.5 31.9±4.1 
ΔSerum albumin (g/l) −0.7±4.9 −0.4±4.8 
Dialysate protein loss (g/day) 6.0±2.0 6.1±2.3 
ΔDialysate protein loss (g/day) 0.5±2.9 −0.08±2.5 
Dialysate glucose used 1211±629 1095±589 
   (mmol/day)   
ΔDialysate glucose used 461±642 331±517 
   (mmol/day)   
Glucose absorption (mmol/day) 592±204 578±257 
ΔGlucose absorption (mmol/day) 205±211 87±360 
Body surface area (m21.81±0.22 1.80±0.19 

 
ΔRRF >1.9 ml/min (n=36)
 
ΔRRF ≤1.9 ml/min (n=40)
 
Peritonitis episode during  3 (8.3%)  9 (22.5%) 
   first year (%)   
Initial serum CRP 15 (41.7%) 11 (27.5%) 
   (≥10 mg/l) (%)   
Serum CRP at 1 year 20 (55.6%)* 11 (27.5%) 
   (≥10 mg/l) (%)   
D/P Cr 0.81±0.11* 0.76±0.11 
ΔD/P Cr 0.11±0.15* 0.04±0.15 
Serum albumin (g/l) 31.7±5.5 31.9±4.1 
ΔSerum albumin (g/l) −0.7±4.9 −0.4±4.8 
Dialysate protein loss (g/day) 6.0±2.0 6.1±2.3 
ΔDialysate protein loss (g/day) 0.5±2.9 −0.08±2.5 
Dialysate glucose used 1211±629 1095±589 
   (mmol/day)   
ΔDialysate glucose used 461±642 331±517 
   (mmol/day)   
Glucose absorption (mmol/day) 592±204 578±257 
ΔGlucose absorption (mmol/day) 205±211 87±360 
Body surface area (m21.81±0.22 1.80±0.19 

Δ, Change in each variable during first year on PD.

*P<0.05 vs ΔRRF ≤1.9 ml/min.

Comparison of clinical variables between patients with high CRP (≥10 mg/l) and patients with normal CRP (<10 mg/l)

Table 5 shows clinical variables according to serum CRP at 1‐year on PD. More often at the initial test, patients with high CRP had a high serum CRP, higher changes in D/P Cr, lower serum albumin, lower RRF, and higher decline in RRF compared with patients having normal CRP.

Table 5.

Clinical variables according to serum CRP at 1‐year on PD

 Serum CRP Serum CRP 
 ≥10 mg/l <10 mg/l 

 
(n=31)
 
(n=45)
 
Peritonitis episode during first  8 (24.2%)  4 (9.3%) 
   year (%)   
Initial serum CRP (≥10 mg/l) (%) 20 (64.5%)**  6 (13.3%) 
D/P Cr 0.79±0.12 0.78±0.12 
ΔD/P Cr 0.14±0.16* 0.05±0.16 
Serum albumin (g/l) 30.5±5.5* 32.6±4.1 
ΔSerum albumin (g/l) −1.2±4.9 −0.07±4.8 
Dialysate protein loss (g/day)  5.9±2.0  6.2±2.2 
ΔDialysate protein loss (g/day) −0.3±2.9  0.5±2.5 
Dialysate glucose used (mmol/day) 1130±506 1161±670 
ΔDialysate glucose used (mmol/day)  322±447  438±652 
Glucose absorption (mmol/day)  585±173  584±266 
ΔGlucose absorption (mmol/day)  153±219  135±352 
RRF (ml/min)  1.7±1.7*  2.8±2.4 
ΔRRF (ml/min) −2.6±2.2* −1.5±2.5 
Body surface area (m21.85±0.24 1.77±0.19 
 Serum CRP Serum CRP 
 ≥10 mg/l <10 mg/l 

 
(n=31)
 
(n=45)
 
Peritonitis episode during first  8 (24.2%)  4 (9.3%) 
   year (%)   
Initial serum CRP (≥10 mg/l) (%) 20 (64.5%)**  6 (13.3%) 
D/P Cr 0.79±0.12 0.78±0.12 
ΔD/P Cr 0.14±0.16* 0.05±0.16 
Serum albumin (g/l) 30.5±5.5* 32.6±4.1 
ΔSerum albumin (g/l) −1.2±4.9 −0.07±4.8 
Dialysate protein loss (g/day)  5.9±2.0  6.2±2.2 
ΔDialysate protein loss (g/day) −0.3±2.9  0.5±2.5 
Dialysate glucose used (mmol/day) 1130±506 1161±670 
ΔDialysate glucose used (mmol/day)  322±447  438±652 
Glucose absorption (mmol/day)  585±173  584±266 
ΔGlucose absorption (mmol/day)  153±219  135±352 
RRF (ml/min)  1.7±1.7*  2.8±2.4 
ΔRRF (ml/min) −2.6±2.2* −1.5±2.5 
Body surface area (m21.85±0.24 1.77±0.19 

Δ, Change in each variable during first year on PD.

*P<0.05, and **P<0.0001 vs ΔRRF ≤1.9 ml/min.

Factors determining the changes in D/P Cr

Determinants of changes in D/P Cr among 12 variables, including age, time on PD, gender, the presence of diabetes, cardiovascular disease, peritonitis episode, serum CRP, serum albumin, dialysate glucose used, glucose absorption, RRF, and body surface area, are shown in Table 6. Multiple regression analysis revealed that the factors determining the changes in D/P Cr were high serum CRP and a low RRF.

Table 6.

Predictor of the change in D/P Cr (stepwise multiple regression analysis)


 
B
 
SE
 
T ratio
 
Serum CRP (≥10 mg/l  0.04 0.02  2.38* 
   vs <10 mg/l)    
RRF −0.02 0.008 −1.98* 
 F=5.27**   
 Adjusted r2=0.11   

 
B
 
SE
 
T ratio
 
Serum CRP (≥10 mg/l  0.04 0.02  2.38* 
   vs <10 mg/l)    
RRF −0.02 0.008 −1.98* 
 F=5.27**   
 Adjusted r2=0.11   

*P<0.05, **P<0.01.

Discussion

This preliminary short‐term study shows that during the initial year on PD, changes in peritoneal transport rate appeared to be linked to inflammation (high serum CRP) and changes in RRF. Patients with an increased peritoneal transport rate more often had high serum CRP, lower RRF, and significant decreases in serum albumin and RRF. Furthermore, the reduction in RRF was more marked in patients with signs of inflammation. Finally, high serum CRP and low RRF were the only identified predictors of increased peritoneal transport rates.

It is well recognized that peritoneal transport rate changes with time on PD with some differences between the studies [4,5]. For example, Davies et al. [10] found a significant increase in D/P Cr after 6 months on PD compared to initial results obtained within 1 month of commencing PD. Struijk et al. [11] reported a significant decrease in solute transport after 5 months on PD compared with initial values obtained within 3 months after the start of PD. Blake et al. [5] observed an increase in 20% of patients, a decrease in 3% of patients, and unchanged peritoneal transport rate in 77% of patients between 6 and 12 months on PD. In the present study, peritoneal transport rate increased in the majority of patients during the first year on PD whereas peritoneal transport rate decreased or was unchanged in 29% of the patients. A difference between our study and previous studies is that we included only those patients who were investigated initially and after one year of PD.

Although the factors contributing to changes in peritoneal transport rate during the first year on PD are not clear, in the present study, changes in peritoneal transport rate were strongly correlated with high serum CRP, and patients with increased peritoneal transport rate had decreased serum albumin and increased dialysate protein loss. It is generally accepted that peritoneal transport rate depends on both effective peritoneal surface area and permeability [7]. Many of the mediators produced in the inflammatory process can affect microvascular permeability and vascular tone [12]. Of note is that serum CRP reflects the activity of pro‐inflammatory cytokines [8] and serum CRP and dialysate albumin loss are main determinants of serum albumin [13]. Serum albumin is, perhaps erroneously, often used as a marker for nutrition in PD patients. In the present study, although the origin of inflammation at start of PD was not clear and D/P Cr was not different between two CRP groups, our finding of a strong relationship between changes in peritoneal transport rate and serum inflammatory markers suggests that a state of inflammation may affect changes in peritoneal transport rate during the first year of PD.

In addition to this relationship, our study reveals that changes in peritoneal transport rate were strongly correlated with RRF. Patients with an increased peritoneal transport rate had lower RRF as well as a more marked decline of RRF during the first year of PD. Similar findings have been described by Davies et al. [6], who reported that solute transport was stable in patients with stable RRF, resulting in a lesser requirement of hypertonic glucose exchanges in these patients [6]. This may suggest that changes in peritoneal transport rate could be related to intraperitoneal glucose or other components in the dialysis fluid. In the present study, we found no significant relationship between changes in peritoneal transport rate, amount of dialysate glucose used, and glucose absorption amount. In the patients with changes in RRF >1.9 ml, three patients used icodextrin solution and seven patients were treated with APD whereas in the patients with changes in RRF ≤1.9 ml, five patients were also treated with APD. This may explain why there was no major difference in the amount of dialysate glucose used and glucose absorption amount between the two groups.

On the other hand, there may also be an association between renal function and inflammatory mediators [14,15]. Brockhaus et al. [14] found that in uraemic non‐dialysed patients, plasma levels of soluble tumour necrosis factor (TNF) receptors increased progressively with declining renal function. Herbelin et al. [15] reported that plasma interleukin (IL)‐6 activity was significantly increased in patients with chronic renal failure compared to its level in normal individuals. This suggests that renal failure per se may contribute to the inflammatory response with elevated serum levels of pro‐inflammatory cytokines. Indeed, reduced renal function may affect both TNF [16] and IL‐1 [17] clearance in nephrectomized rats. The importance of the kidney in cytokine handling is further underscored by Hession et al. [18] who demonstrated that the Tamm–Horsfall glycoprotein might function as a unique renal regulatory glycoprotein that regulates the activity of potent cytokines, such as IL‐1 and TNF. Therefore, our finding of a negative correlation between changes in peritoneal transport rate and RRF may suggest that a reduction in renal function may aggravate an inflammatory state due to decreased renal clearance of cytokines [14,15] and that this may increase the peritoneal transport rate [12].

The association between reduction in RRF and high serum CRP in the present study is in agreement with some previous reports [19,20], indicating a detrimental role of inflammation on RRF. Shin et al. [19] reported that peritonitis rate was an independent risk factor for the declining RRF, resulting in release of cytokines during the inflammatory process. Rottembourg [21] proposed that a rapid decline of RRF in HD patients may be related to nephrotoxic effects of the inflammatory mediators generated by extracorporeal circulation. In a previous study [22], we found that there were significant inverse correlations between serum hyaluronan concentration and RRF, and between serum TNF‐α and RRF. On the other hand, it is also possible that fluid overload, resulting from reduction in RRF, may cause inflammation [23].

In contrast to previous research [6], in the present study, peritoneal transport rate was not related with body surface area. Davies et al. [6] reported that at 6 months of PD there was a strong correlation between D/P Cr and body surface area. However, in the present study, there was no difference in body surface area between the two groups and no correlation between body surface area and changes in peritoneal transport rate.

In conclusion, our preliminary short‐term study suggests that peritoneal transport rate during patients’ first year on PD may be linked with inflammation and declining RRF. In fact, inflammation and RRF were identified as the only independent factors determining peritoneal transport rate during the first year on PD. It is possible that inflammation may cause both an increase in peritoneal transport rate and a decline in RRF, or that the decline in RRF further aggravates inflammation due to less efficient removal of cytokines. On the other hand, it cannot be ruled out that the decline in RRF and the increase in peritoneal transport rate may result in changes (fluid overload or increased use of hypertonic glucose solutions?) that might aggravate inflammation. Further long‐term prospective studies are needed in this area.

Deceased.

Correspondence and offprint requests to: Bengt Lindholm, MD, PhD, Divisions of Baxter Novum and Renal Medicine, K 56 Huddinge University Hospital, SE‐141 86 Huddinge, Sweden. Email: bengt.lindholm@klinvet.ki.se

This work was presented in part at the 4th European Peritoneal Dialysis Meeting, April 16–18, 2000, Madrid, Spain. We thank Ms Ewa Nell, Ms Solveig Nordlöf, Ms Vreni Fröhlich, and Ms Marie‐Louise Sjöstrand‐Flinta for skilful technical assistance. This study was supported by a grant from Baxter Healthcare Corporation, McGaw Park, Illinois, USA, and Martin Rind Foundation (OH).

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