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Biocompatible dialysis solutions have been developed to preserve peritoneal membrane morphology and function. Compared with a conventional solution, a combination of glycerol, amino acids, and dextrose in a bicarbonate/lactate buffer (GLAD) led to less peritoneal fibrosis and fewer vessels in a chronic peritoneal exposure model in the rat. However, no concomitant reduction in small-solute transport was observed. We hypothesized that this result could be attributable to peritoneal vasodilation induced by vasoactive substances such as nitric oxide. The aim of the present study was to investigate whether fast transport of small solutes and proteins induced by exposure to GLAD could be influenced by Ngamma -methyl-L-arginine acetate (L-NMMA), an inhibitor of NO. These investigations used our rat model of long-term peritoneal exposure with chronic renal failure. All rats underwent peritoneal catheter implantation and a 70% nephrectomy. Thereafter, the rats were allocated to 3 groups: 16 weeks of peritoneal exposure to GLAD and L-NMMA, to GLAD only, or to buffer (bicarbonate/lactate without any osmotic agent). Afterward, a standard peritoneal permeability analysis adjusted for the rat was performed. Subsequently, the rats were euthanized, and tissue samples were obtained for morphometric determinations. No effect of L-MNNA on the transport of small solutes and proteins was found. Also, no effect on morphology was found. Our findings make it unlikely that NO is directly involved, being more in favor of a direct effect of amino acids on peritoneal transport.

Chronic exposure to peritoneal dialysis (PD) solutions is associated with a low-grade local inflammatory state of the peritoneum. The occurrence of culture-negative peritonitis in some PD patients treated with icodextrin focused our interest on subclinical inflammation in icodextrin-treated patients without peritonitis. The aim of the present study was to compare signs of inflammation in icodextrin-treated patients with the same signs in patients using glucose/lactate-based (GL) dialysis solutions only. Overnight PD effluents from 19 patients treated with icodextrin and 19 patients treated with GL were investigated for leukocyte count (LC) and differentiation (LD), and for dialysate concentrations of cancer antigen 125 (CA125, the marker of mesothelial cell mass) and hyaluronan (marker of inflammation and tissue remodeling in the peritoneal cavity). Blood cell counts and serum dextran antibodies (DA) were also determined. Total LC in the GL group was significantly lower than that in the icodextrin group. The LD was not different between the two groups, except for the percentage of eosinophils. The blood cell count did not differ between the groups. The median value of DA was similar in both groups. The hyaluronan concentration was markedly higher in the icodextrin group. No significant difference was found for dialysate CA125. In conclusion, the higher effluent cell count, higher percentage of eosinophils, and higher effluent hyaluronan levels in icodextrin-treated patients are consistent with a greater degree of subclinical inflammation during icodextrin treatment than during GL treatment.

The dialysate concentration of cancer antigen 125 (CA125) can be considered a reflection of mesothelial cell mass or turnover in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The effect of dwell times exceeding 4 hours on CA125 appearance rate (CA125AR) is not known. Therefore, our objective in the present study was to analyze the effect of dwell time on CA125AR in stable CAPD patients. In 43 stable CAPD patients, we analyzed standard peritoneal permeability analyses (SPAs) performed with a 3.86% glucose dialysate, and night-dwell effluents from the night dwell prior to the SPA. Dialysate CA125 concentration was measured by radioimmunoassay (RIA II: Fujirebio Diagnostics, Malvern, PA, U.S.A.). Night-dwell CA125 correlated with the duration of the dwell (r = 0.32, p = 0.04) and with the CA125 concentration in the 4-hour dwell (r = 0.83, p < 0.001). The mean CA125AR in the SPA effluent was 97.8 +/- 46.3 U/min; in the overnight effluent, it was 108.8 +/- 73.7 U/min (nonsignificant). A good correlation was present between the CA125AR in the 4-hour dwells and in the overnight dwells (r = 0.82, p < 0.001). We conclude that using night dwells to regularly assess dialysate CA125--for instance, at every out-patient visit--is possible in CAPD patients, provided that appearance rate is calculated.

Sodium sieving is a measure of free water transport. However its assessment is disturbed when a large difference exists between sodium concentrations in plasma and in dialysate--that is, when the diffusion rate is high. Based on previous findings concerning similarity in the mass transfer area coefficients (MTACs) of sodium and urate, we developed a model that corrects for high diffusion. The model enabled us to predict the dialysate sodium concentration resulting from diffusion alone at any time point during a dwell. The correction was based on knowledge of the intraperitoneal volume at any time point during the dwell, which can be calculated by using a volume marker (reference method). However, in a peritoneal equilibration test (PET), only the drained volume after 4 hours is available, and urate concentration is not routinely measured. Therefore, our objective in the present study was to investigate whether a diffusion correction using the MTAC of creatinine and the drained volume at the end of the dwell would be as accurate in estimating maximum sodium sieving as the reference method is. We analyzed standardized 4-hour dwells in 28 patients, 19 with stable PD and 9 with ultrafiltration failure. The dialysate consisted of a 3.86% glucose-containing solution to which dextran 70 was added as a volume marker. The correlation coefficient between the PET correction method and the reference method was 0.92 in all patients [0.90 in stable patients and 0.95 in the patients with ultrafiltration failure (p < 0.01 for all)]. We conclude that a diffusion correction for sodium can be made using PET data. A diffusion correction yields a better estimate of sodium sieving than does the sole use of the lowest dialysate-to-plasma (D/P) sodium irrespective of diffusion rate.

Peritoneal mesothelial cells are important for local host defense and membrane integrity. Dialysate cancer antigen 125 (dCA125) has been shown to be a good marker for the mesothelial cell mass in adult peritoneal dialysis (PD) patients. In children on PD, no information is available yet. We measured dCA125 in 65 dialysate samples from 24 PD children with a median age of 9.2 years (range: 2-18 years) and a median treatment time of 2.6 years (range: 0.1-9.3 years) on PD. The median dCA125 concentration was 8 U/mL (range: 2.3-30.7 U/mL), and the CA125 appearance rate (CA125AR) was 66.5 U/min/1.73 m2 (range: 18-282 U/min/1.73 m2). On cross-sectional analysis, a negative correlation was found between dCA125 and duration of PD treatment (r = -0.3, p = 0.04). No relation was found between age and dCA125 or CA125AR when the first measurement from each child was considered. No correlation was found between dCA125 and the mass transfer area coefficient of creatinine (MTACcreat). Longitudinal analysis showed a negative trend in CA125AR with duration of PD treatment (p = 0.03). No relation was found between peritonitis incidence and dCA125 or CA125AR. In conclusion, no influence of age on dCA125 and CA125AR was found. Levels of dCA125 declined with the duration of PD treatment, reflecting mesothelial cell mass, but they did not correlate with the MTACcreat or the peritonitis incidence in stable PD children.

Transcellular water transport (TCWT) can be estimated by Na- sieving. However, the assumption that the initial Na+ dialysate concentration (D0) is equal to the initial plasma concentration (P0) is not true for each patient. The difference leads to Na+ diffusion from the circulation to the dialysate, which diminishes the Na+ sieving. A model was developed to distinguish transcellular water transport from Na+ diffusion. We previously found evidence that the mass transfer area coefficient of urate (MTACurate) was similar to the MTACNa+. The MTAC is the product of the elimination constant (ke) and the volume of distribution (VD), the mean intraperitoneal volume. Because VD is known, the ke Na+ in each patient can be equated with the ke urate. The Na+ mass transfer from the circulation to the dialysate by diffusion can then be calculated for any time point during a dwell (Dt). Dt was subtracted from the measured Na+ dialysate concentration at 60 minutes. The corrected D/P Na+ then represents the actual Na+ sieving. Using 3.86% glucose dialysate, this approach was investigated in 15 stable peritoneal dialysis (PD) patients (normUF) and in 9 PD patients with low ultrafiltration (lowUF, < 400 mL/4 hours). The MTACurate was calculated according to Waniewski (W) and according to the Garred model (G). Similar calculations were also performed for the MTAC of creatinine (MTACcreat). Initial D/P Na+ was not different between the groups. When no diffusion correction was made, D/P60 Na+ in the lowUF group (median 0.898, range 0.870-0.949) was significantly higher (p < 0.025) than D/P60 Na+ in the normUF group (median 0.881, range 0.816-0.899). The difference disappeared after diffusion correction regardless of the correction model applied. However, at 240 minutes, D/P Na+ in the normUF group was significantly lower than in the lowUF group (median 0.880, range 0.839-0.952 vs median 0.942, range 0.866-0.987; p < 0.004). Even after correction, D/P Na+ in the normUF group was significantly lower: 0.847 normUF versus 0.893 lowUF (Wurate, p < 0.005); and 0.842 normUF versus 0.890 lowUF (Gcreat, p < 0.003). The correlation between the Wurate (the best theoretical diffusion correction) and Gcreat (the least) was: y = 0.99x + 0.0037. Furthermore, Bland and Altman analyses of Wurate and Gcreat at both 60 and 240 minutes resulted in random distribution around the means, with a slight overestimation in relation to the magnitude of Gcreat, as was expected. Gcreat can be used to make an accurate estimation of the contribution of Na+ diffusion in the time course of D/P Na+. It provides a simple way to more precisely determine Na+ sieving, and therefore TCWT. In conclusion, to avoid overestimation of impaired channel-mediated water transport, a Na+ diffusion correction should be made when D0 is not equal to P0 or in the case of a large vascular surface area.

To study the long-term effects of dialysis fluids on the peritoneal cavity, an in vivo model for continuous peritoneal dialysis in rats was developed. Mini vascular access ports were implanted subcutaneously in the neck of the rats and an attached catheter was instilled into the peritoneal cavity. Rats were injected daily with 10 mL of standard 3.86% Dianeal or saline for a period up to 12 weeks. In the peritoneal cavity an initial increase in total cells was observed after 4 weeks of fluid instillation. This had declined after 12 weeks. A similar trend was also seen for macrophage and neutrophil numbers, whereas the percentage of lymphocytes kept increasing in time. An effect of fluid instillation was observed on the density and the morphology of the mesothelial monolayer of the rats. A higher density of cells was observed after 12 weeks, and foci of young mesothelial cells within activated mesothelium were found. The results show that the rat model presented can be compared with the situation in the peritoneal cavity of continuous ambulatory peritoneal dialysis (CAPD) patients, and therefore is suitable for intervention studies.