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NDT Advance Access originally published online on December 19, 2005
Nephrology Dialysis Transplantation 2006 21(4):1032-1039; doi:10.1093/ndt/gfi344
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Original Articles: Dialysis and Transplantation

Evaluation of peritoneal transport properties at onset of peritoneal dialysis and longitudinal follow-up

Gaëtan Clerbaux1, Julie Francart2, Pierre Wallemacq3, Annie Robert2 and Eric Goffin1

1 Department of Nephrology, 2 Department of Epidemiology and Biostatistics and 3 Department of Medical Biology, Université Catholique de Louvain, Brussels, Belgium

Correspondence and offprint requests to: Prof. Eric Goffin, Department of Nephrology, UCL Medical School, 10 Avenue Hippocrate, B-1200 Brussels, Belgium. Email: goffin{at}nefr.ucl.ac.be



   Abstract
Top
 Abstract
Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. The clinical determinants of baseline peritoneal membrane (PM) transport characteristics, as evaluated by a hypertonic peritoneal equilibration test (PET), remain ill-defined. Likewise, the longitudinal evolution of PM transport properties in peritoneal dialysis (PD) patients given automated PD (APD) and icodextrin still needs to be determined precisely. The aims of the present study were (1) to determine the clinical and biological factors affecting PM transport characteristics at PD onset and (2) to assess the longitudinal evolution of these markers.

Methods. Seventy-two consecutive patients performed a baseline 3.86% glucose dialysate PET and were enrolled. Subgroups of 35 and 18 patients underwent another PET 1 and 2 year(s) later, respectively, and were included in the longitudinal part. For each patient, clinical and biological data were reviewed and PM transport markers calculated.

Results. At onset of PD, angiotensin-converting enzyme (ACE) inhibitor intake (r = 0.31, P = 0.01), presence of a diabetes (r = 0.26, P = 0.03) and body surface area (BSA) (r = 0.26, P = 0.03) independently affected the mass transfer area coefficient (MTAC) of creatinine. Serum albumin (r = –0.46, P<0.001) and net ultrafiltration (r = –0.33, P = 0.009) inversely correlated with MTAC creatinine. Sodium sieving was inversely correlated with BSA (r = –0.33, P = 0.01). Serum albumin also inversely correlated with albumin clearance (r = –0.39, P = 0.02). Finally, the independent covariates that affected {alpha}2-macroglobulin clearance were age (P = 0.03), diabetes (P = 0.01) and the level of residual renal function (P<0.01). Serum albumin decreased with time on PD (P = 0.02). A rise in small solute transport and a decrease in net ultrafiltration, but no change in protein clearances, were also observed after 2 years of PD.

Conclusions. Transport properties across the PM, as evaluated by MTAC creatinine and sodium sieving determinations, are correlated with anthropometric characteristics (BSA) and by comorbid conditions (witnessed by the presence of diabetes, a low serum albumin concentration and the prescription of an ACE inhibitor). The short-term evolution (2 years) of the PM transport properties of patients on APD and icodextrin is still characterized by a progressive increase in small solute transport and a loss of ultrafiltration capacity, as documented in ancient studies, but not with a modification in protein clearances. This conclusion merits, however, to be further evaluated in a larger cohort of PD patients after a longer follow-up.

Keywords: angiotensin-converting enzyme inhibitors; body surface area; icodextrin; mass transfer area coefficient of creatinine; peritoneal equilibration test; sodium sieving



   Introduction
Top
 Abstract
 Introduction
Subjects and methods
 Results
 Discussion
 References
 
Peritoneal dialysis (PD) is currently used in ~15% of the worldwide dialysis population [1]. Infectious peritonitis and alteration of the peritoneal membrane (PM), with ultrafiltration (UF) failure as a consequence, are the major causes of PD technical failure. Classically, the PM function is assessed by a peritoneal equilibration test (PET), as originally described by Twardowski et al. [2]. This test, performed during a 4 h dwell with a 2.27% glucose solution, evaluates low molecular weight solute transfer [using the dialysate/plasma (D/P) ratio of creatinine at the end of the procedure and the ratio of dialysate glucose concentration at 240 min/dialysate glucose concentration at initiation of the test (D/D0)], as well as net UF. Recently, an International Society for Peritoneal Dialysis committee on UF failure proposed performing the PET with a 3.86%-based solution instead of the 2.27% glucose PET [3]. As compared with classical PET, hypertonic PET provides similar information on small solute transport but is more sensitive in detecting clinical UF failure and gives better data on free water transport through aquaporins [4,5]. Currently, the patient-related determinants of the transport characteristics of small solutes, proteins and water through the PM, as well as their evolution during PD therapy, are still a matter of debate.

In the present study, we first document, using a 3.86% PET in a cohort of consecutive patients, that the characteristics of the PM transport properties at onset of PD are influenced by clinical factors and, second, that they might change with time on PD.



   Subjects and methods
Top
 Abstract
 Introduction
 Subjects and methods
Results
 Discussion
 References
 
Evaluation of PM transport properties and of their determinants at onset of PD (baseline PET)
Patients
Between 1 March 1997 and 28 February 2003, 78 patients were started on PD at Cliniques Universitaires St-Luc, Belgium. All of them were dialysed through a pigtail swan-neck Missouri coiled catheter surgically inserted 1–3 weeks before dialysis onset. All patients were initially started on continuous ambulatory peritoneal dialysis (CAPD) using three 1.5–2.5 l (according to patient's size) glucose-based dialysates (Baxter Healthcare, Round Lake, IL, USA) and an icodextrin-based dialysate (Baxter Healthcare) overnight.

Of these 78 patients, 72 patients underwent the baseline PET (see below) within 4–6 weeks after PD onset. Six patients were not enrolled because of early death (n = 2), kidney transplantation (n = 2) or peritonitis (n = 1) before PET determination or incomplete data (n = 1). The charts of these 72 patients were reviewed to assess the prevalence of various clinical characteristics, such as age, gender, body surface area (BSA), type of nephropathy, prevalence of diabetes, residual renal function (RRF), drug prescription – chosen for their potential influence on endothelium [angiotensin-converting enzyme (ACE) inhibitors and statins] and on water transport (steroids) [6] – and biological values (see below).

Peritoneal permeability analysis
Permeability analysis was performed using a PET, as described by Twardowski et al. [2] with the difference that the test bag was a 3.86% glucose-based dialysate (instead of a 2.27% glucose-based dialysate in the original description).

Before instillation of the test solution, the peritoneal cavity was rinsed with 2 l of 1.36% glucose dialysate and immediately drained after inflow completion. A 1.5 or 2 l 3.86% test bag was then infused. Ten millilitres dialysate samples were collected from the test bag before inflow and 0, 30, 60, 120 and 240 min after its intraperitoneal instillation and blood samples were drawn after 120 min of dwell time, as described previously [2]. Five aliquots of serum and dialysate samples of each PET were also frozen immediately at –80°C. Net UF, i.e. the net difference between dialysate volume effluent and volume infused, was recorded. Measurements of serum urea, creatinine, glucose, sodium, cholesterol and phosphate were performed using routine laboratory techniques on an LX 20 analyser (Beckman-Coulter, Fullerton, CA, USA). The Jaffé method was used for creatinine determinations and the results were corrected for the interference with high glucose levels. Albumin in both serum and dialysate was measured by immunonephelometry on the BN II analyser (Dade Behring Inc., Deerfield, IL, USA).

Frozen serum and dialysate samples were later defrosted, centrifuged and vortexed to perform the analysis of ultrasensitive C-reactive protein (CRP), {alpha}2-macroglobulin and ß2-microglobulin. {alpha}2-Macroglobulin and serum ultrasensitive CRP were measured by immunonephelometry on the BN II analyser (Dade Behring Inc.). Serum ß2-microglobulin was measured by IMMUNOTECH ß2-microglobulin radioimmunoassay kit (Beckman-Coulter).

BSA was calculated as follows:

Formula
(weight is expressed in kg and height in cm).

The mass transfer area coefficient (MTAC) of creatinine, phosphate and glucose was calculated according to Waniewski et al. [7]. Sodium sieving ({Delta}D/P sodium) was defined as the ratio of the difference between sodium concentrate dialysate at the beginning of the PET and at 1 h, on serum sodium [5,6], with a correction for sodium diffusion using MTAC creatinine. The dialysate clearances of the different proteins (albumin, ß2-microglobulin and {alpha}2-macroglobulin) were calculated using the following formula:

Formula
where [solute] represents the solute concentration.

RRF was evaluated using creatinine clearance determined by the UV/P formula:

Formula

Longitudinal evolution of PM transport properties
Patients
After the results of baseline PET were available, all patients were offered to continue on CAPD or to be trained on automated PD (APD) (Home Choice Pro; Baxter Healthcare), independently of the PET results. Among the 72 patients in whom the initial PET was performed, 35 were followed-up at 12 months and were thus eligible for the longitudinal study. For all, we checked PD characteristics (APD or CAPD, use of icodextrin) and peritonitis rate. The second PET (PET at 1 year) was not performed in the remaining 37 patients because of renal transplantation within the first year of PD (n = 13), definitive transfer to haemodialysis (HD) (n = 8), patient still on PD for <1 year at follow-up (n = 8), death (n = 4), temporary transfer to HD at the time of one of the PET (n = 3) and subjective intolerance of 3.86% glucose-based dialysate (n = 1). To rule out a potential influence of clinical parameters and of the baseline PM transport characteristics on outcome, the data of the 35 included were compared with those of the 37 non-included patients. Few statistical differences in clinical and biological parameters or in PM transport properties’ markers were detected between both groups, except for the serum albumin concentration (3.85±0.52 vs 3.52±0.64 g/dl; P = 0.03) and the clearance of albumin, which were moderately higher in the included patients (Table 1). As both groups are similar for clinical factors and comparable for PM transport properties, conclusions regarding the longitudinal evolution of the PM can be drawn from the 35 included patients that may, thus, be considered as representative of the whole population.


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  		Table 1. Baseline characteristics of all patients and comparison between included and non-included patients for the longitudinal part of the study

 
PET at 2 years of PD was available in 18 of the 35 patients; 17 patients were not evaluated for the following reasons: renal transplantation (n = 8), patient still on PD but for <2 years (n = 4), definitive transfer to HD (n = 3) or death (n = 2). The reasons of transfer to HD were persisting peritonitis (n = 1), pleuro-peritoneal communication (n = 1) and personal choice (n = 1). One patient died from myeloma and one from fecal peritonitis. Except for PD duration (37.7±9.4 vs 19.5±3.6 months; P<0.001), there was no statistical difference between the 18 patients evaluated at 2 years and the 17 patients lost to follow-up between the first and second year of PD, as far as the following parameters were considered: age, gender, BSA, sodium sieving, net UF, presence of diabetes or glomerulopathy, incidence of peritonitis, prescription of steroids, ACE inhibitors or statins, MTAC creatinine, sodium sieving and clearance of {alpha}2-macroglobulin.

Study design and statistical analysis
This is a single-centre longitudinal study of clinical and biological data collected prospectively. All patients starting PD during the study period were enrolled. Discrete data are reported as percentages and continuous data are reported either as means±SD if normally distributed or as geometric mean with geometric SD if normally distributed on log scale (lognormal). Statistical tests were performed on log-transformed data for all variables presenting with a lognormal distribution. All clinical and functional data collected at baseline were compared between patients with a follow-up time >12 months (n = 35) and patients lost to follow-up before 12 months (n = 37) using a Fischer exact P-value for counts and a Student's t-test for continuous variables. Correlations between clinical or biological factors and indices reflecting the PM transport properties were assessed using the Pearson's cross-product coefficient (r). Significantly correlated factors were submitted to a multiple linear regression with a forward stepwise selection procedure to find out factors independently correlated with indices of the PM transport characteristics. Changes over time in indices of the PM transport properties were tested for linear trends using analysis of variance (ANOVA) for repeated measurements with F-tests and contrasts were performed using paired t-tests. The statistical significance level was set to 0.05. All analyses were performed with the SPSS 11.0 statistical software.

Ethical considerations
The PET was part of the normal procedure of care for PD patients. All patients gave oral informed consent for the storage of blood and dialysate samplings. The study design was approved by the local ethical committee.



   Results
Top
 Abstract
 Introduction
 Subjects and methods
 Results
Discussion
 References
 
Evaluation of PM transport characteristics and of their determinants of the initial PET
The reference values for PM transport characteristics, as determined with a hypertonic PET for the 72 patients who performed baseline PET, are presented in Table 1. Mean age of the patients was 51±19 years and there was a preponderance of males (64%). Fourteen (19%) and 20 (28%) patients were given steroids and statins, respectively; 29 patients (40%) were given ACE inhibitors either for ischaemic heart disease (n = 7) or hypertension (n = 22).

D/P creatinine ratio at the fourth hour in our population averaged 0.74, giving a mean (±SD) MTAC creatinine of 8.14±1.6 ml/min; after correction for BSA, it corresponded to 4.71±1.6 ml/min/m2. Sodium sieving corrected for sodium diffusion was 0.059±0.022.

Several clinical factors did affect initial MTAC creatinine using univariate analysis (Table 2): BSA (r = 0.26, P = 0.03), presence of diabetes (r = 0.26, P = 0.03) and intake of ACE inhibitors (r = 0.31, P = 0.01) were positively correlated, while serum albumin (r = –0.46, P<0.001) and net UF (r = –0.33, P = 0.009) were inversely correlated with MTAC creatinine. No correlation could be found between RRF and MTAC creatinine. Similar correlations were obtained when MTAC creatinine was normalized for BSA (data not shown). On multivariate analysis using a stepwise selection procedure, the independent covariates that affect MTAC creatinine were (step 1) serum albumin (R2 = 0.208, P<0.001) and BSA (R2 = 0.289, P = 0.01) and (step 2) ACE inhibitor prescription (R2 = 0.158, P = 0.01).


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  		Table 2. Determinants of the MTAC creatinine and sodium sieving at onset of PD by univariate analysis

 
MTAC creatinine in patients given or not an ACE inhibitor averaged 9.77±1.66 vs 7.24±1.55 ml/min (P = 0.012), respectively. The effect of ACE inhibitor prescription on MTAC creatinine was independent of its indication of prescription (ischaemic heart disease or hypertension; F = 0.7; P = 0.39 by two-way ANOVA with interaction analysis). As compared with patients not given ACE inhibitors, patients given ACE inhibitors also had a higher incidence of diabetes (7% vs 24%; P = 0.04) and a lower serum albumin concentration (3.49±0.58 vs 3.81±0.59 g/dl; P = 0.03).

The clinical factors that affect sodium sieving at onset of PD are presented in Table 2. Only BSA was inversely correlated with initial sodium sieving on both univariate (r = –0.33, P = 0.01) and multivariate analysis (R2 = 0.108, P = 0.011). There was no significant correlation between steroid prescription and sodium sieving.

There was a strong correlation between MTAC creatinine and sodium sieving (r = –0.41, P<0.01) (Table 2).

The clinical factors that affect the clearances of albumin, ß2-microglobulin and {alpha}2-macroglobulin are presented in Table 3. Serum albumin inversely correlated with albumin clearance in univariate analysis (r = –0.39, P = 0.02). We observed a trend (P<0.10) for age, BSA and diabetes to positively correlate and for female gender to negatively correlate with albumin clearance. Age, but not BSA, also correlated positively with the clearances of ß2-microglobulin and {alpha}2-macroglobulin. A positive correlation was also observed between diabetes and RRF, and {alpha}2-macroglobulin. On multivariate analysis, the independent covariates that affected {alpha}2-macroglobulin were age (P = 0.03), diabetes (P = 0.01) and RRF (P<0.01).


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  		Table 3. Determinants of the clearances of proteins at onset of PD by univariate analysis

 
Longitudinal evolution of PM transport characteristics
The evolution of the PM transport characteristics in the 35 patients with >1 year of PD is presented in Table 4. Serum albumin significantly decreased over time (3.9 g/dl at baseline PET vs 3.6 g/dl at PET after 1 year; P = 0.02), as did serum cholesterol (P = 0.05). This latter observation has to be viewed with caution as the number of patients receiving statins increased from seven at baseline PET to 15 at PET after 1 year. MTAC creatinine remained virtually unchanged.


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  		Table 4. Evolution of the peritoneal permeability markers during the first year of PD

 
The evolution of the PM transport characteristics of the 18 patients evaluated at PET after 2 years is presented in Table 5. MTAC creatinine (P = 0.026) slightly increased with time. A trend to a progressive loss of UF was also observed (P = 0.08). Sodium sieving did not change with time. The decrease in serum albumin seen after 1 year of PD was even more accentuated. In contrast, no significant modifications were observed for albumin, ß2-microglobulin and {alpha}2-macroglobulin clearances. Finally, the significant increase in BSA with time was confirmed.


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  		Table 5. Evolution of the peritoneal permeability markers during the first 2 years

 
Correlation analysis between various PM transport characteristics, including 35 patients for baseline PET and 18 patients for PET after 1 and 2 years, respectively, were performed. A strong correlation was observed between MTAC creatinine and UF at each time point. Strong correlations were also detected for the differences observed between baseline PET and PET at 1 year for (i) MTAC creatinine and sodium sieving (r = –0.48, P = 0.002; Figure 1), (ii) between MTAC creatinine/BSA and sodium sieving (r = –0.52, P<0.001; data not shown) and (iii) between MTAC creatinine and albumin clearance (r = –0.36, P = 0.04; Figure 2). Similar observations were made for patients between baseline PET and PET at 2 years (data not shown). {alpha}2-Macroglobulin clearance was also strongly correlated with albumin clearance (P<0.001 at each time point).


Figure 1
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  		Fig. 1. Relation between sodium sieving increase and MTAC creatinine (log) increase after 1 year of PD, illustrated by linear regression. There was a strong correlation between MTAC creatinine and sodium sieving variation (P = 0.002): a gain in MTAC creatinine induces a reduction of sodium sieving.

 

Figure 2
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  		Fig. 2. Relation between serum albumin concentration variation and MTAC creatinine (log) increase after 1 year of PD, illustrated by linear regression. There was a good correlation between MTAC creatinine and albumin variation (P = 0.04): an increase in MTAC creatinine is associated with a decrease in serum albumin concentration.

 
Finally, we analysed the impact of clinical factors, such as PD modality (CAPD vs APD), peritonitis incidence (0 or ≥1), diabetic status, BSA, age, sex, the presence of a chronic glomerulonephritis as the cause of end-stage renal disease, the prescriptions of steroids, ACE inhibitors or statins, and ultrasensitive CRP on the variation of MTAC creatinine, sodium sieving, UF and {alpha}2-macroglobulin clearance. No statistically significant influence of any of these clinical or biological parameters on the evolution of the peritoneal transport markers was detected. Especially, neither the PD modality nor the occurrence of peritonitis influenced the evolution of these various markers.



   Discussion
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
References
 
We here document that the PM transport characteristics for small solutes at onset of PD, as evaluated by a 3.86% glucose-based PET in a series of consecutive PD patients, may be influenced by clinical factors, such as BSA, presence of diabetes and prescription of ACE inhibitors. We also show that sodium sieving is linked to BSA and that clearance of a high molecular weight protein, such as {alpha}2-macroglobulin, may be affected by age, diabetes and RRF. In addition, we document that the transport of low molecular weight solutes may change with time on PD, while 71% and 94% of the patients were on APD and were given icodextrin during long dwells, respectively.

Determinants of PM transport characteristics at onset of PD
The PM transport characteristics at PD onset evaluated here in 72 patients are comparable with those obtained in previous studies using either a 3.86% PET [8,9] or, even, a 1.36% PET [10], as the convective transport of small solutes can be considered as negligible.

We document that some clinical factors did affect the baseline peritoneal solute transport rates. Solute transport tended to be higher in diabetic patients, in patients given an ACE inhibitor and in patients with a low serum albumin concentration. This probably reflects that the higher the patient comorbidity, the higher the transport rates, as already suggested by some [11–15], but not all, authors [16]. Our observation supports the hypothesis that systemic inflammation associated with comorbid diseases, hypoalbuminaemia and elevated interleukin (IL)-6 level as surrogate markers may result in peritoneal vascular changes, such as vasodilation and neoangiogenesis and, thus, in changes in the PM properties due to the subsequent increase in peritoneal blood flow [13]. In this context, the recent finding of Gillerot et al. [15] that a peculiar polymorphism of the IL-6 gene is associated with high-transport status and elevated serum and dialysate IL-6 concentrations is of interest. The absence of relation between age (as shown by Davies [14] and in the Australasian study, Rumpsfeld [16], where the risk of being a high transporter was increased by 8% for every decade of life) or CRP level and transport rates in the present study probably does not preclude this hypothesis of ‘peritoneal inflammation’, given our small number of included patients. The association between low albumin and an increased transport rate observed here as well as in previous studies [11–15] has, however, to be interpreted with caution, as hypoalbuminaemia could be either a witness of fluid overload in high transporters (rather than a marker of systemic inflammation) or the result of increased albumin losses in patients with high solute transport. The inverse correlation between serum albumin and albumin clearance observed in our patients at the onset of PD further illustrates the difficulty of this matter.

The effect of ACE inhibitor merits more attention, as ACE inhibitor prescription did affect small solute transport rates independently of the indication of prescription. As already mentioned, this observation could reflect comorbidity (in favour of this hypothesis is the fact that patients given ACE inhibitors also had a higher incidence of diabetes and a lower serum albumin concentration) or, alternatively, it could be accounted for by a direct effect of ACE inhibitors on the peritoneum, as discussed recently by Duman [17].

Contrary to the findings of Davies, a correlation between gender or RRF and creatinine transport rates [14] was not found in the current study. However, in the Davies' study, the gender effect could be explained by a difference in BSA and the absence of effect of RRF in our study is probably related to our small number of patients.

In contrast, we document a positive correlation between BSA and MTAC creatinine and, also, a negative correlation between BSA and sodium sieving. It is, thus, tempting to speculate that the higher the BSA, the higher the effective peritoneal surface area: more small pores available for transport lead to a higher glucose absorption from the peritoneal cavity to the blood. As a consequence, aquaporin-mediated water transport decreases, leading to a lower sodium sieving and a reduced net UF: the relationship BSA–sodium sieving is, thus, more a secondary rather than a ‘cause-and-effect’ association. This latter point further confirms the well-known relationship between UF and MTAC creatinine that is, at least at PD onset, not yet influenced by increased fluid lymphatic reabsorption and aquaporin dysfunction.

Altogether we have to acknowledge that all these above-mentioned determinants interact with each other and this may explain why age or gender for instance predominates in one study and body mass index in another. In this context, it is of interest to note that a recent work of Selgas and co-workers [18] did not document a relationship between solute transport and age, gender, diabetic status or patient size in a large cohort of Spanish patients, indicating that much work has to be done to explain the variability in solute transport in patients commencing PD.

No correlation between sodium sieving and steroid prescription could be found in the present study. An over-expression of aquaporin by steroids in humans, as it has recently been documented in a rat model [6]. Thus, could not be documented here. It would be of considerable interest to test this hypothesis in a larger population of PD patients given steroids for any reason.

The analysis of the determinants of the clearances of proteins of various molecular size and weight (ß2-microglobulin: 16 Å, 11.8 kDa; albumin: 36 Å, 66 kDa; and {alpha}2-macroglobulin: 89 Å, 718 kDa) is also of interest. ß2-Microglobulin clearance was positively correlated with age in univariate analysis while a trend, though not statistically significant, for age, gender, BSA and diabetes (P<0.10 for each in univariate analysis) to affect albumin clearance was noticed. In contrast, the clearance of {alpha}2-macroglobulin was affected, in both uni- and multivariate analyses, by age, diabetes and RRF. Some potential variations in the size of the large pore population, with subsequent increased leakiness, may thus occur secondary to age and diabetes. Interestingly, Heaf and co-workers [19] recently documented a correlation between large pore fluid fluxes, as evaluated by the PDC program, and age (but not with diabetes) and subsequent hypoalbuminaemia and increased mortality.

Longitudinal evolution of PM transport characteristics
The next step in our study was to determine the longitudinal evolution of the PM transport characteristics over the first 2 years of PD. Interestingly, small solute transport (MTAC creatinine) increased over time, as was observed a trend to a decrease in net UF (Table 4). This finding, not unusual in very long-term PD patients [20,21] was more unexpected in our patients as they were on PD for a maximum of 2 years. This rise in transport rates occurred despite the absence of influence of either individual characteristics (gender, age, type of nephropathy and presence of a diabetes), concomitant therapies (ACE inhibitors and statins), incidence of peritonitis or mode of PD (APD vs CAPD) therapy. A correlation between the evolution of the RRF and the fate of the PM transport characteristics, unfortunately not analysed here because of lacking data, would have been of interest. Interestingly, Davies [14] also recently documented that, when confined to patients with a change in D/P creatinine ratio >0.1 within the first year of PD, this was three times more likely to be an increase. Altogether, an increase in small solute transport rate is the consequence of an increase in effective vascular surface area, as reflected by the increased vascular density (and therefore in blood flow), observed in the peritoneum of PD patients [22]. Yet the present study includes a small number of patients followed over a short period of time; this limits its statistical power and the putative influence of other clinical parameters. This limitation might also explain the lack of beneficial effect of ACE inhibitors and of icodextrin (as it has been documented recently in the EAPOS study [23]) on the evolution of PM transport characteristics. Finally, no modification in the transport rates for larger molecules, such as ß2-microglobulin and {alpha}2-macroglobulin, could be detected. Taken together, this points to membrane changes with time that are due to increased blood flow rather than increase in pore-size permeability, at least during the first 2 years of PD therapy.

We also observe a correlation between modifications in MTAC creatinine and sodium sieving (P = 0.002; Figure 1). Not unexpectedly, a rise in MTAC creatinine (and also, in parallel in MTAC glucose, with a reduction of the osmotic gradient as a consequence) induces a reduction in sodium sieving. The rationale for aquaporin investigation was based on some previous findings that the aquaporin function could be damaged by the PD procedure [5]. Our data indicate a conservation of the aquaporin patency, at least during the first 2 years of PD. Though the determination of aquaporin function is usually assessed by the determination of sodium sieving, we think that more sophisticated (clinical or computerized) tools should be used in the future to test free-water transport alterations in long-term PD patients in order to avoid the ‘coupling’ effect between small solute transport and water transport.

In concordance with previous longitudinal studies [20], we finally observed a significant decrease in serum albumin concentration with time on PD that was correlated with a rise in MTAC creatinine: the higher the increase in MTAC creatinine, the lower the serum albumin concentration. This finding could be evidence of either a progressive malnutrition or of a clinically undetected fluid retention rather than an increased albumin loss across the PM, as peritoneal albumin clearance had remained virtually unchanged (Tables 4 and 5).

In conclusion, our observations suggest that clinical conditions, probably in association with genetic variants [15,16], may affect the PM transport properties at baseline. This information has to be taken into consideration by clinicians, as patients with a high transport status are likely to require more hypertonic dialysates, a condition considered to be deleterious for the PM [21]. It is also of note that, in comparison with the data obtained at onset of PD, the PM characteristics are modified, even after a short-term (2 years) exposure to PD, as a trend to a significant increase in small solute transport properties is observed. It is, nevertheless, difficult to identify the different risk factors responsible for changing the PM transport characteristics. The consequences of these changes are, however, not anecdotal: patients with a rise in small solute transport rates exhibit a fall in serum albumin concentration and are therefore at increased risk for further complications [12]. Altogether, the findings from the present study do not detract from the marked improvements achieved in PD recent years: the mortality of PD patients continuously decreases and the use of new, more biocompatible dialysates is promising to increase technical survival.



   Acknowledgments
 
This study could not have been done without the help of the nurses of the PD unit, of Y. Cnops for collection of serum and dialysate samples and of B. Janssens de Varebeke for data management. We also thank Prof. M. Jadoul, Y. Pirson and O. Devuyst for their critical comments and advice and Prof. Ph. de Naeyer and M. Philippe for their contributions. Presented in part, orally, at the XLI congress of the ERA–EDTA, Lisbon, 2004, and in poster forms at the first Joint Meeting ISPD/Euro PD Congress on Peritoneal Dialysis, Amsterdam, 2004, and at the Renal Week of the ASN, St Louis, MO, USA, 2004.

Conflict of interest statement. None declared.



   References
Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. Gokal R. Taking peritoneal dialysis beyond the year 2000. Perit Dial Int 1999; 19: S35–S42[Abstract/Free Full Text]
  2. Twardowski ZJ, Nolph KD, Khanna R et al. Peritoneal equilibration test. Perit Dial Bull 1987; 7: 138–147
  3. ISPD ad hoc committee on ultrafiltration management in peritoneal dialysis. Perit Dial Int 2000; 20 [Suppl 4]: S3–S4
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Received for publication: 27. 3.05
Accepted in revised form: 23.11.05


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