Baxter-Travenol, Deerfield, Illinois, U.S.A.) with an intraperitoneal volume marker (1311-human albumin,. RISA) and frequent blood and dialysate sampling. The.
Proceedings of the ISPD '98 -The VIIIth Congress of the ISPD August 23 26, 1998, Seoul, Korea Peritoneal Dialysis International, Vol.19 (1999), Supplement 2
0896-8608/99 $300 + .00 Copyright © 1999 International Society for Peritoneal Dialysis Printe d in Canada All rights reserved
A SIMPLE AND FAST METHOD TO ESTIMATE PERITONEAL MEMBRANE TRANSPORT CHARACTERISTICS USING DIALYSATE SODIUM CONCENTRATION
Tao Wang, 1 Jacek Waniewski, 1,2 Olof Heimbürger,1 Jonas Bergstrβm,1 Andrzej Werynski,2 and Bengt Lindholm1 Divisions of Baxter Novum and Renal Medicine, 1 Department of Clinical Sciences, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden; and Institute of Biocybernetics and Biomedical Engineering,2 Warsaw, Poland
KEY WORDS: Peritoneal equilibration test; sodium; peritoneal transport. Correspondence to: B. Lindholm, Divisions of Baxter Novum and Renal Medicine K-56, Huddinge University Hospital, Karolinska Institute, S-14186 Huddinge, Sweden.
peritoneal equilibration test (PET) is a widely used T hemethod to classify patients' peritoneal trans port characteristics (1-3). It has been convincingly shown that PET guides the formulation of an appro priate dialysis prescription for continuous ambulatory peritoneal dialysis (CAPD) patients (2,4-7). Also, peritoneal transport characteristics based on PET have recently been shown to have a major impact on clinical outcome (8-11). Because peritoneal transport characteristics change with time on dialysis, repeated equilibration tests are required to optimize the peritoneal dialysis prescription for chronic dialysis patients (12,13). However, the standard PET has several drawbacks: (1) It is laborious, requires approximately 5 h to complete, and consumes nursing time to administer the test (14). (2) Blood sampling is needed, and the patient has to come to the hospital to be tested. (3) The method for measurement of creatinine is affected by dialysate glucose in most clinical laboratories, and therefore various correction factors must be set up to correct for the influence of glucose on the creatinine measurement (1). (4) The prediction ofPET to peritoneal fluid removal is generally poor (7). Recent studies suggest that adequacy of peritoneal dialysis is a matter not only of reaching targets for small-solute clearances, but also -and maybe even more important -of removing enough fluid and sodium (10,15). Therefore, it is important to find parameters that can be used to predict both the peritoneal membrane diffusive permeability and peritoneal fluid removal. It is well known that peritoneal sodium transport is strongly dependent on peritoneal fluid removal (16,17). In recent years, the decrease in dialysate sodium concentration (owing to substantial sieving of sodium) during the initial part of a peritoneal dialysis dwell using hypertonic 3.86% glucose solution has been suggested as a measure of trans cellular water transport (18-21). In addition, DIP sodium at 60 min of the dwell has been proposed to be used as a marker
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.Background:The peritoneal equilibration test (PET) is widely used to classify a patient's peritoneal transport characteristics. However, PET is laborious and the prediction of fluid removal based on PET is generally poor. It is believed that osmosis by glucose occurs partially through transcellular water channels, resulting in sieving of sodium and decrease of dialysate sodium concentration when using hypertonic glucose dialysate. .Objective: In this study, we investigated the possibility of using dialysate sodium concentration to classify the patient's peritoneal transport characteristics. .Methods: A 6-hour dwell study with frequent dialysate and plasma sampling was performed in 46 patients using 2 L of 3.86% glucose dialysate with 1311-albumin as an intraperitoneal volume (IPV) marker. The peritoneal transport of sodium, creatinine, glucose, and fluid was evaluated. .Results:The dialysate sodium concentration at 240 min (ONa240) significantly correlated with O/P creatinine (r = 0.76, p < 0.001) and O/O0 glucose (r = -0.83, p < 0.001) at 240 min of the dwell (better than dialysate sodium concentration at any other time of the dwell). ONa240 also significantly correlated with IPV at 240 min of the dwell (r = -0.61, p < 0.001) (better than O/P creatinine and O/O0 glucose). There were significant correlations between ONa240 and the sodium-sieving coefficient (r= 0.71, p < 0.001) and the diffusive mass transfer coefficient for sodium (r = 0.50, p < 0.001 ). When using ONa240 to divide the patients into four groups, as in the PET method, no significant difference was found between the two methods. .Conclusion: Using 3.86% glucose solution, ONa240 can be used instead of O/P creatinine to classify patients into different transport groups. ONa240 provides a better prediction of peritoneal fluid transport and reflects both the diffusive and convective transport properties of the membrane. As only one dialysate sample (and no blood sample) is needed, ONa240 may offer important clinical advantages compared with PET.
METHODS In this analysis, we used data from 46 6-hour dwell studies using 2 L of 3.86% glucose dialysis fluid (Dianeal, Baxter-Travenol, Deerfield, Illinois, U.S.A.) with an intraperitoneal volume marker (1311-human albumin, RISA) and frequent blood and dialysate sampling. The study protocol has been described in detail previously (22). The dwell studies were performed as part of a long-term follow-up of CAPD patients or as part of studies on alternative osmotic agents, and some of the dwell studies reported here have been partly analyzed before (17,22,23). Blood and dialysate samples were analyzed for RISA activity on an Intertechnique CG Gamma Counter (lntertechnique, Plaisir, France). Glucose and creatinine concentrations were measured with an IL 919 system (lnstrumentation Laboratory, Milan, Italy), and sodium concentration, with an IL 743 flame photometer (lnstrumentation Laboratory, Milan, Italy). Intraperitoneal dialysate volumes (V J were estimated from the dilution of RISA with corrections applied for the elimination rate of RISA from peritoneal cavity (KE, mL/min) and sample volumes. KE was used for estimating the peritoneal fluid absorption rate (24). The dialysate concentration (CD) over plasma concentration (CE) ratio, DIP, during the dwell study was calculated by dividing the dialysate concentration of a solute with the plasma water concentration of the investigated solute (25). The diffusive mass transport coefficient, KED (mL/min), and the sieving coefficient, S, were calculated using the modified BabbRanderson-Farrell model as described previously (26) using the computer program PERTRAN (Baxter Novum, Karolinska Institute, Stockholm, Sweden).
We classified the patients into four groups in a way similar to that used in PET (1): high, high-average, lowaverage, and low transport. However, in the present study, we classified the patients using two different solutes: one using DIP creatinine at 240 min of the dwell, and the other using dialysate sodium concentration at 240 min of the dwell (DNa24O). Spearman non parametric measures of association and the chi-square test were used in the statistical analysis. Data are expressed as mean ± standard deviation, unless otherwise noted. Statistical significance was accepted ifp < 0.05. RESULTS The distribution of the dialysate sodium concentration at various dwell times and ofDIP sodium, DIP creatinine, and D/Do glucose at 240 min of the dwell are shown in Table 1. As shown in Table 2, dialysate sodium concentrations at various dwell times significantly corre lated with DIP creatinine and DIDo glucose at 240 min of the dwell. The correlation coefficients were higher with DNa24O as compared with the dialysate sodium concentrations at other dwell times. DNa24O also significantly correlated with intraperitoneal volume at 240 min. The correlations between dialysate sodium concentration and intraperitoneal volume at 240 min of the dwell were better and more significant than the correlation between D/Do glucose or DIP creatinine (at 240 min) and the intraperitoneal volume at 240 min of the dwell. DNa24O also significantly correlated with the sodium-sieving coefficient (S) and with the sodium diffusive transport coefficient (KED). At the earlier dwell times, dialysate sodium concentrations had better correlations with S, but weaker correlations with KED. Although DIP creatinine significantly
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for ultrafiltration failure stems from the abnormalities in water channels (20). In a previous study, we found that DIP sodium was significantly higher in high transporters than in low transporters (17). We also suggested that it might be possible to use DIP sodium for the classification of patients' transport characteristics, especially when using DIP values from the later part of the dwell with 3.86% glucose solution (during the period between 120 min and 360 min; better than values at 60 min or 90 min) (17). Because ultrafiltration (owing to the sodium sieving associated with convection) has a major impact on the sodium concentration in dialysate when using 3.86% glucose solution, and because the sodium concentration in commercial fresh dialysis solution is generally 132 mmol/L (close to that in blood), in the present study we further analyzed the possibility of using dialysate sodium concentration to classify patients' peritoneal transport characteristics.
correlated with KED creatinine, there was no significant correlation between DIP creatinine and S for creatinine. The plasma concentration of sodium was 140 ± 3.6 mmol/L (range: 133 -149.5 mmol/L). Unlike the strong correlation between dialysate creatinine concentration at 240 min and plasma creatinine concentration (r = 0.86), a weak though significant correlation existed between DNa24O and plasma sodium concentration (r = 0.41). The classifications using DIP creatinine and DNa24O are shown in Table 3. There were 6 high transporters, 17 high-average transporters, 14low-average transporters, and 9 low transporters with both methods. Although no significant difference was found between the two classification methods, some patients were partitioned into different groups by the two methods (especially the highaverage and lowaverage groups according to the PET method).
The present study shows that, as with DIP creatinine used in the standard PET test, dialysate sodium concentration at 240 min of a dwell using 3.86% glu cose dialysis fluid could be used to classify patients' peritoneal transport characteristics. The strong association found in the present study between DNa24O and the intraperitoneal volume at 240 min of the dwell is not unexpected. In a previous study, we demonstrated that peritoneal sodium transport is strongly related to peritoneal fluid re moval (17). It has recently been suggested that the transport of water devoid of solute across aquaporins is apparently the main reason for the sieving of sodium during peritoneal dialysis (21,27-29). Monquil et al reported on a selective decrease in ultrafiltra tion with normal glucose transport in a few CAPD patients (with loss of ultrafiltration capacity) who had minor declines of dialysate sodium concentra
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DISCUSSION
tion when using hypertonic glucose solution; it was suggested that these alterations were perhaps due to a reduced number ofultrasmall pores (19). There fore, the magnitude of the initial decrease in DIP values for sodium, using 3.86% glucose solution, has recently been suggested as an indicator of transcellular water transport through the ultrasmall pores (18,30). The significant correlation between DNa24O and the sodium-sieving coefficients (and creatinine as well) suggest that using DNa24O' we can also estimate the convective transport properties (and perhaps water-channel status) of the membrane, which could not be done by standard PET. Owing to the close link to the ultrafiltration process, it is not surprising that the correlation between DNa24O and intraperitoneal volume was better and more significant than the correlations between DIDo glucose (and DIP creatinine) and the intraperitoneal volume. Even though diffusive transport of sodium with current dialysis fluid composition is not the major transport component in peritoneal sodium transport (17), the present study shows that significant correlations exist between DNa24O and DIP creatinine or DIDo glucose, and, more importantly, that significant
to the small number of patients in the present study and the possible variation of dialysate sodium concentration in the fresh dialysate, further studies are needed to evaluate the clinical importance of this simplified classification method. ACKNOWLEDGMENT This study was supported by a grant from Baxter Healthcare Corporation, McGaw Park, Illinois, U.S.A. REFERENCES 1. Twardowski ZJ, Nolph KD, Khanna R, Prowant BF, Ryan LP, Moore HL, et al. Peritoneal equilibration test. Perit Dial Bull. 1987; 7:138-47. 2. Twardowski ZJ. Clinical value of standardized equilibration tests in CAPD patients. Blood Purif. 1989; 7:95-108. 3. Canada-U.S.A. (CANUSA) Peritoneal Dialysis Study Group. Adequacy of dialysis and nutrition in continuous peritoneal dialysis: Association with clinical outcome. J Am Soc Nephrol. 1996; 7:198-207. 4. Twardowski ZJ, Prowant BF, Nolph KD, Khanna R, Schmidt LM, Satalowich RJ. Chronic nightly tidal peritoneal dialysis. ASAIO Trans. 1990; 36:M584-8. 5. Nolph KD. Clinical implications of membrane transport characteristics on the adequacy of fluid and solute removal. Perit Dial Int. 1994; 14(Suppl 3):S78-82. 6. Burkart JM. Effect of peritoneal dialysis prescription and peritoneal membrane transport characteristics on nutritional status. Perit Dial Int. 1995; 15(5, Suppl): S20-35. 7. Heimbürger 0. Residual renal function, peritoneal transport characteristics and dialysis adequacy in peritoneal dialysis. Kidney Int. 1996; 50(Suppl 56):S47-55. 8. Heaf J. CAPD adequacy and dialysis morbidity: Detrimental effect of a high peritoneal equilibration rate. Ren Fail. 1995; 17:575-87. 9. Davies SJ, Phillips L, Russell GI. Peritoneal solute transport predicts survival on CAPD independently of residual renal function. Nephrol Dial Transplant. 1998; 13:962-8. 10. Wang T, Heimbürger 0, Waniewski J, Bergström J, Lindholm B. Increased peritoneal permeability is associated with decreased fluid and small solute removal and higher mortality in CAPD patients. Nephrol Dial Transplant. 1998; 13:1242-9. 11. Churchill DN, Thorpe KE, Nolph KD, Keshaviah PR, Oreopoulos DG, Page D. Increased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. J Am Soc Nephrol. 1998; 9:1285-92. 12. Lo WK, Brendolan A, Prowant BF, Moore HL, Khanna R, Twardowski ZJ, et al. Changes in the peritoneal equilibration test in selected chronic peritoneal dialysis patients. J Am Soc Nephrol. 1994; 4:1466-74. 13. Heimbürger 0, Wang T, Lindholm B. Alterations in wa ter and solute transport with time on peritoneal dialy
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correlations exist between DNa240 and diffusive mass transport coefficients for sodium and creatinine. These results suggest that DNa240 reflects in part the diffusive permeability of the peritoneal membrane and could thus be used as a marker to classify a patient's peritoneal diffusive transport characteristics. Although DIP sodium at 240 min of the dwell had better correlation with the fluid and other solute transport parameters, the differences were quite small. Note that dialysate sodium concentrations had weak correlations with the plasma sodium concentration, whereas a strong correlation existed between dialysate creatinine and plasma creatinine concentrations. This result suggests that although DIP for sodium is better than DNa240 in the correlation to solute transport and fluid transport, we can still use dialysate sodium concentration as a sufficiently accurate marker, whose use has the advantage of eliminating the need for blood sampling. Although the influence of plasma sodium concentration on the dialysate sodium concentration is less in the initial part of the dwell, our results indicate that the dialysate sodium concentration in the early dwell does not reflect the peritoneal membrane diffusive transport characteristics as well (compared to DNa240). We found no significant difference in the classification of patients' peritoneal transport using DIP crea tinine or DNa240. However, we noted that some patients may be allocated to different groups with these two methods; the different allocation mainly happened to high-average and low-average transporters. The clinical significance of the allocations needs further study to elucidate. Because inadequate fluid (and sodium) removal and inadequate blood pressure control are common problems in CAPD patients (31,32), the better prediction of peritoneal fluid removal and peritoneal sodium transport using DNa240 warrants us to speculate that the new classification method may have an important impact on measurements of adequacy of peritoneal dialysis. In summary, the present study suggests that dialysate sodium concentration at 240 min of a dwell using 3.86% glucose dialysis solution could be used to classify patients' peritoneal transport characteristics. The benefits (compared to standard PET) ofusing DNa240 to classify patients' peritoneal transport characteristics may include: (1) The better prediction, by DNa240' of peritoneal fluid transport than by D/D0 glucose and DIP creatinine. (2) The reflection, by DNa240' ofboth diffusive and convective transport. (3) A perhaps better understanding, enabled by DNa240 measurement, of the possible role of water channels in peritoneal fluid transport. Furthermore, DNa240 measurement does not suffer from interference with dialysate glucose and needs only one dialysate sample. On the other hand, owing
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sis. Perit Dial Int. 1999; 19(5uppl 2):83-90. 14. Heimbürger 0. Peritoneal transport in patients treated with continuous peritoneal dialysis [PhD Thesis] . Stockholm: Karolinska Institute; 1994. 15. Charra B, Calemard E, Ruffet M, Chazot C, Terrat JC, Vanel T, et al. Survival as an index of adequacy of di alysis. Kidney Int. 1992; 41:1286-91. 16. Nolph K, Sorkin M, Moore H. Autoregulation of sodium and potassium removal during continuous ambulatory peritoneal dialysis.ASAIO Trans. 1980; 26:334-8. 17. Wang T, Waniewski J, Heimbürger 0, Werynski A, Lindholm B. A quantitative analysis of sodium transport and removal during peritoneal dialysis. Kidney Int. 1997; 52:1609-16. 18. Ho-dac Pannekeet MM, Atasever B, Krediet RT. Analysis of ultrafiltration failure (UFF) in peritoneal dialysis (PD) patients [Abstract]. J Am Soc Nephrol. 1996; 7:1481. 19. Monquil MCJ, ImholzALT, Struijk DG, Krediet RT. Does impaired transcellular water transport contribute to net ultrafiltration failure during CAPD? Perit Dial Int. 1995; 15:42-8. 20. Ho-dac-Pannekeet MM, Atasever B, Struijk DG, Krediet RT. Analysis of ultrafiltration failure in peritoneal dialysis patients by means of standard peritoneal permeability analysis. Perit Dial Int. 1997; 17:144-50. 21. Rippe B. How to measure ultrafiltration failure: 2.27% or 3.86% glucose? Perit Dial Int. 1997; 17:125-8. 22. Heimbürger 0, Waniewski J, Werynski A, Lindholm B. A quantitative description of solute and fluid transport during peritoneal dialysis. Kidney Int. 1992; 41:1320-32. 23. Heimbürger 0, Waniewski J, Werynski A, Tranæus A, Lindholm B. Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity. Kidney Int. 1990; 38:495-506.
