The Personal Dialysis Capacity Test Is Superior to the Peritoneal Equilibration Test to Discriminate Inflammation as the Cause of Fast Transport Status in Peritoneal Dialysis Patients

Materials and Methods

All new (incident) patients who started PD at the University Hospital Ghent between January 1, 1998, and December 31, 2003, were included in this prospective observational study. In all patients, a standard PDC test was performed during the first 3 mo of their PD treatment. The PDC test was performed as described earlier (15). In brief, patients were visited at home and given the instructions for the PDC regimen (five exchanges) and the collection of the dialysate samples and 24-h urine. A blood sample was drawn. The five exchanges all alternated in glucose concentration and duration (one of 3 h, one of 4 h, one of 5 h, one of 2 h, and one of 10 h) to maximize the effectiveness of the mathematical model. All solutions were low in glucose degradation products at neutral pH. For the 4-h dwell, always a 2.27% glucose solution was used, which allowed calculation of D/P values at 4 h, the key parameter of the PET. The preceding exchange was always 1.36% glucose to avoid carryover effect differences (20,21). The glucose concentrations for the remaining exchanges were at the discretion of the physician in function of the volume status of the patient. Patients noted for each exchange the exact time of start of the drainage, the total drained volume, and the time of start of the inflow on the specifically designed PDC test sheet. The next day, patients brought the collected samples of PD fluid and urine to the hospital, and a second blood sample was drawn. Patients who were on APD were converted to continuous ambulatory peritoneal dialysis (CAPD) for the duration of the PDC test. Data were entered in the PDC program (Gambro, Lund, Sweden), and the PDC-derived parameters were calculated.

Demographic data and biochemical parameters were measured. Inflammation was assessed by the determination of serum C-reactive protein (CRP) levels, using the latex-enhanced immunoturbidimetric method (Tina quant; Roche Diagnostics, Switzerland) on a Modular P analyzer (Hitachi, Tokyo, Japan). Patients with a serum CRP level >10 mg/L were considered to have inflammation.

Residual renal function was determined by collection of a 24-h urine sample, as is usual during the PDC test. Both urea and creatinine clearance were calculated, and GFR was determined as the mean of urea and creatinine clearance. Serum albumin was determined by nephelometry.

Ultrafiltration was defined as the total ultrafiltration obtained during the PDC test day by the PDC test day regimen. Thus, it does not reflect the actual ultrafiltration of the patient on his or her day-to-day CAPD regimen but rather the ultrafiltration capacity in response to a standardized regimen.

Comorbid conditions were noted at baseline (i.e., the moment of PDC test). Diabetes was defined as need for oral antidiabetics or insulin, actual or in the past.

Results

In total, 135 patients were included in the study. No patient refused to perform the test, and acceptance of the PDC test in this study was good.

Inflammation, Membrane Characteristics, and Outcome

In the univariate analysis, inflammation (relative risk [RR] 1.8 per mg/L CRP; P = 0.007), serum albumin (RR 0.92 per g/dl; P = 0.06), diabetes (RR 2.2; P = 0.02), and age (RR 1.07/yr; P < 0.001) were predictive for worse outcome but not A0/dX, or J_vL, or D/Pcrea at 4 h (Table 6). In a multivariate Cox regression analysis with correction for age, diabetes, CRP, and serum albumin, patients who had a J_vL higher than expected by their A0/dX had a higher mortality than those who had a normal J_vL according to their A0/dX (Figure 1). D/Pcrea at 4 h was not related to mortality in any of the multivariate analyses.

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Figure 1.

Survival of patients with or without increased larger pore flux (J_vL; corrected for age, diabetes, C-reactive protein and serum albumin, and potential interaction terms). Patients are divided into those with a J_vL higher than expected by their surface area over diffusion distance (A0/dX; “increased,” solid line) and those with a normal J_vL as related to their A0/dX (normal, dotted line). P = 0.04.

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Table 6.

Cox regression analysis for mortality: Univariate analysis

Discussion

The relation between inflammation and high transport status is probably the most important explanation for the increased mortality risk found in PD patients with an FTS. This analysis demonstrates that the use of D/Pcrea based on the PET leads to an incorrect perception of the mortality risk of PD patients with FTS, as with PET-based information alone, the different causes of FTS cannot be discriminated. In contrast, with the PDC test, the combined interpretation of the J_vL and the unrestricted area for diffusion corrected for diffusion distance (A0/dX) allows much better discrimination of inflammation from anatomic constitution as a cause of an FTS. When age is taken into account, a higher-than-expected J_vL by A0/dX and CRP level are equipotent predictors of outcome, whereas D/Pcrea is not. Analysis of the peritoneal membrane characteristics with PDC test thus is more informative than a simple PET. This discrimination has important prognostic and therapeutic consequences, because for patients with a large surface area but without inflammation, outcome can be improved by increasing the fill volume or by the use of icodextrin, whereas for patients with inflammation, the underlying cause of the inflammation should be identified and eventually cured. If no evident cause of the inflammation is found, then use of more biocompatible PD solutions (22,23) or a transfer to hemodialysis to rest the peritoneal membrane should be considered. In patients with inflammation, use of icodextrin and of short cycles is also warranted to avoid overhydration, which might be an important additional cause of the inflammation and the increased mortality in these patients (5,6,9,24,25).

The PET (26) is the most widespread tool used to analyze peritoneal membrane characteristics (18). The test, however, has several drawbacks (27,28). First, the categorization into four groups has only limited value, as it has been validated only in a (limited) North American population. For other populations, epidemiologic adaptations should be made, especially when patient physiognomy is strongly different from the “average” American patient, e.g., in Asian patients (29–31). Using the D/Pcrea ratio at 4 h gives already a more objective and continuous representation of the transport status of the membrane. For CAPD patients, this in addition gives the advantage that peritoneal clearances can easily be estimated (32), although still then, caution must be taken to extrapolate PET data to clearances in individual patients (28), whereas PDC allows calculation of the effect on clearance and ultrafiltration of different alternative regimens. Second, the use of a standard instillation volume in the PET leads to bias. In PDC, the fill volume of the different dwells can be adapted to the clinical needs of the patient. In addition, in a slow transporter, the D/Pcrea is further falsely decreased by the dilution created by the additional convective flow. Third, newer evaluation methods of the peritoneal membrane, such as PDC or Peritoneal Function Test (Fresenius Medical Care, Bad Homburg, Germany) can be performed by the patient at home, even for the blood sample, which can be drawn when the patient collects his or her material or during a home visit. For the PET, although always advocated as a more simple and more patient-friendly method, the patients have to come to the clinic and stay for at least 4 h. In our institution, where PDC is performed routinely, no patient has ever objected to this procedure, and most prefer it over staying 4 h in the outpatient clinic to perform a PET.

Our study highlights another important advantage of PDC over PET: It gives more essential information on the peritoneal membrane characteristics. With a PET, it is impossible to discriminate inflammation, which leads to changes in membrane quality and vascular recruitment and thus an increased area for diffusion on the one hand and anatomic large surface area with normal distribution of the vessels on the other hand by a PET. In this study, we found a substantial misclassification of “inflammation” when only D/P was taken into account. In contrast, by using a composite marker of PDC data, i.e., J_vL that is higher than expected on the basis of the A0/dX, we were able to discriminate inflammation from other causes of FTS. This finding also suggests that during inflammation, not only recruitment of vessels takes place but also a change in pore and membrane quality, as large pore flow increases more rapidly than the perfused area. It gives an explanation for the observed differences in transport of water and large solutes and small uremic toxins: In inflammation, there is not only vascular recruitment but also alterations in membrane porosity.

Serial measurement of the PDC data also allows timely detection of changes in peritoneal membrane characteristics (17). An increase in J_vL without a correlated increase in A0/dX might be a warning sign that the peritoneal membrane is wearing off and that a (temporary?) transfer to hemodialysis might be indicated.

Another important finding in this study is the independent impact of J_vL, when corrected for A0/dX, on mortality. An in-depth analysis of the PDC-derived parameters thus yields a powerful prognostic marker.

In a previous study, Johnson et al. (14) demonstrated that the PDC-derived A0/dX was superior to PET-derived D/Pcrea at 4 h in describing the transperitoneal membrane transport of small solutes. This study adds another argument in favor of the PDC test as compared with the PET: A better discrimination of inflammation versus anatomic constitution as the cause of an FTS. In view of the prognostic difference between these two conditions, this is a relevant finding.

Conclusion

This article demonstrates that PDC delivers more information on peritoneal membrane status than a classic PET. This information has both prognostic and therapeutic importance. J_vL, when corrected for A0/dX is a marker of inflammation and is related to outcome.