Factors influencing peritoneal transport parameters during the first year on peritoneal dialysis: peritonitis is the main factor

Gloria del Peso1, María José Fernández-Reyes2, Covadonga Hevia1, María Auxiliadora Bajo1, María José Castro1, Antonio Cirugeda3, José Antonio Sánchez-Tomero3 and Rafael Selgas1

1 Department of Nephrology, University Hospitals La Paz, 2 General Hospital, Segovia and 3 La Princesa, Madrid, Spain

Correspondence and offprint requests to: Gloria del Peso, MD, Servicio de Nefrología, Hospital Universitario La Paz, Po Castellana 261, E-28046-Madrid. Spain. Email: gpeso.hulp{at}salud.madrid.org



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. Studies on the evolution of peritoneal transport during the first year of peritoneal dialysis (PD) are scarce and their results are contradictory. The aim of the present study was to analyse the evolution of peritoneal transport and residual renal function during the first year on PD, and to determine the factors that may influence them.

Methods. We studied 249 patients on continuous ambulatory PD with glucose exchange solutions (117 men, 132 women, mean age 51.9±16 years) 59 of whom had diabetes (25 type I). At baseline and after 1 year, we determined the mass transfer coefficients of urea (U-MTAC) and creatinine (Cr-MTAC), net ultrafiltration and residual renal function.

Results. Residual renal function decreased significantly during the first year (from 3.9±2.8 to 2.4±2.2 ml/min, P<0.001). Both U-MTAC and Cr-MTAC decreased after 1 year [U-MTAC from 22.7±7.8 to 20.7±6.6 ml/min (P<0.001), Cr-MTAC from 10.5±5.3 to 10.1±4.6 ml/min (NS)]. The ultrafiltration capacity increased significantly (from 923±359 to 987 U 341 ml/4 h, P<0.001). The evolution of MTAC values was independent of age, sex, diabetes and amount of hypertonic glucose used. When patients were grouped according to their initial Cr-MTAC, we observed a tendency toward normalization of the parameters of peritoneal function. Patients with peritonitis (n = 88) showed a first year increase in Cr-MTAC, which was significantly higher than in patients without peritonitis (11.1±5 vs 9.5±4.2, P<0.01). Ultrafiltration decreased in patients with more than four accumulated days of peritonitis (from 1062±447 to 1024±340 ml/4 h, NS); it increased in patients without peritonitis.

Conclusions. The peritoneal transport parameters tended toward normalization during the first year on PD, mainly with a decrease of small solute transport and an increase of ultrafiltration capacity. This evolution is independent of age, gender, diabetes and higher exposure to glucose in PD solutions. Peritonitis was the only independent factor that affected peritoneal function during the first year on peritoneal dialysis.

Keywords: peritoneal dialysis; peritoneal transport; peritonitis; ultrafiltration



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Water and small solute transport in peritoneal dialysis (PD) patients changes with time on PD, and varies between individuals. Approximately 80% of patients on PD maintain stable peritoneal function. Some long-term PD patients show an increase in the peritoneal transport of small molecules and a decrease of their ultrafiltration (UF) rates [1,2]. Few studies have been focused on the changes of peritoneal transport during the first year on PD, and the available results are controversial. Some authors have found an initial increase of peritoneal transport of small solutes and a concomitant decrease of UF during the first year [3,4], while others have described a significant decrease in solute transport during the first months on PD [5].

It has been reported that a high peritoneal transport when starting PD determines higher medium- to long-term morbidity and mortality [6–8], but here too there is still some controversy. Some authors [9] believe that volume status in the context of impaired UF capacity, but not a high transport status, is responsible for the diminished technique and patient survivals.

The aims of the present study were: (i) to analyse the evolution of peritoneal transport parameters during the first 12 months on continuous ambulatory peritoneal dialysis (CAPD) and to investigate the factors related to it; and (ii) to study the course of patients with a high transport or low UF rate, or both, at baseline.



   Subjects and methods
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
We evaluated 382 patients who were treated by PD between 1980 and 2001. Of them, 16 were censored because of renal transplantation (n = 10), transfer to haemodialysis (n = 4), death (n = 1) or recovery of renal function (n = 1) during the first year of follow-up. Additional patients were not included in the final analysis because a kinetic study at 12 months was not possible in them (n = 62), or because they were treated with icodextrin during the first year on PD (n = 55). In all, we analysed 249 patients who had at least two peritoneal transport studies: at baseline (between 15 and 45 days after the initiation of CAPD) and after 12 months on CAPD.

We performed a peritoneal transport kinetic study, consisting of a 4 h dwell time glucose exchange, and the taking of six peritoneal effluent samples (at 0, 30, 60, 120, 180 and 240 min) and one blood sample to calculate the peritoneal mass transfer area coefficient of urea (U-MTAC, ml/min) and creatinine (Cr-MTAC, ml/min) using a previously described [10] mathematical model. This coefficient represents the isolated diffusive capacity of the membrane under theoretically infinite dialysate flow. The patients fasted during each functional study, and they received no drugs except low doses of subcutaneous insulin, if necessary. The kinetic study was done at least 30 days after any episode of peritonitis. The presence of peritoneal inflammation was determined by performing cell counts on the peritoneal effluent, and peritonitis was defined as the presence of >100 white blood cells/µl with >50% polymorphonuclear cells. Net UF rate (ml) was estimated by the net negative balance (weighing the bag after drainage), using a 2 l 3.86% glucose exchange during 4 h of dwell time. This value represents mostly the convective transport capacity. Residual renal function (RRF, ml/min) was estimated by the average of the renal urea and creatinine clearances.

In order to distinguish the evolution of the different parameters according to the type of peritoneal transport at baseline, we established five transport categories, according to the quintile distribution of the patients’ initial Cr-MTAC, as follows: 1st quintile, Cr-MTAC <6.7; 2nd quintile, Cr-MTAC 6.7–8.6; 3rd quintile, Cr-MTAC 8.61–10.7; 4th quintile, Cr-MTAC 10.71–13.5; and 5th quintile, Cr-MTAC >13.5. The correspondence between creatinine peritoneal equilibration test and MTAC quintiles is as follows: low transporters (<6.7 ml/min), low-average (6.71–8.6 ml/min), high-average (8.61–10.7 ml/min) and high transporters (>10.71 ml/min). For the last group, we distinguish between high and very high (>13.5 ml/min) in order to establish differences that facilitate the analysis.

In addition, we analysed separately the patients who had UF failure at baseline (n = 12), as defined by Ho-dac-Pannekeet et al. [11]. The amount of glucose exchange solutions used was registered every month, and then it was averaged for the entire year. Excess use of hypertonic glucose was defined as the use of >25% of the total volume of dialysate of 3.86% glucose exchange solutions per day or >50% of 2.27% glucose solutions per day.

Statistical analysis
Values are expressed as the mean±SD, and a P<0.05 was considered statistically significant. The {chi}2 test was used to compare proportions, and the Student t-test to compare means. A two-way repeated measures analysis of variance (ANOVA) was used. A ‘post hoc’ test was performed using the Bonferroni approach.



   Results
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
All patients
We studied 249 patients (47% men, 53% women) with a mean age of 51.9±16 years (range 10–85). Of them, 24% had diabetes (25% of them type I diabetes mellitus). Their primary kidney diseases were: diabetic nephropathy in 54 patients, tubulo-interstitial nephritis in 50, chronic glomerulonephritis in 36, nephroangiosclerosis in 34, systemic in 25, polycystic renal disease in 19, vascular in seven, hereditary in three, other in two and unknown in nine. All patients were treated with CAPD and used glucose-based dialysis solutions during the study. Of the cohort, 34 patients (13.6%) used an excess of glucose dialysis solutions during the first year on CAPD. In all, 88 patients (35%) had some episode of peritonitis during their first year on CAPD, with a mean of 5.9±4.6 days of peritoneal inflammation (range 1–25); 49 patients had >4 accumulated days of peritonitis during the study period. No patient received icodextrin.

During the first year on CAPD, the peritoneal transport of low molecular weight solutes decreased and the UF rate showed a significant increase (Table 1). There was an inverse linear correlation between Cr-MTAC and UF at the beginning of treatment (r = –0.14, P = 0.019) and their values after 12 months (r = –0.24, P = 0.000). No significant differences in the evolution of peritoneal transport were found when adjusted for age, gender or diabetes status. Men started CAPD with significantly higher U-MTAC than women (23.7±8.3 vs 21.8±7.2, P = 0.046). Both sexes showed the same tendency in the evolution of peritoneal function parameters (data not shown). There were no differences between diabetic and non-diabetic patients in the evolution of peritoneal parameters: U-MTAC decreased in both groups (from 24.1±7 to 22.4±6 in diabetics, and from 22.3±8 to 20.2±6 in non-diabetics, NS), as did Cr- MTAC (from 11±5 to 10.5±4 in diabetics, and from 10.3±5 to 10±4.7 in non-diabetics, NS). UF capacity increased both in diabetics (from 957±349 to 995±332) and in non-diabetics (from 913±363 to 987±343), but no significant differences were found between them.


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Table 1. The evolution of the parameters of peritoneal function during the first year on CAPD

 
Grouped according to initial Cr-MTAC
When we analysed the results according to the Cr-MTAC at baseline (Figure 1), we observed a regression-to-mean phenomenon of peritoneal transport parameters. Patients with MTAC-Cr >13.5 at baseline (5th quintile) showed a significant decrease of U-MTAC and Cr-MTAC. In contrast, patients with the lowest basal Cr-MTAC (1st quintile) had significant increases of both MTAC values after the first year. A significant increase of UF capacity and a decrease of RRF were found in all groups, with no differences between the different groups.



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Fig. 1. The parameters of peritoneal function according to the initial Cr-MTAC category. 1st quintile, Cr-MTAC <6.7; 2nd quintile, Cr-MTAC 6.71–8.6; 3rd quintile, Cr-MTAC 8.61–10.7; 4th quintile, Cr-MTAC 10.7–13.5; and 5th quintile, Cr-MTAC >13.5. The P-value expresses the differences between groups in the comparison of the gradients. Post hoc analysis of U-MTAC showed statistically significant (P<0.05) differences when each subgroup is compared with each of the others, except for 1st vs 2nd quintile, 2nd vs 3rd, 2nd vs 4th and 3rd vs 4th. Post hoc analysis of Cr-MTAC showed statistically significant differences (P<0.05) when each subgroup is compared with each of the others, except for 3rd vs 4th quintile.

 
Patients with initial UF failure
Of the cohort, 12 patients (4.8%) started CAPD with UF failure and their UF capacity increased significantly after the first year on CAPD (from 312.5±77.2 to 575 ±246 ml, P = 0.005). Both U-MTAC (from 26.7±8.9 to 21.1±7.6, P = 0.06) and Cr-MTAC (from 15.1±4.8 to 11.2±4.5 ml/min, P<0.041) decreased during this period, as did their RRF (from 4.5±2.4 to 3.3±2.7 ml/min, P<0.07). Only two patients remained with UF failure at the end of the year.

Excess use of hypertonic glucose solutions
Except for a significantly higher decrease of RRF in those who used an excess of hypertonic glucose (from 4.3±2.9 to 2.1±1.6 vs 3.8±2.7 to 2.4±20.3, P = 0.035), we found no correlation between the excess use of hypertonic glucose solutions and the evolution of peritoneal function parameters.

Influence of peritonitis
The characteristics of patients with and without peritonitis are shown in Table 2. The evolution of U-MTAC and RRF was not significantly different in patients with or without peritonitis during the first year on CAPD (Figure 2). The Cr-MTAC decreased in the patients without peritonitis, while the patients who had some episodes of peritonitis showed an increase of Cr-MTAC, which was higher in patients with >4 accumulated days of peritonitis. These differences were not statistically significant. However, there was a significant difference in Cr-MTAC values after the first year between the patients with and without peritonitis (11.1±5 vs 9.5±4.2, P<0.01). The patients with >4 days of peritonitis showed no significant change in UF capacity, in contrast to the increase of UF capacity found in patients who had <4 days of, or no, peritonitis.


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Table 2. The characteristics of patients with and without peritonitis

 


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Fig. 2. The parameters of peritoneal function of patients without peritonitis, and of those with less, or more, than 4 days of peritonitis. The P-value expresses the differences between groups in the comparison of the gradients. None of the parameters showed significant differences when patients with and without peritonitis were compared. *P = 0.037 when comparing patients with <4 days of peritonitis with those with a total of >4 days of peritonitis.

 


   Discussion
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
During the first year on CAPD, we found a tendency for low molecular weight solute transport to decrease and UF capacity to increase. UF failure is one of the major causes of drop-outs among PD patients. It has been reported that some long-term PD patients lose UF capacity and develop an increase in small solute transport [3,5]. Those changes in peritoneal kinetics appear after the second or third years of treatment. However, the peritoneal membrane function of most patients remains stable with time on PD [1,2]. In the study by Selgas et al. [1], 80% of patients showed mild or no changes in peritoneal function during PD. Blake et al. [2] observed that >70% of patients maintain a stable peritoneal function at 12 months, while only 3% show a decrease in D/P creatinine. Differing follow-ups and variability in the definition of peritoneal membrane failure may be the reasons for these discrepancies. The results of short-term studies are still controversial. Our findings agree with those of some previous studies [5,12], but conflict with others [2–4]. Struijk et al. [5] reported that, 4 months after the beginning of PD, the patients showed lower net UF and higher small solute transport than in the first month. In contrast, Davies et al. [3] found a significant increase of D/P creatinine, associated with a loss of UF capacity after 6 months on PD, and a stabilization of parameters of peritoneal function during the next 30 months. Chung et al. [4] have described the initial increase in D/P creatinine and the concomitant decrease in net UF after the first year on PD in >70% of patients. All these studies have employed the D/P creatinine ratio to analyse peritoneal transport kinetics, a less sensitive marker than the MTAC value used in our study. In addition, we analysed the evolution over time of peritoneal transport separately, according to its baseline status. When we took into account the initial Cr-MTAC, we found a trend towards a normalization of peritoneal transport parameters during the first 12 months on CAPD, independently of the initial status. Moreover, the group of patients with the highest transport at the beginning of treatment (Cr-MTAC >13.5) showed a significant decrease of small molecule transport and also an increase of UF capacity during the first year on CAPD. This may indicate an initial adaptation of the peritoneal membrane to PD fluids with a decrease of vascular surface area. Davies et al. [13] have previously reported that longitudinally the changes over time in solute transport vary according to the initial status of transport. They observed that the increase in solute transport occurs mainly in patients with low transport at baseline. Lo et al. [12] obtained similar results. They found a decrease in solute transport in high transport patients, but an increase in initially low transporters. The higher rate of drop-outs from PD among high transporters has been proposed as the possible reason for the tendency of small solute transport to increase.

There is agreement on the fact that the loss of UF capacity increases with time on PD. The main factor associated with the decrease of UF capacity is the increase in small solute transport. As shown in Figure 1, the patients from all groups showed a significant increase in UF capacity during the first 12 months, independently of their type of peritoneal transport at baseline. In addition, the patients with UF failure at baseline (UF <400 ml/4 h 3.86%) also showed a significant increase of UF capacity during the year, with only two patients remaining with UF failure after the year. We have found that significant inter-patient differences exist, but we believe that a water transport abnormality manifest when beginning PD does not always presage subsequent UF failure. However, longer follow-ups of these patients are needed to confirm our findings. An adaptative process during the early stages of the treatment takes place in PD patients, with a decrease or increase of peritoneal surface area, depending on the number of capillaries perfused during the contact of dialysis solutions with the peritoneal membrane. Our results lead us to hypothesize that the first year is a stage during which adaptation occurs to the vasoactive processes that occur during PD. The PD patients whose UF failure persisted after the first year are those with inherent UF failure, and they reflect the true inability of the peritoneum to adapt, in their cases, to the glucose of the dialysate.

When we analysed the possible causes of the changes in peritoneal transport, we analysed the main risk factors described, such as chronic exposure to bioincompatible dialysis solutions and peritonitis. Since we included in the study only patients treated with glucose exchange solutions, a selection bias cannot be excluded. Glucose has been described as the main cause of peritoneal damage [14]; however, a vicious circle exists, because higher solute transport induces higher use of hypertonic glucose exchange solutions, and this also induces higher small solute transport. In the present study, the amount of glucose used was not related to changes in peritoneal transport during the first year on CAPD. It is possible that the follow-up was too short to reveal the functional changes that are expected to occur after prolonged exposure to high concentrations of glucose. In contrast to our findings, Davies et al. [15] have found that early exposure to large amounts of hypertonic glucose solutions preceded the functional abnormalities of the peritoneum in long-term PD patients. Previous studies reported by Selgas et al. [16] showed that the patients who developed early UF failure had a higher prevalence of diabetes and also had larger glucose loads since their second years on PD than the patients who did not. Similar findings have been reported by Chung et al. [4], with a direct correlation between the amount of glucose in the dialysate and changes in peritoneal transport. In our series, water and small solute transport showed no correlation with diabetes status. It has been stated that diabetics have higher solute transport [17,18] in association with a higher effective surface area [19], but in the present study whether or not a patient had diabetes did not influence the subsequent evolution of peritoneal transport. This may indicate only that diabetic changes do not appear early in the evolution. However, diabetics showed higher initial RRF and higher loss of RRF during the first year on CAPD, a loss that may be due to their starting on PD earlier.

In our series, the most important factor influencing the short-term peritoneal kinetics was the presence of peritonitis, which during the first year on CAPD had a deleterious effect on the peritoneal transport of water and small solutes. The patients with some peritonitis, in contrast to those without, showed an increase of Cr-MTAC. This indicates that, in the early stages of PD, inflammation may have induced structural changes in the peritoneum, such as an increase of the effective vascular surface area, which alters peritoneal small solute transport. In contrast, the impact of peritonitis on water transport was only detected in patients with >4 accumulated days of peritonitis. These findings concur with those obtained in long-term PD patients [3,10]. Blake et al. [2] previously have reported the association between peritonitis and an increase of peritoneal transport. Fußholler et al. [20] have also found that patients with histories of peritonitis showed an increased small solute transport. However, when they considered the incidence of peritonitis, no significant differences were found when comparing that group with those who had no peritonitis. In addition, as previously described [3], we too have found that the severity of peritoneal inflammation shows a direct relationship to the degree of the functional alteration.

In summary, there is a tendency toward normalization in peritoneal transport parameters during the first year on CAPD, mainly a decrease of small solute transport and an increase of UF capacity. These initial peritoneal changes are mainly influenced by peritonitis, but not by an early exposure to higher amounts of glucose in PD solutions.

Conflict of interest statement. None declared.



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 8. 6.04
Accepted in revised form: 12. 1.05