Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels.

BACKGROUND: In a randomized, controlled trial comparing a pH neutral, bicarbonate/lactate (B/L)-buffered PD solution to conventional acidic, lactate-buffered solution (C), the overnight dialysate levels of markers of inflammation/wound healing [hyaluronic acid (HA)], mesothelial cell mass/membrane integrity [cancer antigen 125 (CA125)], and fibrosis [transforming growth factor-beta1 (TGF-beta1) and procollagen I peptides (PICP)] were assessed over a six-month treatment period. METHODS: One hundred six patients were randomized (2:1) to either the B/L group or C group. Overnight effluents were collected at entry into the study (time = 0 all patients on control solution) and then at three and six months after randomization. Aliquots were filtered, stored frozen, and assayed for HA, CA125, TGF-beta1, and PICP. Differences between groups were assessed by repeated-measures analysis of variance for unbalanced data using the SAS procedure MIXED. RESULTS: In patients treated with B/L, there was a significant (P = 0.03) increase in CA125 after six months compared with time = 0 (19.76 +/- 11.8 vs. 24.4 +/- 13.8 U/mL; mean +/- SD; N = 51). In the same group of patients, HA levels were significantly decreased at both three and six months in the B/L-treated group (time = 0, 336.0 +/- 195.2; time = 3 months, 250.6 +/- 167.6; and time = 6 months, 290.5 +/- 224.6 ng/mL; mean +/- SD; P = 0.006, N = 47 and P = 0.003, N = 48, respectively). No significant changes in CA125 or HA levels were observed in the control group. There were no significant changes observed in the levels of PICP or TGF-beta1 in the B/L or C group over the six-month treatment period. CONCLUSIONS: These results suggest that continuous therapy with the B/L solutions modulates the levels of putative markers of peritoneal membrane integrity and inflammation. In the long term, this may positively impact the peritoneal membrane, increasing its life as a dialyzing organ.

Acidosis correction with a new 25 mmol/l bicarbonate/15 mmol/l lactate peritoneal dialysis solution.

OBJECTIVE: The aim of this study was to evaluate the effects of a combined 25 mmol/L bicarbonate/15 mmol/L lactate-based solution (Bic/Lac), compared to a 35 mmol/L lactate solution (Lac)--the most commonly used solution for patients in southern Europe--on the venous plasma bicarbonate level in patients treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: This was a randomized, parallel, controlled, open-label study, with patients studied for a period of 3 months preceded by a 1-month baseline and followed by a 1-month follow-up. Patients used the 35 mmol/L lactate solution during baseline and follow-up periods. SETTING: Four Spanish nephrology centers. PATIENTS: Thirty-one (20 Bic/Lac, 11 Lac) well-dialyzed (creatinine clearance > 55 L/week/1.73 m2 body surface area) CAPD patients. INTERVENTIONS: Blood samples were taken for biochemistry tests at all visits. A physical examination was completed at baseline and month 3, and a medical update was completed after 1, 2, and 3 months, and at the follow-up visit. Adverse-event monitoring and notation of prescription changes were carried out continuously. MAIN OUTCOME MEASURE: Effect on venous plasma bicarbonate level. RESULTS: Venous plasma bicarbonate rose by 3.1 mmol/L (confidence intervals 1.6-4.8),from a baseline level of 23.0 mmol/L during the treatment period in those patients treated with Bic/Lac (p < 0.05 vs Lac). The number of acidotic patients (venous plasma bicarbonate < 24 mmol/L) was statistically significantly reduced at every treatment period visit in the Bic/Lac group (p < 0.05). There were no adverse findings with respect to vital signs, physical examination, or clinical symptoms, apart from one death in the control group. CONCLUSIONS: The new Bic/Lac solution allowed better correction of acid-base status than the lactate solution.

In vivo exposure to bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improves ex vivo peritoneal macrophage function.

The impact on peritoneal macrophage (PMO) function of acidic lactate-buffered (Lac-PDF [PD4]; 40 mmol/L of lactate; pH 5.2) and neutral-pH, bicarbonate-buffered (TB; 38 mmol/L of bicarbonate; pH 7. 3) and bicarbonate/lactate-buffered (TBL; 25 mmol/L of bicarbonate/15 mmol/L of lactate; pH 7.3) peritoneal dialysis fluids (PDFs) was compared during a study of continuous therapy with PD4, TB, or TBL. During a run-in phase of 6 weeks when all patients (n = 15) were treated with their regular dialysis regimen with Lac-PDF, median PMO tumor necrosis factor alpha (TNFalpha) release values were 203.6, 89.9, and 115.5 pg TNFalpha/10(6) PMO in the patients subsequently randomized to the PD4, TB, and TBL treatment groups, respectively. Median stimulated TNFalpha values (serum-treated zymosan [STZ], 10 microgram/mL) were 1,894.6, 567.3, and 554.5 pg TNFalpha/10(6) PMO in the same groups, respectively. During the trial phase of 12 weeks, when the three groups of patients (n = 5 per group) were randomized to continuous treatment with PD4, TB, or TBL, median constitutive TNFalpha release values were 204.7, 131.4, and 155.4 pg TNFalpha/10(6) PMO, respectively. Stimulated TNFalpha values (STZ, 10 microgram/mL) were 1,911, 1,832, and 1,378 pg TNFalpha/10(6) PMO in the same groups, respectively. Repeated-measures analysis of variance comparing the run-in phase with the trial phase showed that PMO TNFalpha release was significantly elevated in patients treated with both TB (P = 0.040) and TBL (P = 0.014) but not in patients treated with Lac-PDF (P = 0. 795). These data suggest that patients continuously exposed to bicarbonate- and bicarbonate/lactate-buffered PDFs might have better preserved PMO function and thus improved host defense status.

Bicarbonate/lactate dialysis solution improves in vivo function of peritoneal host defense in rats.

OBJECTIVE: To assess the in vivo peritoneal inflammatory reaction in rats dialyzed with neutral, bicarbonate-lactate-buffered dialysis fluid. METHODS: Chronic peritoneal dialysis was performed for 4 weeks in Wistar rats with two solutions: (1) 40 mmol/L lactate-buffered fluid, pH 5.2, with a glucose concentration of 2.27 g/dL (Lac); and, (2) 15 mmol/L lactate and 25 mmol/L bicarbonate-buffered fluid, pH 7.0-7.5, with a glucose concentration of 2.27 g/dL (Bic-Lac). After 4 weeks, two peritoneal equilibration tests (PET 1 and PET 2) were performed in all animals with each respective solution. PET 1 was done with test solutions alone, whereas, on a subsequent day, PET 2 was performed with test solutions supplemented with endotoxin [lipopolysaccharide (LPS)] to induce peritonitis. RESULTS: During PET 1 no consistent differences were detected in peritoneal permeability between the Lac and Bic-Lac groups. Total dialysate cell count in the Bic-Lac animals was lower than in rats treated with Lac fluid: that is, at 8 hours, the respective counts were 1858+/-524 cells/microL versus 2785+/-1162 cells/microL (p < 0.01). Dialysate from animals dialyzed with Bic-Lac contained more macrophages (at 4 hours: 53.6%+/-35.8% versus 35.8%+/-8.8%, p < 0.001) and fewer neutrophils (at 4 hours: 3.6%+/-1.8% versus 15.4%+/-6.1%, p < 0.001) as compared to those dialyzed with the Lac solution. Concentration of nitrites in 8-hour dwell dialysate samples from Bic-Lac rats was lower than that in the Lac group (0.98+/-0.28 micromol/mL versus 2.32+/-0.87 micromol/mL, p < 0.002), but cytokine levels in the dialysates were comparable. During PET 2, the increase in peritoneal permeability resulting from the LPS-induced inflammatory response was similar for both test solutions. Dialysate cell count was higher in the Lac group versus the Bic-Lac group (at 8 hours: 8789+/-4862 cells/microL versus 3961+/-581 cells/microL, p < 0.001), contained more neutrophils (at 8 hours: 80.0%+/-11.3% versus 54.8%+/-4.4%, p < 0.001) and fewer macrophages (at 8 hours: 6.8%+/-5.6% versus 21.2%+/-3.3%, p < 0.05). During peritonitis, we found a higher overall dialysate concentration of both tumor necrosis factor (TNFalpha: +53%, p < 0.05) and of interferon gamma (IFN-gamma: +303%, p < 0.02), in the Bic-Lac group than in the Lac group. CONCLUSIONS: A lower dialysate cell count, higher percentage of macrophages, and lower percentage of neutrophils in dialysate suggest that Bic-Lac fluid induces a diminished nonspecific inflammatory response of the peritoneal cavity during dialysis. However, after in vivo stimulation, peritoneal cells from animals dialyzed with Bic-Lac solution possess an augmented ability to produce inflammatory cytokines.

A controlled trial of two bicarbonate-containing dialysis fluids for CAPD--final report.

BACKGROUND: The combination of a low pH and a high concentration of lactate which is present in most dialysis fluids is found to be cytotoxic in vitro. For these reasons it would seem logical to use a bicarbonate-containing solution and thus automatically provide a solution with a neutral pH. METHODS: A parallel, randomized, open-label, prospective 2-month trial with an optional 4 month extension was undertaken to compare two novel bicarbonate-based solutions; one containing 38 mmol/l of bicarbonate (B), and one containing a mixture of 25 mmol/l bicarbonate and 15 mmol/l of lactate (B/L), with a control solution (C) containing 40 mmol/l lactate. RESULTS: Three groups of 19 (C), 20 (B), and 20 (B/L) patients were recruited and data from approximately 55 patient months were accumulated in each group. The data show that both bicarbonate-based solutions maintain acid-base levels within the normal range, that there were no changes in any of the other blood biochemistry parameters measured in the peritoneal equilibration test or with regard to adequacy of dialysis, and that furthermore, both solutions were well tolerated. CONCLUSIONS: This study showed that either the bicarbonate or bicarbonate/lactate solutions could be utilized efficaciously in patients undergoing CAPD.

Bicarbonate/lactate- and bicarbonate-buffered peritoneal dialysis fluids improve ex vivo peritoneal macrophage TNFalpha secretion.

Peritoneal macrophage (PMO) function was examined ex vivo after their in vivo exposure to either acidic, lactate-buffered solutions (PD4; 40 mM lactate, pH 5.2), bicarbonate/lactate-buffered solution (TBL; 25 mM/15 mM bicarbonate/lactate, pH 7.3), or bicarbonate-buffered solution (TB; 38 mM bicarbonate, pH 7.3), containing either 1.36 or 3.86% glucose. Initial experiments demonstrated that tumor necrosis factor-alpha (TNFalpha) release (assessed by TNF-direct immunoassay [DIA]) from PMO isolated from the peritoneal cavities of patients exposed to conventional fluid (PD4 1.36% glucose) was lowest after 30 min of intraperitoneal dwell (3591+/-1200 versus 28,946+/-9359 for 240-min dwell [pg/ml], n=5, P < 0.05). Five patients were exposed on 3 successive days to PD4, TBL, and TB for 30-min acute dwells containing 1.36% glucose in the first week and 3.86% glucose during the second. PMO TNFalpha release was assessed after ex vitro exposure to lipopolysaccharide (LPS). Exposure of PMO to TBL or TB (1.36% glucose) resulted in a significant increase in the generation of TNFalpha (pg/2 X 10(6) PMO) compared with PD4. TBL: 68,659+/-35,633, TB: 53,682+/-26,536 versus PD4 17,107+/-8996 (LPS 1.0 ng/ml, n=5 patients, P=0.043 versus PD4 for both). PMO that were recovered from PD4 and TB dwells (3.86% glucose) showed no significant difference in TNFalpha secretion (21,661+/-6934 and 23,923+/-9147, respectively). In contrast, exposure to TBL resulted in a significant increase (41,846+/-11,471) compared with PD4 (LPS 1.0 ng/ml, n=5 patients, P=0.043). These data demonstrate enhanced PMO function after in vivo exposure to bicarbonate- and bicarbonate/lactate-buffered solutions. This response was sustained in TBL alone at the highest glucose concentrations. These results suggest that the newer solutions, and particularly bicarbonate/lactate, might improve host defense status in peritoneal dialysis patients.

Bicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the treatment of infusion pain.

A randomized, double-blind, cross-over study was undertaken to determine the effects of novel bicarbonate (38 mM) and bicarbonate (25 mM)/lactate (15 mM) containing peritoneal dialysis (PD) solutions on infusion pain in patients who experienced inflow pain with conventional lactate (40 mM) solution. Pain was assessed using a verbal rating scale and the validated McGill Pain Questionnaire (MPQ). Eighteen patients were recruited to the study. Both novel solutions resulted in highly statistically significant reductions in inflow pain compared to the control lactate solution, as assessed with both the verbal rating scale and the MPQ. For all pain variables assessed, the bicarbonate/lactate solution was more effective than the bicarbonate solution in alleviating pain. In conclusion, both solutions reduced the infusion pain experienced with control solution, but the bicarbonate/lactate solution appears to be the most effective. In contrast to the most widespread current treatment, which is the manual injection of sodium bicarbonate, the bicarbonate/lactate solution does not have the associated increased risk of peritonitis.

Clinical evaluation of a peritoneal dialysis solution with 33 mmol/L bicarbonate.

OBJECTIVE: To evaluate the efficacy and safety of a new peritoneal dialysis solution with 33 mmol/L bicarbonate. DESIGN: In an acute, prospective, randomized cross-over study, 8 patients were randomized in two groups of 4. On the first study day, the first group performed two consecutive 4-hour exchanges with a dialysis solution containing 35 mmol/L lactate: the first exchange with 13.6 g/L and the second with 38.6 g/L dextrose. On the second study day, the same type of exchanges were performed with bicarbonate. The second group underwent the same treatment, but used bicarbonate solutions on the first day and control solutions on the second study day. Thirty-three patients participated in a 2-month prospective and randomized study. After a 4-week baseline period using solutions containing 40 mmol/L lactate, the patients were dialyzed with either 33 mmol/L bicarbonate solutions or 40 mmol/L lactate solutions. SETTING: Peritoneal dialysis units at the University Hospital of Brescia and the Niguarda Hospital of Milan, Italy. RESULTS: Acute study: Control and bicarbonate solutions had similar effects on blood chemistries and peritoneal transport. Chronic study: Mean venous bicarbonate concentrations remained unchanged in the control group (26.6-27.2 mmol/L), but decreased significantly in the bicarbonate group from 28.8 mmol/L at the start of the study to 23.0 mmol/L after 2 months of bicarbonate administration. Other biochemical parameters remained unchanged. CONCLUSION: A peritoneal dialysis solution with a bicarbonate level of 33 mmol/L does not adequately correct uremic acidosis.

Comparison of in vitro AGE formation between standard PD fluid and a novel bicarbonate/lactate formulation.

Peritoneal advanced glycation end-product (AGE) formation may be accelerated by glucose degradation products produced as a consequence of heat sterilization of peritoneal dialysis (PD) fluid. The formation of these degradation products is reduced if the glucose is separated from the buffers during heat sterilization. This pilot study compared in vitro AGE formation in PD fluid (1.36% and 3.86% glucose) heat sterilized in a two-compartment bag (bicarbonate/lactate buffer) with that in a standard, single-compartment bag (lactate buffer, Dianeal). Peritoneal dialysis fluids were incubated with human serum albumin (HSA, 1 g/L), as a model protein, at 37 degrees C for 0, 5, and 20 days. Formation of AGEs was assessed by measuring fluorescence at each time point. Advanced glycation end-product formation was greater in lactate PD fluid compared with bicarbonate/lactate PD fluid of equivalent glucose strength. Advanced glycation end-product formation in the lactate PD fluid containing 1.36% glucose was comparable to that in the bicarbonate/lactate PD fluid containing 3.86% glucose. The rate of increase in fluorescence per day was greater in the first 5 days of incubation than in the subsequent 15 days. These results are compatible with the presence of greater amounts of glucose-degradation products in the standard single-compartment bag resulting in enhanced AGE formation.

Effect of two-chambered bicarbonate lactate-buffered peritoneal dialysis fluids on peripheral blood mononuclear cell and polymorphonuclear cell function in vitro.

Low pH, high osmolality, increasing glucose concentration, and glucose degradation products (GDP) formed during heat sterilization of conventional peritoneal dialysis (PD) fluids have been shown to have a detrimental effect on cells involved in peritoneal host defense. The two-chambered PD fluid bag in which glucose at pH approximately 3 is separated from a bicarbonate (25 mmol/L)-lactate (15 mmol/L) buffer during heat sterilization permits PD fluids with lower GDP to be delivered to the patient at neutral pH. To establish the possible benefit of two-chambered bag PD fluids on peripheral blood mononuclear cell (PBMC) and polymorphonuclear (PMN) cell function, we compared conventional 1.5% Dianeal (1.5%D) with 1.5% two-chambered bag bicarbonate-lactate (1.5%D-B), and conventional 4.25% Dianeal (4.25%D) with 4.25% two-chambered bag bicarbonate-lactate (4.25%D-B). Furthermore, to study the effect of the sterilization process on PBMC and PMN function, we compared filter-sterilized 4.25%D (4.25%D-F) with 4.25%D and 4.25%D-B. PBMC were harvested by Ficoll-Hypaque separation, and 2.5 x 10(6) cells in RPMI were incubated with an equal volume of the test fluids for 4 hours, pelleted, and resuspended in RPMI containing 10 ng endotoxin for a further 20 hours. Tumor necrosis factor alpha (TNF-alpha) production by endotoxin-stimulated PBMC was not significantly different (P = 0.10) between 1.5%D-B and 1.5%D, but was significantly higher (P = 0.01) with 4.25%D-B compared with 4.25%D. PBMC exposed to filter-sterilized fluid (4.25%D-F) showed significantly higher endotoxin-stimulated TNF-alpha production compared with 4.25%D (P = 0.02), but was not significantly different from 4.25%D-B (P = 0.40). PMN were harvested by Ficoll-Hypaque separation and 10 x 10(6) cells incubated with test fluids for 30 minutes. After incubation, phagocytosis (phagocytosis index) was determined by the uptake of 14C-labeled Staphylococcus aureus, oxidative burst by reduction of ferricytochrome C to ferrocytochrome C on stimulation with PMA, and enzyme release by measurement of endotoxin-stimulated bactericidal/permeability increasing protein (BPI). Bicarbonate-lactate two-chambered fluids of similar osmolality and glucose concentration conferred a significant improvement in phagocytosis (P = 0.02 for 1.5%D-B and P < 0.001 for 4.25%D-B). Oxidative burst and BPI release were significantly higher in 4.25%D-B compared with 4.25%D (P < 0.001). Filter-sterilized 4.25%D-F conferred a significant improvement in phagocytosis and oxidative burst compared with 4.25%D (P < 0.001) or 4.25%D-B (P < 0.001). Furthermore, conventional 4.25%D was associated with significantly lower BPI release compared with 4.25%D-F (P = 0.01). GDP's acetaldehyde and 5-HMF were analyzed in 4.25%D-B, 4.25%D, and 4.25%D-F. Acetaldehyde was below the lower limit (0.79 ppm) of the standard curve in 4.25%D-B and 4.25%D-F fluids but was detected (3.76 to 5.12 ppm) in all of the 4.25%D fluids. Relative levels of 5-HMF in the 4.25%D-B (0.032 to 0.041 Abs @ 284 nm) and 4.25%D (0.031 to 0.036 Abs @ 284 nm) were similar. The lowest levels (0.001 Abs @ 284 nm) were observed in the filter-sterilized 4.25%D-F. The beneficial effects of two-chambered bicarbonate lactate-buffered PD fluids on PBMC and PMN function are probably related to reduction of GDP from heat sterilization of glucose in a separate chamber at a lower pH. This improvement in biocompatibility could have a beneficial affect on peritoneal defenses.

Reduced glucose degradation products in bicarbonate/lactate-buffered peritoneal dialysis solutions produced in two-chambered bags.

OBJECTIVES: The aims of the current study were: (1) to determine the effects of peritoneal dialysis (PD) solutions at different glucose concentrations on the growth of cultured cells; (2) to determine whether a bicarbonate/lactate-based solution, as a result of the configuration of its components during heat sterilization in a two-chambered bag, was lower in glucose degradation products than a corresponding lactate-based PD solution; and (3) to determine whether lower glucose degradation corresponded to a decreased inhibition of cell growth. DESIGN: Growth inhibition of cells exposed to lactate-based PD solutions at three different glucose concentrations was determined. Bicarbonate/lactate-based and lactate-based solutions at high glucose concentration (3.86%) were further analyzed for presence of glucose degradation products and inhibition of cell growth. METHODS: Cell growth was determined by neutral red uptake, measured by optical density at 540 nm. Glucose degradation to acetaldehyde or fructose was determined by gas chromatography-mass spectroscopy and high-performance liquid chromatography. RESULTS: Only 3.86% glucose lactate-based PD solution caused significant inhibition of cell growth (p < 0.05). The heat-sterilized, bicarbonate/dlactate-based solution (3.86% glucose) had lower levels of fructose and acetaldehyde than a conventional heat-sterilized, lactate-based solution with the same glucose concentration. Growth of cultured cells exposed to the bicarbonate/lactate-based solution was significantly improved (p < 0.05) over growth in the conventional solution. CONCLUSIONS: The bicarbonate/lactate-based solutions, manufactured and heat-sterilized in two-chambered bags, were lower in glucose degradation products than that corresponding lactate-based PD solutions, and demonstrated improved in vitro biocompatibility as measured by the growth of cultured cells.

A randomized controlled trial of a bicarbonate- and a bicarbonate/lactate-containing dialysis solution in CAPD.

OBJECTIVE: To evaluate the safety and efficacy of bicarbonate- and bicarbonate/lactate-based PD fluids. DESIGN: A randomly allocated prospective controlled trial lasting eight weeks. SETTING: Five renal units in Europe. PATIENTS: Individuals who have been treated by CAPD for at least three months and who have had at least one month's therapy with 40 mmol/L lactate PD fluid. Those with recent infection, diabetes or other serious illness are excluded. Forty-seven individuals have entered the study so far. INTERVENTIONS: Patients are randomly allocated to three groups. Group 1 receive 40 mmol/L lactate dialysate, Group 2 are given 38 mmol/L bicarbonate fluid and Group 3 are tested with a 25 mmol/L bicarbonate and 15 mmol/L lactate dialysate. OUTCOME MEASURES: The primary outcome measure is the plasma bicarbonate level. Adverse events and ease of use of the two-chambered bags used by Groups 2 and 3 are also being assessed. RESULTS: To date, plasma bicarbonate levels have been the same in all treatment groups up to the end of the trial period. There are no differences in serum lactate levels. No side effects are attributable to the test fluids. The patients have managed the two-chambered bags successfully. CONCLUSION: This trial is still ongoing, but to date, neutral bicarbonate based fluids have been as effective as lactate dialysate in treating uremic acidosis.

Effect of bicarbonate-based dialysis solutions on intracellular pH (pHi) and TNFalpha production by peritoneal macrophages.

OBJECTIVE: To compare the effect of Dianeal and two newly-formulated bicarbonate-based peritoneal solutions on intracellular pH (pHi), tumor necrosis factor-alpha (TNFalpha) mRNA level, and TNFalpha secretion by peritoneal macrophages (PMphi). DESIGN AND MEASUREMENTS: Peritoneal macrophages were isolated from dialysates collected after overnight dwells in peritonitis-free continuous ambulatory peritoneal dialysis patients. Dialysis solutions contained 1.5% or 4.25% dextrose. HCO3 concentrations of bicarbonate-(TB) and bicarbonate/lactate-buffered (TBL) solution were 38 mM and 25 mM, respectively. TBL also contained lactate at a concentration of 15 mM. pCO2 levels were 78 mmHg and 51 mmHg, respectively. In all experiments pCO2 was carefully maintained at a stable level. The pHi was measured by spectrofluorometry in BCECF-loaded PMphi exposed to different dialysis solutions or Hank's balanced salt solution. TNFalpha levels were measured by ELISA in the supernatant of lipopolysaccharide- (LPS) stimulated PMphi after their incubation in different solutions for 15 and 30 minutes. TNFalpha mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR) of total RNA extracted from LPS-stimulated PMphi after their incubation in different solutions for 30 minutes. beta-actin mRNA was used as the control. RESULTS: Dianeal caused a profound drop in pHi to below 6.2. Following an initial drop, pHi stabilized after 4 minutes at levels of 6.96 and 6.8 after incubation in TB and TBL, respectively. In comparison to the control solution, a fall of 11% and 21% in TNFalpha secretion was seen after incubation in TB for 15 and 30 minutes, respectively, and 15% and 26% after incubation in TBL. Under identical conditions, Dianeal (Baxter, McGaw Park, IL, U.S.A.) caused 59% and >95% suppression of TNFalpha secretion. Accordingly, TNFalpha mRNA level in PMphi was severely depressed by Dianeal but no detectable inhibition was observed following incubation for 30 minutes in TB and TBL. When dextrose concentration in TB and TBL was increased from 1.5% to 4.25%, TNFalpha secretion by PMphi was not suppressed by more than 49%, even after 30 minutes incubation. Moreover, suppression of TNFalpha mRNA levels could not be detected with TB or TBL even at high dextrose concentrations. CONCLUSIONS: In contrast to Dianeal, both bicarbonate-based solutions caused only a mild drop in pHi of PMphi. We postulate this effect to be responsible for the improved capacity of PMphi to secrete TNFalpha when incubated in bicarbonate-based solutions compared to Dianeal. Reflecting its known cytotoxicity, dextrose in high concentrations diminishes the protective effect of TB and TBL on immune function of PMphi. TBL is as effective as TB in preventing the deleterious effect of Dianeal on PMphi function.

In vitro effects of bicarbonate and bicarbonate-lactate buffered peritoneal dialysis solutions on mesothelial and neutrophil function.

The inclusion of bicarbonate in the formulation of peritoneal dialysis solutions may avoid the in vitro impairment of certain cell functions seen with acidic lactate-based fluids. The supranormal physiological levels of HCO3- and PCO2 inherent in such formulations may, however, not be biocompatible. This study compared the in vitro biocompatibility of a pH 5.2 lactate-based formulation with formulations containing either 40 mM lactate at pH 7.4, 38 mM HCO3- at pH 6.8 (PCO2 at approximately 240 mm Hg) or 7.4 (PCO2 at approximately 60 mm Hg), and 25 mM HCO3- plus 15 mM lactate at pH 6.8 (PCO2 at approximately 160 mm Hg) or 7.4 (PCO2 at approximately 40 mm Hg). Significant release of lactate dehydrogenase or decreases in ATP content by human peritoneal mesothelial cells (HPMC) and human peripheral polymorphonuclear leukocytes (PMN) after a 30-min exposure to each test solution was only seen with the pH 5.2 lactate-based fluid. The ATP content of HPMC exposed to this fluid returned to control levels after 30 min of recovery in M199 control medium but showed a trend toward decreasing ATP content at 240 min. Similarly, interleukin (IL)-1 beta-induced IL-6 synthesis by HPMC was also only significantly reduced by the pH 5.2 lactate solution. PMN chemiluminescence was unaffected by 30-min exposure to all test solutions except for the pH 5.2 lactate formulation. Staphylococcus epidermidis phagocytosis was reduced to between 46 to 57% of control with all test solutions except the pH 5.2 lactate solution, which further suppressed the chemiluminescence response to 17% of control. These data suggest that short exposure to supranormal physiological levels of HCO3- and PCO2 does not impair HPMC or PMN viability and function. Furthermore, neutral pH lactate-containing solutions show equivalent biocompatibility to bicarbonate-based ones.

Clinical evaluation of an optimized 1.1% amino-acid solution for peritoneal dialysis.

A significant percentage of dialysed patients have inadequate protein intake. One strategy for treating the protein malnutrition in peritoneal dialysis patients is to replace glucose in the dialysis solution by amino acids. A new peritoneal dialysis solution containing 1.1% amino acids in a formulation optimized for renal patients and with a lactate concentration of 40 mmol/l has been evaluated. Fifteen CAPD patients completed a non-randomized prospective 3-month study. Each patient received 2 litres of the optimised 1.1% amino acid solution for the second exchange of the day with a dwell time of 5-6 h. Indicators of efficacy were serum albumin and transferrin. After 3 months of intraperitoneal amino acids, serum albumin levels significantly increased from 32.7 +/- 2.3 to 35.1 +/- 2.2 g/l (mean +/- SD; P < 0.01). This occurred in parallel with a significant increase in transferrin levels from 2.21 +/- 0.26 to 2.39 +/- 0.27 g/l (P < 0.05). As expected, urea rose from 23.7 +/- 6.8 to 29.9 +/- 9.4 mmol/l. Interestingly bicarbonate did not change (25.5 +/- 4.2 versus 25.2 +/- 3.3 mmol/l). These results suggest that the optimized formulation is effective in improving nutritional parameters in CAPD patients while avoiding unwanted side-effects such as acidosis.

Evaluation of short-chain polypeptides as an osmotic agent in continuous ambulatory peritoneal dialysis patients.

OBJECTIVES: To assess whether dialysate containing short-chain polypeptides is well tolerated in continuous ambulatory peritoneal dialysis (CAPD) patients and to determine its effect on fluid and solute transport, plasma amino acid levels, and biochemical parameters. DESIGN: Two-treatment, two-period cross-over design. SETTING: Renal Unit, Academic Medical Center, Amsterdam and Renal Unit, University Hospital, Gent. PATIENTS: Two groups of 10 stable CAPD patients. INTERVENTION: All patients received a trial solution (1.36% glucose and 1% peptides, 381 mOsm/kg) and a control solution (2.27% glucose, 404 mOsm/kg) in randomized order. The patients were examined on four consecutive days in which two dwell periods on days 1 and 3 of either 4 (Group I) or 8 hours (Group II) were performed. RESULTS: The peptide solution was well tolerated in all patients. In addition, no differences were found in the parameters for the effective peritoneal surface area and the intrinsic permeability, implying that no irritating effect of the peptide solution was present. Net ultrafiltration was not different in Group I: -43 +/- 125 versus 86 +/- 125 mL (mean +/- SEM) and marginally lower in Group II: -94 +/- 64 versus 51 +/- 64 mL, despite the lower osmolality of the trial solution compared to the control solution. Glucose absorption was higher than the peptide absorption in all patients: Group I: 66 +/- 10% versus 57 +/- 13% (p = 0.0003); Group II: 80 +/- 5% versus 72 +/- 11% (p = 0.006). No differences in plasma amino acid profiles could be detected. CONCLUSIONS: Short-chain polypeptides are absorbed less than glucose and can be used as an osmotic agent in CAPD patients. However, longer-term studies are needed to evaluate possible additional effects of peptides on the nutritional status of CAPD patients.