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COMMENTARY |
Division of Nephrology Department of Medicine Academic Medical Center University of Amsterdam Amsterdam, The Netherlands
e-mail: c.n.deboer{at}amc.uva.nl
The rationale for the development of the so-called biocompatible dialysis solution is the observation that severe peritoneal abnormalities may develop in long-term peritoneal dialysis (PD) patients. Exposure to conventional dialysis solutions is likely to be one of the pathogenetic factors. Ultrafiltration failure is the most common clinical manifestation of a damaged peritoneal membrane. All biocompatible solutions have reduced concentrations of glucose degradation products (GDPs) and, in some, the lactate buffer is partially or totally replaced by bicarbonate.
Long-term exposure to some of these biocompatible solutions in rats has shown an attenuation of fibrosis and neoangiogenesis compared with conventional fluids (1–3). A patient was recently described who was treated for 4 years with low-GDP neutral-pH solutions and did not develop any morphological or functional peritoneal abnormality (4).
A number of controlled observational follow-up studies on biocompatible dialysis fluids with various designs and solutions have been published (5–12). With the exception of the study by Rippe et al. (7), duration of treatment ranged from 2 months to 1 year. Three studies were done in incident patients (10–12), the others were in prevalent patients or a mixture of both (5–9). A somewhat better ultrafiltration was reported in only one study (6). None of the others found differences in the time-course of solute or water transport between the biocompatible and the conventional solutions during a standardized 4-hour dialysis exchange. This is not unexpected because the peritoneal abnormalities seen in long-term patients take some years to develop.
Acute exposure to a dialysis solution in rats causes transient increases in peritoneal arteriolar blood flow and leads to capillary recruitment, which may result in a larger effective peritoneal surface area during the initial phase of an exchange (13). The effects were especially dependent on the dialysate glucose concentration, the lactate buffer, and the concentration of GDPs. This raises the question of whether the reduced vasoactivity of biocompatible solutions could influence peritoneal transport as measured during a standardized 4-hour dwell, such as the peritoneal equilibration test (PET) or one of its modifications. No differences were found in baseline PETs between patients treated with biocompatible solutions and the controls in the above discussed studies (5–9,11,12), with the exception of one (10), in which a lower ultrafiltration was reported in patients investigated with a bicarbonate-buffered solution (glucose concentration 2.5%) compared with those examined using a conventional dialysis fluid. No difference was present for the dialysate-to-plasma ratio (D/P) of creatinine. A study in children using a 3.86% glucose PET with dextran 70 as volume marker found no significant differences between patients investigated with a bicarbonate/lactate-buffered solution and a historic control group in which a PET with a conventional solution had been done (14).
It is evident that the most accurate results are obtained when paired observations are used, that is, when patients serve as their own controls. Six studies using this approach have been published (5,15–19), two of which were in children (16,17). No difference in solute transport was found in any of the investigations. Three studies used a 1.36%/1.5% glucose solution. No effect of the biocompatible solution on net ultrafiltration was detected in any of those studies (5,15,16). Similar results were obtained in the two studies using a 3.86% glucose solution (5,18). However, one recently published study reported a somewhat lower net ultrafiltration when a 2.5% glucose bicarbonate/lactate solution was compared to a conventional one (19). This finding is in accordance with a previously mentioned study from Spain (10) but is in contrast to the other studies using a 2.27%/2.5% glucose concentration (6–8). Summarizing, the studies on the possibility of an acute effect of biocompatible dialysis solutions on peritoneal transport using a 4-hour dwell show no effect on solute transport. No effect on ultrafiltration could be demonstrated when a 1.36%/1.5% glucose solution was used, nor for a 3.86%/4.25% glucose solution. The results obtained with the 2.27%/2.5% glucose solution are equivocal. A possible explanation may be that the ultrafiltration induced by osmosis is very low for the 1.36%/1.5% solutions, making it impossible to detect an ultrafiltration difference caused by the initial peritoneal vasodilation. Likewise, the ultrafiltration induced by the 3.86%/4.25% glucose concentrations may be so high that an effect of vasodilation is overshadowed.
An interesting hypothesis on how biocompatible solutions might influence ultrafiltration has been developed by La Milia et al. and is published in this issue of Peritoneal Dialysis International (20). It is based on the notion that dissociation of sodium chloride is incomplete at a normal pH. A low pH is required to reach complete dissociation into Na+ and Cl–. The authors postulated that all sodium is present in its ionic form in conventional dialysis solutions due to their low pH, but that this is not the case for biocompatible solutions with a normal pH. A lower concentration of ionized sodium will have a negative effect on water transport induced by crystalloid osmosis. Therefore, the authors measured total sodium by flame photometry and ionized sodium by a direct ion-selective electrode in a conventional 3.86% glucose solution and in a biocompatible solution with a pH of 7.4. The study was done in 13 continuous ambulatory PD patients that were investigated with both solutions after an interval of 48 hours. As expected, the concentrations of total and ionized sodium were not different before inflow of the acidic conventional solutions, but a mean difference of 5.1 mmol/L between total and ionized sodium was present in the lactate/bicarbonate-buffered solution. However, the difference between the conventional and the biocompatible solutions disappeared immediately after inflow, probably due to mixing with the residual volume after drainage of the preceding exchange. This may explain why, also in this study, no difference in ultrafiltration was found between the biocompatible and the conventional solution when 3.86% glucose was used as osmotic agent.
What are the implications for the assessment of peritoneal transport using a PET or a PET-like test? The International Society for Peritoneal Dialysis (ISPD) Committee on Ultrafiltration Failure recommended using the modified PET for the detection of ultrafiltration failure. These guidelines were published in 2000 (21). The main difference with the standard PET is the use of a 3.86%/4.25% glucose solution and assessment of sodium sieving; changing to 3.86%/4.25% glucose has no effect on D/P creatinine (22). The absence of a measurable effect of the biocompatibility of a dialysis solution on ultrafiltration when the modified PET is employed strengthens the ISPD recommendation. The best available method should be used to detect differences between conventional and biocompatible solutions in the time-course of peritoneal transport that may arise during long-term treatment.
DISCLOSURE
The peritoneal dialysis research program is financially supported by Baxter and the Dutch Kidney Foundation.
REFERENCES
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