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J Passlick-Deetjen

Publications and source records attributed to J Passlick-Deetjen.

At least 19 recordsLinked to original sources
PubMed2006

Effects of an increase in time vs. frequency on cardiovascular parameters in chronic hemodialysis patients.

UNLABELLED: Cardiovascular mortality is still high and many risk factors are inadequately controlled in patients on conventional chronic hemodialysis. Recent studies on intensified treatment schedules by either increasing length or frequency of dialysis sessions have shown promising results with better control of blood pressure, reduction of left ventricular hypertrophy and easier control of calcium/phosphate metabolism. AIM: The present observational study compared the effect of different forms of "intensified dialysis treatment" i.e. either long nightly intermittent (LNHD, 3 x 7.5 - 8 h) or short daily dialysis sessions (DHD, 6 x 2.5 - 3 h) on cardiovascular parameters, phosphate and anemia control in comparison to standard treatment schedules (SHD, 3 x 4 - 5 h). METHODS: All patients stable on hemodialysis between 18 and 80 years of age and with either uncontrolled hypertension and/or left ventricular hypertrophy and/or frequent intradialytic hypotension, were asked to participate in intensified dialysis therapy by either LNHD or DHD. Patients not willing to change their dialysis regime were asked to participate as control group (SHD). Primary end point was 24-h ambulatory blood pressure, secondary end points were predialysis blood pressure, left ventricular mass index (LVMI) and fractional shortening (FS), control of calcium, phosphate and anemia. Patients were followed up for 1 year. RESULTS: 17 patients opted for LNHD, 8 for DHD, 19 patients served as control group. After 1 year of treatment 24-h blood pressure was unchanged in all groups. Predialysis systolic blood pressure decreased in LNHD and DHD, but increased in SHD. Mean LVMI decreased in all treatment groups (DHD -20.1 +/- 24.0%, SHD -13.6 +/- 33.4%, LNHD -6.1 +/- 32.2%). The mean number of antihypertensive tablets/day was reduced in DHD by 3.3 tablet units, in LNHD by 1.2 tablet units, but increased in SHD patients. FS improved in patients on LNHD and DHD, but decreased in patients on SHD. Regression of LVMI was independent of dry weight which was unchanged in LNHD and SHD but increased in DHD. In contrast to SHD, phosphate control and Ca x P product improved in DHD and LNHD with less phosphate binding tablets. Intact PTH did not change in SHD, but decreased in DHD and LNHD. Hemoglobin increased in groups on intensified treatments, but fell in SHD. EPO resistance index fell in LNHD, but increased in DHD and SHD. CONCLUSION: While reduction in 24-h blood pressure was not achieved by intensified dialysis, both schedules showed favourable effects on LVMI and FS with less antihypertensive medication. This was independent of reduction in dry weight. These effects were more pronounced in DHD patients. In contrast, in SHD patients, stable 24-h blood pressure and reduction in LVMI were achieved on the expense of an increasing amount of antihypertensive medication and with worsening of FS.

Adolescent↗
PubMed2004

Influence of hemodialysis membrane permeability on serum levels of advanced glycation end products (AGEs) and homocysteine metabolites.

BACKGROUND: [corrected] Advanced glycation end products (AGEs), total homocysteine (tHcy) and the homocysteine metabolites cystathionine (Cysta) and dimethylglycine (DMG) are increased in serum of patients with end-stage renal disease. The aim of this prospective randomized study was to compare the efficacy of polysulfone high-flux vs. polysulfone low-flux hemodialysis (HD) treatment regarding removal of AGEs, tHcy, Cysta and DMG. PATIENTS AND METHODS: Twenty-nine patients on chronic HD treatment were randomly assigned to 2 groups in a 3-period 2-treatment design with low flux (A)--high flux (B)--low flux (A) for group I and B-A-B for group II, 6 weeks each period. The following parameters were measured in pre- and postdialytic serum samples at baseline and the end of each period: total serum fluorescence, Nepsilon-carboxymethyllysine (CML), free and protein-bound pentosidine, tHcy, Cysta and DMG. RESULTS: There was increased removal of free pentosidine during high-flux HD treatment compared to low-flux HD treatment, attaining significance between the second and third treatment periods (group 1: 86.0 +/- 4.7% vs. 79.2 +/- 8.8%, p = 0.007; group II: 84.0 +/- 6.3% vs. 79.8 +/- 9.8%, p = 0.049 for high vs. low flux). The intradialytic reduction rates for total serum fluorescence, tHcy, Cysta, DMG did not differ between high- and low-flux HD treatment. Protein-bound pentosidine and CML did not decrease during the dialysis sessions, neither with high-flux nor with low-flux HD membrane. Despite a strong decrease during single HD session, the predialytic levels of free pentosidine, tHcy, Cysta and DMG remained unchanged during the study period both for high- and low-flux HD treatment. CONCLUSION: The more pronounced effect of high-flux dialysis on the removal rate of free pentosidine, found in this randomized crossover study, could not translate into a significant difference in predialysis levels after a 6-week treatment period. We could not find any differences between polysulfone high- and low-flux membranes for lowering predialytic serum concentrations of the measured AGEs, which are mainly bound on albumin.

Arginine↗
PubMed2002

One-compartment model for amino acids and other biological molecules in peritoneal dialysis.

OBJECTIVES: Investigation of the main factors determining the concentration-time course of amino acids and biological molecules in serum and dialysates. METHODS: In a randomized, 3-period crossover study, 11 patients were treated once with each of 3 peritoneal dialysis solutions, 1 containing amino acids and bicarbonate, 1 containing glucose and bicarbonate and 1 containing glucose and lactate. Nineteen amino acids, 3 proteins, 2 metabolites and 2 ions were measured in serum and dialysate. A standard compartment model was fitted to the data. RESULTS: The amino acids differed significantly in their kinetic characteristics (p < 0.001), mainly volume of distribution and elimination rate. Differences in absorption were small compared to the interpatient variation. The average transport rate from serum to dialysate was 0.50-1.14 h(-1), from dialysate to serum 0.33-0.41 h(-1), for elimination from the central compartment 0.35 to 2.27 h(-1), for volume of distribution 0.29 to 0.83 l/kg, for serum protein binding 19-47%, for amount in tissue 82 - 95%, for endogenous metabolic rate 16-151 micromol x kg(-1) x h(-1). The volume of distribution correlated with the R group (polar positive < aliphatic < polar uncharged). For the various proteins, the 2 bicarbonate solutions had higher serum-to-dialysate transport rates than the lactate solution (p = 0.018-0.601). CONCLUSION: The compartment model demonstrated its usefulness. Accordance with literature data for healthy volunteers indicated the validity of the estimates.

Adult↗
PubMed2001

In vitro formation of N(epsilon)-(carboxymethyl)lysine and imidazolones under conditions similar to continuous ambulatory peritoneal dialysis.

Conventional peritoneal dialysis fluids (PDFs) lead to formation of advanced glycation end-products (AGE) in the peritoneal membrane. In this study, we investigated in vitro the dependence of AGE formation on regular changes of PDFs, as performed during continuous ambulatory peritoneal dialysis (CAPD), and on the contribution of high glucose concentration versus glucose degradation products (GDPs). Under conditions similar to CAPD, protein glycating activity of a conventional single chamber bag PDF (CAPD 4.25%), two double chamber bag PDFs (CAPD Balance 4.25% and CAPD Bicarbonate 4.25%) and a sterile filtered control was measured in vitro by N(epsilon)-(carboxymethyl)lysine (CML) and imidazolones, two well characterized, physiologically relevant AGE structures. Regular changes of PDFs increased AGE formation (CML 3.3-fold and imidazolone 2.6-fold) compared to incubation without changes. AGE formation by CAPD 4.25% was increased compared to control (imidazolones 7.9-fold and CML 3.3-fold) and the use of double chamber bag PDFs led to a decrease of imidazolones by 79% (CAPD Bicarbonate 4.25%) and by 66% (CAPD Balance 4.25%) and to CML contents similar to the control. These results indicate that a major part of AGEs were formed by GDPs in PDFs, whereas only a minor part was due to high glucose concentration. The use of double chamber bag fluids can reduce AGE formation considerably.

Dialysis Solutions↗
PubMed2001

Influence of neutral-pH dialysis solutions on the peritoneal membrane: a long-term investigation in rats.

OBJECTIVE: Glucose degradation products (GDPs) and low pH are potential causes of bioincompatibility of peritoneal dialysis fluids (PDFs). The aim of the present study was to compare the effect of 6 weeks' exposure of the peritoneum in rats to two different PDFs: a standard PDF with a low pH and high level of GDPs (CAPD 3: Fresenius Medical Care, Bad Homburg, Germany), and a modified PDF with a low level of GDPs and a physiologic pH (CAPD 3 Balance: Fresenius Medical Care). METHODS: After catheter implantation, rats were exposed twice daily for 6 weeks to CAPD 3 fluid or to CAPD 3 Balance. At the beginning and at the end of the study, a 4-hour dwell was performed in every rat to evaluate intraperitoneal inflammation and its effect on total collagen synthesis in the in vitro cultured rat mesothelial cells (ex vivo study). Additionally, after 6 weeks' exposure, the peritoneal cavity was opened, and macroscopic changes were evaluated according to a semiquantitative scale. Peritoneal samples were also taken for morphology study. RESULTS: In rats treated with CAPD 3 fluid, intraperitoneal inflammation was comparable at the beginning and at the end of the experiment. In animals exposed to CAPD 3 Balance, the intensity of the intraperitoneal inflammation decreased during the study (cell count, p = 0.0781; neutrophil:macrophage ratio, p < 0.01; nitrite concentration, p < 0.05; hyaluronan level, p < 0.05). The capacity of effluent dialysate from CAPD 3 rats to activate collagen synthesis in in vitro-cultured mesothelial cells was the same at the beginning and at the end of the study. In the CAPD 3 Balance group, this capacity was statistically significantly lower at the end of the study than at the beginning (p < 0.05). The mean thickness of the visceral peritoneum was comparable in both groups of animals, but, macroscopically, more severe fibrosis was found in the peritoneum of rats exposed to CAPD 3 as compared with animals treated with CAPD 3 Balance (p < 0.05). CONCLUSION: We showed that, in the rat model of peritoneal dialysis, chronic exposure of the peritoneum to PDFs with low GDPs and a physiologic pH diminished the intraperitoneal inflammatory reaction induced by dialysis, and reduced peritoneal fibrosis.

Animals↗
PubMed2001

High glucose dialysis solutions increase synthesis of vascular endothelial growth factors by peritoneal vascular endothelial cells.

OBJECTIVE: Increased peritoneal vasculature has been reported in long-term peritoneal dialysis (PD), and vascular endothelial growth factors (VEGFs) have been found in dialysate. High concentrations of glucose or lactate, glucose degradation products (GDPs), and low pH of dialysis solutions are all possible factors in increased peritoneal VEGF synthesis. In this study, we investigated the effects of high glucose dialysis solutions on VEGF synthesis by peritoneal vascular endothelial cells (PVECs). METHODS: The PVECs were isolated from rat omentum and were incubated for 4 hours in three different culture media [M199 media (control), conventional dialysis solutions containing 4.25% glucose diluted with an equal volume of M199 media (HGD), and M199 media containing 118 mmol/L mannitol as an osmolar control (mannitol)]. Levels of VEGF protein in the culture supernatant were measured by ELISA, and mRNA expression was determined by Northern blot analysis. Data are presented as percent of control. RESULTS: After incubation for 4 hours, the number of cells did not differ between the 3 groups. Levels of VEGF in culture supernatant were significantly higher in the HGD group (124% +/- 19%, p = 0.006) as compared with the control and mannitol (85% +/- 10%) groups. The mRNA expression of VEGF appeared to be higher in the HGD group (128% +/- 49%) than in the control and mannitol (94% +/- 18%) groups. CONCLUSION: High glucose dialysis solutions increased VEGF synthesis by PVECs. The relationship between VEGF synthesis by PVECs and neovascularization of the peritoneum observed in long-term peritoneal dialysis patients has to be studied further.

Animals↗
PubMed2000

First in vitro and in vivo experiences with Stay-Safe Balance, a pH-neutral solution in a dual-chambered bag.

In addition to low pH and high osmolarity, glucose degradation products (GDPs) are considered to play a major role in the bioincompatibility of peritoneal dialysis fluids (PDFs). The formation of GDPs can be reduced by separating the glucose component of the solution (kept at very low pH) from the lactate component of the solution (kept at alkaline pH) during sterilization and storage. This development has been achieved by the use of a dual-chambered bag. Immediately before infusion, the seam between the two chambers is opened, and the contents are mixed. The result is a fluid with a more physiologic pH in the range 6.8 - 7.4. Concentrations of 3-deoxyglucosone (3-DG), methylglyoxal (MG), acetaldehyde (AA), and formaldehyde (FA) in Stay-Safe Balance (Fresenius Medical Care, Bad Homburg, Germany) were remarkably reduced when compared to conventional PD solution [conventional PDF (1.5% glucose): 172 micromol/L, 6 microLmol/L, 152 micromol/L, and 7 micromol/L respectively; Stay-Safe Balance (1.5% glucose): 42 micromolL, < 1 micromol/L, < 2 micromol/L, and < 3 micromol/L respectively; conventional PDF (4.25% glucose): 324 micromol/L, 10 micromol/L, 182 micromol/L, and 13 micromol/L respectively; Stay-Safe Balance (4.25% glucose): 60 micromol/L, < 1 micromol/L, < 2 micromol/L, and < 3 micromol/L respectively). Human peritoneal mesothelial cells (HPMCs) were exposed to a control solution, a conventional PDF [CAPD 2, 1.5% glucose (Fresenius Medical Care, Bad Homburg, Germany)], and Stay-Safe Balance, either in a co-incubation model (24-hour PDF exposure) or in a pre-incubation model (30-min PDF exposure), followed by 24-hour recovery in culture medium. Interleukin-1beta (IL-1beta)-stimulated (1 ng/mL) IL-6 secretion from HPMCs was assessed by ELISA. Exposure of HPMCs to conventional PDF resulted in a significant reduction in IL-6 release, which was fully restored following exposure to Stay-Safe Balance. In addition to the short-term investigations, long-term in vitro studies were also carried out. All fluids had near-neutral pH and were changed every second day. After 1, 3, 5, 7, 10, and 13 days of exposure, cell viability was assessed. Whereas exposure to conventional PDF resulted in a significant reduction in HPMC viability after just 3 - 5 days, no significant toxicity of filter-sterilized or dual-chambered fluid was observed for up to 13 days. An observational study with 9 patients suggested that the efficacy of Stay-Safe Balance is equivalent to that of conventional solution. However, even short-term treatment (8+/-1 weeks) with this more biocompatible solution seems to improve mesothelial cell mass as indicated by a rise in cancer antigen 125 (CA125) from a baseline of 47+/-37 U/min to 172+/-90 U/min. Our data indicate that Stay-Safe Balance may help to better preserve peritoneal membrane cell function. An ongoing European multicenter study is expected to confirm these results.

Cells, Cultured↗
PubMed1999

The use of different buffers during continuous hemofiltration in critically ill patients with acute renal failure.

OBJECTIVE: To determine the impact of different hemofiltration (HF) replacement fluids on the acid-base status and cardiovascular hemodynamics in patients with acute renal failure (ARF) and continuous veno-venous hemofiltration (CVVH). DESIGN: Prospective, cohort study. SETTING: Intensive Care Unit of the Heinrich Heine University Hospital, Düsseldorf, Germany. SUBJECT AND METHODS: One hundred and thirty-two critically ill patients with acute renal failure and continuous veno-venous HF were studied. Fifty-two patients were subjected to lactate-based (group 1), and 32 to acetate-based hemofiltration (group 2) while 48 (group 3) were treated with bicarbonate-based buffer hemofiltration fluid. Fifty-seven had a septic, and 75 a cardiovascular, origin of the ARF. Creatinine, blood urea nitrogen (BUN), serum bicarbonate, arterial pH, lactate and Apache II scores were noted daily. MAIN RESULTS: The mean CVVH duration was 9.8 +/- 8.1 days, mortality was 65%. No difference was present between the groups under investigation with regard to the main clinical parameters. Lactate- and bicarbonate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Serum bicarbonate values at 48 h after the initiation of CVVH treatment were 25.7 +/- 3.8 mmol/l (p < 0.001) in group 1, 20.6 +/- 3.1 mmol/l in group 2 and 23.3 +/- 3.9 mmol/l (p < 0.001) in group 3. While a lack of increase in serum bicarbonate and arterial pH was correlated to poor prognosis in lactate- and bicarbonate-based hemofiltration, no such observation was made in acetate-based hemofiltration. Cardiovascular hemodynamics were superior in patients treated with lactate- and bicarbonate-based buffer solution as compared to those treated with acetate-based buffer solution. CONCLUSIONS: The degree of correction of acidosis during hemofiltration was determined by patient outcome in patients treated with lactate- and bicarbonate-based buffer solutions, but not in patients receiving acetate-buffered solution. Bicarbonate and lactate-based buffer solutions were found to be superior to acetate-based replacement fluid.

APACHE↗
PubMed1998

Randomized long-term evaluation of bicarbonate-buffered CAPD solution.

BACKGROUND: Over the past 15 years, lactate has been used successfully as a buffer in peritoneal dialysis solutions, although its effectiveness in the correction of uremic acidosis and its biocompatibility on peritoneal resident cells have been questioned. In addition, some investigators have suggested other potential adverse metabolic effects resulting from the unphysiologically high lactate flux into the body during CAPD. These potential problems associated with lactate-containing CAPD solution prompted the search for alternative buffer-containing solutions. Bicarbonate, the physiological buffer, was considered when the problem of calcium and magnesium carbonate solubility was solved by the use of a two-compartment bag system, allowing the mixing of bicarbonate and divalent cations immediately before infusion. The long-term tolerance, safety, efficacy and therapeutic value of a bicarbonate-buffered peritoneal dialysis solution were evaluated in this study. METHODS: This open, randomized, controlled, multicenter study comparing a 34 mmol/liter bicarbonate- with a 35 mmol/liter lactate-buffered peritoneal dialysis solution was performed in two consecutive 12-week-treatment phases. Fourteen Centers participated in this trial. RESULTS: A total of 69 out of initially 123 randomized patients completed the six-month study period (36 patients in the bicarbonate group and 33 in the lactate group). While the arterial acid base status of the total study population did not change during the study period and no significant difference was observed between the two treatment groups, the acid-base status of patients in the bicarbonate group entering the study with a metabolic acidosis significantly improved (mean +/- SD; blood pH: baseline = 7.361 +/- 0.05, week 12 = 7.380 +/- 0.04, P < 0.05; week 24 = 7.388 +/- 0.03 P < 0.05; plasma bicarbonate: baseline = 19.49 +/- 3.01 mmol/liter, week 12 = 21.16 +/- 2.63 mmol/liter, P < 0.01; week 24 = 21.51 +/- 2.42 mmol/liter, P < 0.01). No significant changes were recorded in acidotic patients treated with the conventional lactate-buffered solution. The changes in plasma bicarbonate from baseline during the study was significantly different between the groups (week 12: lactate = +0.11 +/- 2.21 mmol/liter, bicarbonate = +1.69 +/- 2.55 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.21 to 2.94 mmol/liter; week 24: lactate = +0.03 +/- 2.48 mmol/liter, bicarbonate = +1.82 +/- 2. 96 mmol/liter, P < 0.05, 95% confidence interval for the difference 0.16 to 3.42 mmol/liter). The normalized protein catabolic rate (nPCR) slightly but significantly decreased in the lactate group (baseline -0.90 +/- 0.23 g/kg/day, week 24 -0.83 +/- 0.21 g/kg/day, P < 0.01) and increased in the bicarbonate group (baseline +0.89 +/- 0.28 g/kg/day, week 24 +0.92 +/- 0.26 g/kg/day, P < 0.05). Changes from baseline between groups were significant (week 24, lactate = -0. 099 +/- 0.15 g/kg/day, bicarbonate = 0.049 +/- 0.12 g/kg/day, P < 0. 01, 95% confidence interval for the difference 0.068 to 0.229 g/kg/day). Other evaluated parameters (biochemical profile, peritoneal function parameters, dialysate protein loss) did not differ significantly between the two groups. No adverse effects related to the study solution were recorded. CONCLUSIONS: These results support the efficacy and safety of bicarbonate-buffered peritoneal solutions in a controlled randomized comparison for up to six months. Peritoneal dialysis solutions containing the physiological buffer bicarbonate might effectively replace conventional lactate-buffered CAPD solutions.

Acid-Base Equilibrium↗
PubMed1998

Biocompatibility and buffers: effect of bicarbonate-buffered peritoneal dialysis fluids on peritoneal cell function.

BACKGROUND: Conventional peritoneal dialysis fluids (PDF) have been shown to compromise the function of both leukocytes and human peritoneal mesothelial cells (HPMC). Various in vitro studies have identified the low initial pH in combination with high lactate content, as well as the hyperosmolality and high glucose concentration present in currently used solutions as the primary determinants of their bioincompatibility. Bicarbonate buffered PDF (at neutral pH) display improved in vitro biocompatibility as compared to conventional, lactate buffered PDF. However, little information is currently available regarding the potential impact of PDF on the function of human peritoneal fibroblasts (HPFB), the major cell population present in peritoneal interstitium. METHODS: The current study compares the effect of bicarbonate and lactate buffered PDF in a model system of resting peritoneal mesothelial cells and fibroblasts cultured from human omentum. Interleukin-1 beta-stimulated IL-6 release from HPMC and HPFB was used as the cell functional parameter. RESULTS: While short (30 min) pre-exposure to lactate buffered PDF significantly reduced the IL-1 beta-stimulated IL-6 release from HPMC during a subsequent recovery period (24 hr), a significant decrease in HPMC IL-6 secretion with bicarbonate buffered PDF was only observed after prolonged (> or = 60 min) exposure. In contrast, no significant IL-6 inhibition was detected with HPFB pre-exposed to PDF for up to 90 minutes. A significant suppression of HPFB IL-6 secretion was only observed in coincubation experiments (24 hr) with dilutions of both types of PDF. CONCLUSIONS: These results indicate that (i) bicarbonate buffered PDF are less inhibitory to peritoneal cell function as compared to conventional, lactate buffered PDF; and (ii) HPFB may be more resistant than HPMC to bioincompatible PDF.

Bicarbonates↗
PubMed1997

In vitro effects of glucose polymer-containing peritoneal dialysis fluids on phagocytic activity.

Commercially available peritoneal dialysis fluids (PDFs) are known to impair peritoneal cellular defense mechanisms. We have investigated the influence of glucose polymer-containing PDFs on phagocytic function in vitro. Polymorphonuclear neutrophils (PMNLs) and monocytes (MNs) from 10 continuous ambulatory peritoneal dialysis patients and 10 healthy donors were incubated in PDFs containing either 7.5% icodextrin (glucose polymer) or 1.5% glucose at original pH and pH 7.4. Chemiluminescence response and H202 production were measured following stimulation with preopsonized Staphylococcus epidermidis or phorbol myristate acetate. Phagocytosis of radiolabeled bacteria and killing capacity of the cells were determined. A comparison of the impact of glucose polymer versus glucose-containing solutions at their original pH on the oxidative metabolism of the cells showed a highly significant difference (P < 0.0001) in favor of glucose polymers for H202 production of PMNLs (7.78 +/- 4.5 nmol cytochrome C reduction/10(6) cells/min v 1.11 +/- 0.67 nmol cytochrome C reduction/10(6) cells/min) and MNs (7.66 +/- 3.6 nmol cytochrome C reduction/10(6) cells/min v 1.29 +/- 0.86 nmol cytochrome C reduction/10(6)cells/min). Correspondingly, PMNLs and MNs incubated in glucose polymers showed a significantly higher chemiluminescence response irrespective of the stimulant used (P < 0.0001). Applying the killing assay on PMNLs also revealed a significantly higher percentage of inactivated bacteria (45.5% +/- 11.0% v 29.2% +/- 15.5%; P < 0.05). After adjustment of pH to 7.4, a significant difference could only be found for H202 production of PMNLs in favor of glucose polymers (16.73 +/- 6.98 nmol cytochrome C reduction/10(6) cells/min v 11.65 +/- 5.37 nmol cytochrome C reduction/10(6) cells/min; P < 0.05). In addition, we compared the glucose-polymer solution to an otherwise equally composed equiosmolar solution that contained 0.274% glucose instead of glucose polymers. No significant differences were detected with any of the tests applied. Our data suggest that glucose polymer solutions are comparatively less suppressive to phagocytic function than currently used glucose-containing PDFs. This effect may be attributed to the low osmolarity of these solutions.

Adult↗
PubMed1997

In vitro biocompatibility evaluation of a novel bicarbonate-buffered amino-acid solution for peritoneal dialysis.

BACKGROUND: Conventional lactate-buffered peritoneal dialysis fluids containing glucose as the osmotic agent have been shown to compromise important peritoneal host defence functions. The current study employed an in vitro model using activated peripheral blood mononuclear leukocytes (PBMC) for the preclinical biocompatibility assessment of a novel bicarbonate-buffered peritoneal dialysis fluid containing 1.0% amino acids as the osmotic agent. METHODS: PBMC (5 x 10(6)/ml) were pre-exposed (10-30 mm, 37 degrees C) to bicarbonate-buffered 1% amino-acid solution, bicarbonate- or lactate-buffered 1.5% glucose fluid, or control medium (RPMI). The cells were then washed and stimulated for 2 h at 37 degrees C in RPMI containing 100 ng/ml E.coli endotoxin from strain O55:B5. The cytokines IL-6 and TNF alpha in cell supernatants were assessed using specific enzyme immunoassays, cytokine mRNA expression by reverse transcription polymerase chain reaction. RESULTS: Short, i.e. 10 min, exposure to conventional, lactate-buffered glucose fluid resulted in a significant and time-dependent inhibition of cytokine release and mRNA expression by activated PBMC, whereas the cytokine response was improved even following prolonged (up to 2 h) exposure to bicarbonate-buffered 1% amino-acid solution or bicarbonate-buffered 1.5% glucose fluid. CONCLUSIONS: Our results suggest that very short, i.e. potentially clinically relevant, exposure to conventional dialysis fluid impairs the cytokine response by activated leukocytes. In this respect, the use of bicarbonate-buffered solutions containing 1.0% amino acids or 1.5% glucose may result in improved biocompatibility properties.

Amino Acids↗
PubMed1997

Improved cytosolic free calcium mobilization and superoxide production in bicarbonate-based peritoneal dialysis solution.

BACKGROUND: Intraperitoneal phagocytes play an important role in local host defence to prevent CAPD peritonitis. The intracellular calcium [Ca2+]i is thought to be involved in the regulation of various cell functions. This study therefore investigates the effect of lactate-based dialysis solution (LBDS) and bicarbonate-based dialysis solution (BBDS) on cytosolic free calcium mobilization and superoxide production (SP) as important steps in signal transduction and bacterial killing. METHODS: We studied changes in [Ca2+]i and SP following stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) in polymorphonuclear neutrophils (PMNs) incubated in either LBDS-pH 5.2, LBDS adjusted to pH 7.4, 1:10 diluted spent and fresh LBDS or BBDS-pH 7.4 with different glucose concentrations, comparing the data with cells treated with Hanks buffer (HBSS) pH 7.4 as control. To elucidate the effect of glucose and lactate PMNs were additionally incubated in HBSS-pH 7.4, containing glucose (HBSS-Glu-pH 7.4) or lactate (HBSS-Lact-pH 7.4) in the same concentrations as contained in CAPD solutions and tested as above. PMNs were isolated from healthy blood donors and incubated with dialysis solution 10 min prior to stimulation with fMLP. RESULTS: [Ca2+]i mobilization and SP were completely inhibited in PMNs incubated in LBDS pH 5.2. pH adjustment of LBDS to 7.4 and 1:10 dilution of spent and fresh LBDS corrected some of the suppression of the calcium influx and superoxide production. BBDS pH 7.4, however, preserved physiological cell function significantly better at low (1.5 and 2.3%) glucose concentrations. CONCLUSION: In comparison to conventional lactate-based dialysis solution, pH adjusted and 1:10 diluted LBDS, bicarbonate-based dialysis solution is more biocompatible since it preserves significantly better neutrophil cell functions.

Bicarbonates↗
PubMed1997

In vivo and in vitro effects of amino-acid-based and bicarbonate-buffered peritoneal dialysis solutions with regard to peritoneal transport and cytokines/prostanoids dialysate concentrations.

BACKGROUND: Increasing evidence suggests that conventional PD solutions are detrimental to host defence mechanisms of peritoneal cells. We tested a new amino-acid-based and bicarbonate-buffered PD solution under in vivo and in vitro conditions. METHODS: During a prospective, cross-over randomized, intraindividual study 10 CAPD patients were investigated with three different solutions: Amino/Bic, 1% amino acid, 34 mmol/l bicarbonate; Glu/Bic, 1.5% glucose, 34 mmol/l bicarbonate; and Glu/Lac, 1.5% glucose, 35 mmol/l lactate. A PET was performed and transport properties (clearance, D/P ratio, MTAC) were calculated. Prostanoid and cytokine concentrations were measured in serum and the 6 h effluent. Using an in vitro model, mononuclear leukocytes of healthy donors were also incubated with the test fluids. In vivo results. Peritoneal clearance and MTAC of small solutes (creatinine, urea) were not significantly altered by amino acids or bicarbonate. Peritoneal permeability and transperitoneal excretion of higher-weight protein molecules (beta 2-microglobulin, albumin, IgG) were increased with Amino/Bic compared to Glu/Lac (P < 0.05) (D/P ratio albumin: Amino/Bic, 0.027 +/- 0.003; Glu/Bic, 0.023 +/- 0.003; Glu/Lac, 0.022 +/- 0.002). Application of Amino/Bic was accompanied by an increased effluent concentration of Il-6, Il-8, TNF alpha, PGE2, and 6-keto-PGF1a (P < 0.05). Dialysate nitrite/nitrate and cGMP concentrations (as indicators of NO generation) did not differ between the solutions. In vitro results. Both bicarbonate fluids demonstrated a better preservation of the mitochondrial dehydrogenases activity (MTT assay) compared to Glu/ Lac (P < 0.01) (Amino/Bic: 80.6 +/- 3.2%; Glu/Bic: 86.0 +/- 1.8%; Glu/Lac, 64.9 +/- 2.3%, referred to RPMI as control). Constitutive and LPS stimulated release of Il-1 beta and Il-6 was less suppressed with both bicarbonate fluids (P < 0.05) (LPS-stim. Il-6 release: Amino/Bic, 33.0 +/- 6.6%; Glu/Bic, 65.5 +/- 10.3%; Glu/Lac, 1.5 +/- 0.7% referred to RPMI). CONCLUSION: Application of an amino-acid/bicarbonate solution resulted in a small but significant increase in peritoneal permeability. Also increased concentrations of various cytokines/prostanoids were measured in the effluent. According to in vitro testing with mononuclear phagocytes both bicarbonate-buffered fluids were to the same extent less inhibitory to certain cell functions than lactate-buffered solution.

Adult↗