Induction of chronic kidney failure in a long-term peritoneal exposure model in the rat: effects on functional and structural peritoneal alterations.

BACKGROUND: A long-term peritoneal exposure model has been developed in Wistar rats. Chronic daily exposure to 3.86% glucose based, lactate buffered, conventional dialysis solutions is possible for up to 20 weeks and induces morphological abnormalities similar to those in long-term peritoneal dialysis (PD) patients. The possible effects of kidney failure in this model are unknown. The aim was to analyze the effects of chronic kidney failure on peritoneal function and morphology, alone and in combination with PD exposure, in a well-established, long term, peritoneal exposure model in the rat. ♢ METHODS: 40 male Wistar rats were randomly assigned into four experimental groups: no nephrectomy, no peritoneal exposure (sham; n = 8); nephrectomy, no peritoneal exposure (Nx; n = 12); no nephrectomy, with peritoneal exposure (PD; n = 8); and nephrectomy, with peritoneal exposure (NxPD; n = 12). The nephrectomy consisted of a one-step 70% nephrectomy. The peritoneal exposure groups were infused once daily for 16 weeks with a 3.86% glucose-based dialysis solution. Development of chronic kidney disease was monitored during the experiment. Peritoneal function and morphological assessment of the peritoneal membrane were performed at the end of the experiment. ♢ RESULTS: During follow-up the nephrectomized groups developed uremia with remarkable renal tubular dilatation and glomerular sclerosis in the renal morphology. Functionally, uremia (Nx) and PD exposure (PD) alone showed faster small solute transport and a decreased ultrafiltration capacity, which were most pronounced in the combination group (NxPD). The presence of uremia resulted in histological alterations but the most severe fibrous depositions and highest vessel counts were present in the PD exposure groups (PD and NxPD). Significant relationships were found between the number of vessels and functional parameters of the peritoneal vascular surface area. ♢ CONCLUSION: It is possible to induce chronic kidney failure in our existing long-term peritoneal infusion model in the rat. The degree of impairment of kidney function after 16 weeks is comparable to chronic kidney disease stage IV. Uremia per se induces both functional and morphological alterations of the peritoneal membrane. An additive effect of these alterations is present with the addition of chronic kidney failure to the model. The latter makes the present long-term model important in better understanding the pathophysiology of the peritoneal membrane in PD.

The effects of a dialysis solution with a combination of glycerol/amino acids/dextrose on the peritoneal membrane in chronic renal failure.

BACKGROUND: Long-term peritoneal dialysis (PD) with conventional glucose based, lactate-buffered PD fluids may lead to morphological and functional alterations of the peritoneal membrane. It was hypothesized that long-term exposure to a different buffer and a mixture of osmotic agents would cause less peritoneal abnormality. OBJECTIVES: To investigate the effects of long-term exposure to a bicarbonate/lactate-buffered dialysis solution with a mixture of osmotic agents: glycerol 1.4%, amino acids 0.5%, and dextrose 1.1% (= 1% glucose) (GLAD) in a rat model with chronic kidney failure. METHODS: All rats underwent a peritoneal catheter implantation and a 70% nephrectomy. Thereafter, the rats were randomly divided into 3 groups: GLAD, 3.86% Dianeal (Baxter, Nivelles, Belgium), and buffer (Physioneal without glucose, Baxter). All rats were infused daily for 16 weeks with the appropriate PD fluid. Afterwards, a peritoneal permeability analysis (SPARa) was performed using 3.86% Physioneal in all groups. After the SPARa, the rats were sacrificed to obtain tissue samples for morphometric determinations. Omental tissue was stained with picro Sirius red for assessment of fibrosis and with CD31 for vessel density. RESULTS: GLAD and Dianeal showed faster small solute transport compared to the hypotonic buffer. No differences between the groups were present in ultrafiltration. Dianeal had the lowest value for free water transport and the highest protein clearances. Total triglyceride in plasma was not different between GLAD and the buffer. Vessel density after GLAD exposure (20 V/F) was very similar to the value found for the buffer solution (17 V/F); Dianeal caused a significantly higher value (35 V/F, p < 0.01). Also, the amount of fibrosis was higher in the Dianeal-exposed rats (p < 0.01). CONCLUSION: Both hypertonic dialysis solutions increased peritoneal solute transport. GLAD exposure was associated with the best preservation of peritoneal morphology. The results of GLAD were very similar to those of the bicarbonate/lactate-buffered solution without osmotic agents. Studies in humans are needed for further assessment of GLAD.

Addition of a nitric oxide inhibitor to a more biocompatible peritoneal dialysis solution in a rat model of chronic renal failure.

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.

Karl d. Nolph state of the art lecture: feasible and future options for salvation of the peritoneal membrane.

A review is given of the various available strategies that can be used to protect the peritoneal membrane. A discussion of experimental studies on approaches that are still experimental, but that might be applied in patients in the future, follows. The currently available approaches include dietary sodium restriction, use of high-dose loop diuretics and of inhibitors of the renin-angiotensin system. All should preferably be combined with a dialysis prescription aimed at reducing the patient's exposure to glucose and its degradation products. The experimental studies indicate favorable effects of combining osmotic agents, together with drugs that interfere with the polyol pathway and the formation of advanced glycosylation end-products.

Recombinant human soluble tumor necrosis factor-alpha receptor fusion protein partly attenuates ventilator-induced lung injury.

Ventilator-induced lung injury is mediated, at least in part, by TNF-alpha. We determined the effect of a recombinant human soluble TNF receptor fusion protein (etanercept) on mechanical ventilation (MV)-induced changes in a murine ventilator-induced lung injury model. After pretreatment with etanercept or placebo, C57Bl/6 mice were anesthetized and randomized to MV with either low tidal volumes (VT, approximately 7.5 mL/kg) or high VT ( approximately 15 mL/kg) for 5 h. Instrumented but spontaneously breathing mice served as controls. End points were lung wet-to-dry ratios, lung histopathology scores, protein levels, neutrophil cell counts and thrombin-antithrombin complex levels in bronchoalveolar lavage fluid (BALF), and cytokine levels in lung homogenates. The number of caspase 3-positive cells was used as a measure for apoptosis. Etanercept treatment attenuated MV-induced changes, in particular, in MV with high VT. Compared with placebo, etanercept reduced the number of neutrophils in BALF and thrombin-antithrombin complex levels in BALF and cytokine levels in lung homogenates. Lung wet-to-dry ratios, histopathology scores, and local protein levels in BALF, however, were not influenced by etanercept treatment. The number of caspase 3-positive cells was significantly higher in etanercept-treated animals. Inhibition of TNF by etanercept attenuates, in part, MV-induced changes.

A pyruvate-buffered dialysis fluid induces less peritoneal angiogenesis and fibrosis than a conventional solution.

BACKGROUND: Conventional lactate-buffered peritoneal dialysis (PD) fluids containing glucose and glucose degradation products are believed to contribute to the development of fibrosis and angiogenesis in the dialyzed peritoneum. To reduce potential negative effects of lactate, pyruvate was substituted as a buffer and its effects on peritoneal pathological alterations were studied in a chronic peritoneal exposure model in the rat. METHODS: 20 Wistar rats were infused intraperitoneally with pyruvate-buffered (n = 9) or lactate-buffered PD fluid. After 20 weeks of daily infusion, peritoneal function was assessed. In omental peritoneal tissue, the number of blood vessels was analyzed following alpha-smooth muscle actin staining. The degree of fibrosis was quantitated in Picro Sirius Red-stained sections and by assessment of the hydroxyproline content. Plasma lactate/pyruvate and betahydroxybutyrate/acetoacetate (BBA/AA) ratios were determined. Plasma and dialysate vascular endothelial growth factor (VEGF) levels were quantitated by ELISA. RESULTS: The mass transfer area coefficient of creatinine was higher and the dialysate-to-plasma ratio of sodium was lower in pyruvate-treated animals compared to the lactate-treated group (0.11 vs 0.05 mL/min, p < 0.05, and 78% vs 89%, p < 0.05). The BBA/AA ratio tended to be lower in the pyruvate animals (p = 0.07). The number of blood vessels was lower in pyruvate-treated animals (16 vs 37 per field, p < 0.001). Total surface area, luminal area, and wall/total area of the vessels were larger in the pyruvate group. The degree of fibrosis was lower in intersegmental and perivascular areas of pyruvate-exposed animals. Effluent VEGF was higher in the pyruvate group. CONCLUSIONS: Replacement of lactate by pyruvate resulted in changes in peritoneal solute transport, accompanied by a reduction in both peritoneal membrane angiogenesis and fibrosis, suggesting potentially novel mechanisms to reduce glucose-driven alterations to the peritoneal membrane in PD patients.

Pulmonary coagulopathy as a new target in lung injury--a review of available pre-clinical models.

Despite recent advances in supportive care, acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are clinical entities with high morbidity and high mortality. In systemic inflammation, like sepsis, uncontrolled host defense can lead to systemic activation of coagulation on the one hand, and attenuation of fibrinolysis on the other. In ALI/ARDS similar but local disturbances in fibrin turnover occur, leading to excessive alveolar fibrin deposition compromising pulmonary integrity and function. Therapies in patients with sepsis have specifically focused on coagulation disturbances. Evidence from preclinical and clinical investigations suggests pharmacologically targeting pulmonary "coagulopathy" could be of benefit to patients with ALI/ARDS as well. Recent animal studies have demonstrated that administration of heparins, activated protein C (APC), Antithrombin (AT), Tissue factor-Factor VIIa (TF-FVIIa) pathway inhibitors, plasminogen activators (PA) and thrombomodulin (TM) can attenuate pulmonary coagulopathy and reduce lung injury and/or improve oxygenation. Some of these studies have also shown anti-inflammatory effects of treatment targeting at coagulation. To date there are no published studies that have specifically studied the effects of anticoagulants on ALI/ARDS however there are on-going clinical trials. A solid base has to be provided by preclinical studies to justify clinical studies on new pharmacologic therapies for ALI/ARDS. In this systematic literature review we give an overview of the models for ALI/ARDS that have been used so far on the topic of pulmonary coagulopathy and focus on the pharmacological interventions that have been evaluated with these models. Finally, the applicability of the different approaches for future research on this subject will be discussed.

The relationship between effluent potassium due to cellular release, free water transport and CA125 in peritoneal dialysis patients.

Background. Recently, we found evidence of effluent potassium (K(+)) additional to diffusion and convection, suggesting cellular release (CR). Its relationship with free water transport (FWT) in stable peritoneal dialysis (PD) patients suggested an effect of hypertonicity of the dialysis solution leading to cell shrinkage. The aim of the present study was to reproduce these findings in groups according to PD duration and to further investigate the role of mesothelial cells in the observed phenomenon. Methods. Standard peritoneal permeability analyses done with 3.86% glucose were analysed cross-sectionally in three different groups: short-term (n = 53) 0-2 years PD treatment; medium-term (n = 24) 2-4 years PD and long-term (n = 26) > 4 years PD. Results. The time courses for FWT and cellular release of K(+) (CR-K(+)) during the dwell were not significantly different among the groups. Cancer antigen (CA) 125 was highest in the short-term group (P ≤ 0.02) and had a strong positive correlation with mass transfer area coefficient of creatinine (MTAC-creatinine) only in the short-term group (r = 0.62, P ≤ 0.01). CA125 had no relationship with either CR-K(+) or FWT, except for negative relationships in the short-term group (CR-K(+), r = -0.41, P ≤ 0.05; FWT, r = -0.54, P ≤ 0.05). Conclusion. We conclude that the correlation of CA125 and MTAC-creatinine is dependent on PD duration and underlines the in vitro observation that mesothelial cells produce vasoactive substances that may increase the peritoneal surface area. However, CA125 is not directly related to CR-K(+) or FWT. Therefore, the relationship between FWT and CR-K(+) is likely to reflect hypertonic cell shrinkage, regardless of the duration of PD, and confirms our earlier findings.

Effects of reducing the lactate and glucose content of PD solutions on the peritoneum. Is the future GLAD?

Background. Long-term peritoneal dialysis (PD) may lead to functional and morphologic changes in the peritoneal membrane, probably because of the continuous exposure to conventional dialysis solutions. Methods. The morphologic changes include neoangiogenesis and fibrosis. The authors of this article developed a long-term peritoneal exposure model in rats, in which the morphological alterations could be induced after daily peritoneal infusion of a 3.86% glucose/lactate-buffered conventional PD solution. Results and Conclusions. In the present article, a review of the model and of the results obtained with various available and experimental solutions is given. It appeared that high lactate concentrations contributed to the glucose-induced neoangiogenesis by pseudohypoxia. Glucose degradation products were probably more important in the induction of peritoneal fibrosis. The promising results of a combination of amino acids, glycerol and glucose, each in a low concentration, buffered with either pyruvate or bicarbonate/lactate, are presented and discussed. The combination of glycerol, amino acids and dextrose, dissolved in a bicarbonate/lactate buffer (GLAD), may be an option for a new generation of dialysis fluids.

Free water transport, small pore transport and the osmotic pressure gradient.

BACKGROUND: Water transport in peritoneal dialysis (PD) patients occurs through the small pores and water channels, the latter allowing free water transport (FWT). The osmotic gradient is known to be one of the major determinants of water transport. The objective of the study was to analyse the relation between each transport route and the osmotic gradient. METHODS: The 4-h standard peritoneal permeability analyses of 80 stable PD patients were studied. Small pore transport (SPT) was calculated based on the transported amount of sodium. FWT was calculated by subtracting SPT from transcapillary ultrafiltration (TCUF). Water transport rates were determined. The osmotic gradient was calculated. The slope of the relation between FWT rate and osmotic gradient (slope(FWT)), and the elimination constant (K(e)) of the exponential relation between SPT rate and osmotic gradient (K(SPT)) were calculated for every patient. RESULTS: The FWT rate was related to the osmotic gradient (P = 0.001). A similar correlation was also found between the SPT rate and osmotic gradient when fitted exponentially (P = 0.005). The rates of FWT decreased significantly between each time point during the whole dwell. The SPT rates decreased significantly within the first half of the dwell and levelled off thereafter. No correlations were found between the slope(FWT), K(SPT) and PD duration. The slope(FWT) of the relationship between the FWT and the osmotic gradient is an indirect measurement of the amount of functioning water channels. Similarly, the K(SPT) value represents the number of functioning small pores. The absence of a relationship of these parameters with the duration of PD suggests opposing mechanisms, for instance a lower number of functioning pores in combination with an increased vascular surface area. Conclusion. The curves of the relationship between FWR, SPT and OG support the assumption that FWR is much more dependent on the OG than SPT. Non-osmotic determinants are likely to be important in small pore fluid transport.

Developing specific therapeutic strategies for transfusion-related acute lung injury. An overview of potentially useful animal models.

Transfusion-related (TR)- acute lung injury (ALI) is the leading cause of transfusion-related morbidity and mortality. The pathogenesis of TRALI is thought to be a "two hit"-entity: the "first hit" is (any) proinflammatory pulmonary condition (e.g., pneumonia, sepsis or lung contusion) resulting in activation of lung endothelium with sequestration of polymorphonuclear neutrophils - the "second hit" is provided by transfusion of a blood product. Either antibodies against neutrophils are thought to be implicated in the activation of the sequestrated neutrophils, or bioactive lipids (which accumulate during storage of blood products) induce the "second hit", finally resulting in lung injury. Preventive measures do not prevent all TRALI cases. Also, TRALI is most probably underdiagnosed. In this review, we call for the development of therapeutic approaches for this potentially life-threatening disease. Several interventions which are beneficial in ALI and may also be beneficial in TRALI are discussed. The application of these interventions requires the development of clinically relevant TRALI animal models. We discuss the present TRALI animal models and their shortcomings and propose future animal models, in which clinically relevant "first hits" can be applied, thereby imitating the complex clinical situation.

Does the biocompatibility of the peritoneal dialysis solution matter in assessment of peritoneal function?

BACKGROUND: Peritoneal function tests are performed in peritoneal dialysis (PD) patients to characterize peritoneal membrane status. A low pH/high glucose degradation product (GDP) dialysis solution is used as the test solution. The objective of the present study was to compare a 3.86% glucose, low pH/high GDP dialysis solution (pH 5.5) with a 3.86% glucose, normal pH/low GDP dialysis solution (pH 7.4) in assessments of peritoneal membrane function. METHODS: Two standard peritoneal permeability analyses (SPA) were performed in 10 stable PD patients within 2 weeks. One SPA was done with the 3.86% low pH/high GDP solution, and the other with the 3.86% normal pH/low GDP solution. The sequence of the two tests was randomized. RESULTS: Fluid transport parameters and glucose absorption were not different between the two groups. No differences were found for the mass transfer area coefficients (MTACs) of low molecular weight solutes calculated over the whole dwell. However, MTAC urea in the first hour of the dwell was higher in the test done with low pH/high GDP dialysate, suggesting more peritoneal vasodilation. No difference was found in protein clearances. Sodium sieving at multiple time points during the dwell was similar with the two solutions. CONCLUSION: The results obtained with the glucose-containing normal pH/low GDP dialysis solution were similar to those obtained with the glucose-containing low pH/high GDP dialysate in assessments of peritoneal membrane function.

Apparent successful mesothelial cell transplantation hampered by peritoneal activation.

BACKGROUND: Mesothelial cell transplantation has been suggested to improve mesothelial repair after surgery, recurrent peritonitis and peritoneal dialysis. METHODS: In this study we evaluated mesothelial cell transplantation during the resolution phase of experimentally thioglycollate-induced peritonitis in rats. To this end 4 x 10(6) DiO-labeled autologous mesothelial cells were transplanted 1 week after peritonitis induction. Peritoneal inflammation and permeability characteristics were evaluated after another week. RESULTS: Mesothelial cell transplantation after peritonitis resulted in incorporation of these cells in the parietal mesothelial lining, leading to an acute transient submesothelial thickening which was not seen in transplanted animals without prior peritonitis induction. Long-term functioning of these repopulated mesothelial cells leaded to peritoneal activation as evidenced by a approximately twofold increase in peritoneal lymphocytes (P < 0.01) and omental mast cell counts (P < 0.05), accompanied by the induction of inflammation markers monocyte chemoattractant protein-1 (MCP-1) (P < 0.01) and hyaluronan (P < 0.01) in the transplanted peritonitis group, but not in rats with peritonitis without mesothelial cell transplantation or in control rats without mesothelial cell transplantation (all four parameters P < 0.01). In addition, trapping of transplanted mesothelial cells in the milky spots of omental tissue and lymphatic stomata of the diaphragm both in control and thioglycollate rats seems to increase microvascular permeability, reflected by apparent increased diffusion rates of small solutes and proteins. CONCLUSION: Altogether, our data underscore the importance of controlling peritoneal (patho)physiology and function in mesothelial transplantation protocols.

The contribution of free water transport and small pore transport to the total fluid removal in peritoneal dialysis.

BACKGROUND: Water transport in peritoneal dialysis (PD) patients is across the small pores and water channels, the latter allowing free water transport. The objective of the study was to investigate the contribution of each transport route on transcapillary ultrafiltration (TCUF). METHODS: Standard peritoneal permeability analyses of 80 stable PD patients were analyzed. Twenty-nine patients were followed longitudinally. Fluid transport through small pores (SPT) was assessed by the amount of transported sodium. Free water transport (FWT) was calculated by subtracting SPT from TCUF. The contribution of FWT and SPT to the TCUF and water transport rates at any time point was computed. RESULTS: The ultrafiltered volume due to SPT increased gradually during the dwell, while FWT reached its maximum around 3 hours. The rate of FWT decreased continuously during the dwell. SPT decreased during the initial 2 hours and remained stable thereafter. At 60 minutes, the SPT (P < 0.05) and its contribution (P < 0.05) were positively related to the MTAC(creat). The contribution of FWT after 1 hour, but not the absolute amount, showed an inverse relationship. Peritoneal solute transport parameters (P < 0.01) and the contribution of SPT (P= 0.08), but none of the other fluid parameters showed a U-shape with the lowest values in the second year of PD (P < 0.01). CONCLUSION: The dwell courses of water transport suggest that the activity of water channels is dependent and limited by the crystalloid osmotic pressure gradient, while other determinants are important in SPT. The time-course of SPT paralleled that of peritoneal solute transport parameters.

Determinants of peritoneal solute transport rates in newly started nondiabetic peritoneal dialysis patients.

OBJECTIVE: An overrepresentation of a fast peritoneal transport status in new peritoneal dialysis (PD) patients with extensive comorbidity has been reported in some studies. High mass transfer area coefficients (MTACs) of low MW solutes suggest the presence of a large effective peritoneal surface area. The mechanism is unknown. It might include comorbidity, chronic inflammation, or an effect of mesothelial cell mass on peritoneal transport by the production of vasoactive substances. To investigate their relative importance in early PD, peritoneal permeability characteristics in incident PD patients were analyzed for relationships with comorbidity, serum concentrations of inflammatory markers, and products of the mesothelial cells that can be detected in dialysate. DESIGN: A cross-sectional study. SETTING: A university hospital. METHODS: 46 patients who fulfilled the following inclusion criteria were analyzed: a standard peritoneal permeability analysis (SPA) within 6 months after the start of PD, no peritonitis prior to the SPA, older than 18 years, and without diabetes mellitus as a primary renal disease. The patients were divided into tertiles based on the MTAC creatinine: slow, medium, and fast transport groups. The Davies comorbidity score was used to assess comorbidity. Serum and dialysate samples obtained during the SPA were used to determine hyaluronan, interleukin (IL)-6, vascular endothelial growth factor (VEGF), and cancer antigen 125 (CA125). The dialysate concentrations of these substances were expressed as their dialysate appearance rates. RESULTS: No significant differences were present in the three transport groups for comorbidity, serum concentrations of inflammatory markers, or serum VEGF. Interleukin-6 and VEGF concentration attributed to local VEGF production were not different between the tertiles. Levels of VEGF were higher in the medium transport group compared to the slow transport group (p = 0.02); CA125 was higher in the fast transport group compared to the medium transport group (p= 0.01). When analyzed as continuous variables, MTAC creatinine was related to VEGF (r= 0.33, p < 0.05) and CA125 (r= 0.41, p = 0.03). In linear regression analysis, VEGF influenced the association between CA125 and MTAC creatinine; IL-6 weakened this association only marginally. CONCLUSION: A fast peritoneal transport status in incident nondiabetic PD patients was not related to comorbidity. The relationships found between VEGF, CA125, and MTAC creatinine may suggest a role of VEGF in the regulation of the vascular peritoneal surface area, possibly already before structural abnormalities have developed. Our analyses are consistent with the hypothesis that mesothelial cell mass is an important determinant of the peritoneal transport status in incident nondiabetic PD patients without previous peritonitis. Of the many potential mediators produced by mesothelial cells, VEGF was more important than the inflammation marker IL-6.

Does lymphatic absorption change with the duration of peritoneal dialysis?

BACKGROUND: Ultrafiltration failure is an important complication of long-term peritoneal dialysis (PD). A high effective lymphatic absorption rate (ELAR) can contribute to impaired ultrafiltration. It is unknown whether the ELAR increases with time on PD. OBJECTIVE: The relationship between the ELAR and duration of PD was analyzed, as well as the correlation between the ELAR and other transport parameters. We also studied the relation between the ELAR and cancer antigen 125 (CA125) a marker for mesothelial cell mass. SETTING: Peritoneal dialysis unit in the Academic Medical Center, Amsterdam. DESIGN: Cross-sectional and longitudinal studies of standard peritoneal permeability analyses (SPAs; 4-hour dwells, dextran 70 as a volume marker) with glucose 3.86% in 130 PD patients. METHODS: SPAs were analyzed in 130 stable PD patients (77 males). Median duration of PD was 25 months (range 1-214) in a cross-sectional study. The last SPA from each patient was analyzed. The longitudinal analysis included 24 patients (12 males) from whom at least 3 SPAs were available with a minimum interval of 8 months. Dextran 70, 1 g/L, was administered intraperitoneally at the initiation of the test. Lymphatic absorption was calculated from the disappearance rate of dextran 70 during the 4-hour dwell. Therefore, the ELAR included both transmesothelial and subdiaphragmatic uptake of dextran 70. RESULTS: Median ELAR was 1.43 mL/minute (range 0.17- 6.59 mL/minute). No relationship was found between the ELAR and duration of PD in the cross-sectional analysis, nor was there a trend in time for 20 of the 24 patients studied longitudinally. In 4 patients, a negative trend was found. None of these had ultrafiltration failure and all 4 patients had a different cause for end-stage renal failure. The ELAR was correlated with parameters of peritoneal solute transport, but not with CA125 when investigated in a cross-sectional analysis. Only after 48 months of PD treatment was a significant relationship between the ELAR and CA125 seen (r = 0.46, p < 0.05). CONCLUSIONS: No time trend is present for the effective peritoneal lymphatic absorption rate, and it is not associated with patient or technique survival. Although increased lymphatic absorption is one of the causes of ultrafiltration failure, it is unlikely to contribute to the development of ultrafiltration failure in long-term PD patients with well-maintained transcapillary ultrafiltration.

Diffusion correction of sodium sieving applicable in a peritoneal equilibration test.

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.