Reduced complications during hemodialysis by automatic blood volume controlled ultrafiltration.

BACKGROUND: Intradialytic morbid events (IMEs, mostly hypotension) are frequent complications during hemodialysis (HD). This study investigated whether automatic feedback control via adjustment of the ultrafiltration rate reduces IME frequency. METHODS: In this multi-center cross-over study, 56 hypotension-prone patients were treated both with standard HD (sHD, applying a constant ultrafiltration rate) and HD applying a blood volume controlled ultrafiltration rate (cHD). The relative blood volume (RBV) was continuously monitored. The individual relative blood volume limit (RBVcrit ) was determined from the measured RBV during initial sHD. During cHD, the ultrafiltration rate was automatically adjusted to keep the actual RBV above RBVcrit. RESULTS: In 3,081 HD treatments, slightly fewer IMEs were observed during cHD than during sHD (0.785+/-0.613 versus 0.695+/-0.547 per treatment, P=0.144). Less symptomatic events were seen during cHD: -13% for symptomatic hypotension (0.594 versus 0.685 per treatment, P=0.120), and -32% for cramps (0.049 versus 0.072 per treatment, P=0.009). Thirty-one patients with the highest IME rate (IME in at least every second treatment) especially benefited from cHD: 1.185+/-0.554 versus 0.979+/-0.543 IME per treatment (P=0.004). The reduction in blood pressure (BP) and the increase in heart rate were lower during the treatments with cHD than with sHD: systolic BP: -18.8+/-26.7 versus -22.2+/-28.9 mmHg (P=0.007), diastolic BP: -7.8+/-14.8 versus -9.1+/-15.3 mmHg (P=0.064), heart rate: 1.8+/-10.4 versus 2.3+/-11.6 per minute (P=0.014). Neither treatment duration nor ultrafiltration volume was significantly different between cHD and sHD. CONCLUSION: For cHD, less intradialytic morbid events were observed than for sHD, and pre- to post-dialytic changes in blood pressure and heart rate were less pronounced.

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.

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.

Solutions for APD: special considerations.

Automated peritoneal dialysis (APD) has become the fastest growing dialysis modality in Europe and the United States in recent years. Freedom from daytime exchanges, flexibility of prescription, performance in recumbent position leading to enhanced treatment efficacy, and a decreased incidence of peritonitis are the main advantages of APD over CAPD. Studies on new developments of glucose-based PD fluids were performed predominantly in CAPD patients. High volumes and frequent APD cycles in patients may aggravate the adverse effects of standard CAPD fluids on the peritoneal membrane with increasing time on PD. New, glucose-based PD fluids with neutral pH, very low concentrations of glucose degradation products (GDPs), containing either lactate or bicarbonate as buffering substances have been introduced into clinical use recently. With these new fluids, various in vitro, ex vivo, and in vivo studies could demonstrate a better preservation of peritoneal cell viability and growth, less inhibited secretory cell functions, a significant reduction in the formation of advanced glycation end products (AGEs), and clinical signs for an improved preservation of peritoneal mesothelial cells indicated by an increase in effluent CA125. One has to be aware, however, that uremia per se prior to initiation of PD, as well as during PD treatment itself, directly impacts on peritoneal membrane structural changes so that new, more biocompatible PD fluids may not be completely sufficient to prevent morphologic and functional changes of the membrane. Due to a strong sodium sieving during APD, PD fluids with sodium concentrations of 125-130 mmol/L may be beneficial. Systematic calcium kinetic studies have not yet been performed in APD patients. APD fluids should offer a calcium concentration range of 1.0-1.75 mmol/L in order to enable an individualized APD prescription. For long-term APD treatment, better knowledge of peritoneal membrane physiology and PD kinetics should promote individualization of prescriptions. New, pH-neutral PD solutions with minimized amounts of GDPs may be a significant step forward to improved membrane preservation during long-term APD treatment.

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.

Continuous flow peritoneal dialysis: solution formulation and biocompatibility.

When peritoneal dialysis was introduced several years ago an important alternative dialysis therapy to hemodialysis was made available for the treatment of end-stage chronic disease. However, a continuous search for new developments and technologies is necessary to find the optimal peritoneal dialysis fluid (PDF) to preserve peritoneal membrane function as long as possible. Conventional PDFs are known to compromise the functional integrity of the peritoneal membrane as a consequence of their acidic pH in combination with their high lactate content, as well as the high concentrations of glucose and glucose degradation products (GDPs) present in currently used conventional solutions. Novel solutions such as bicarbonate-buffered PDF (at neutral pH) display improved in vitro biocompatibility as compared to conventional, acidic lactate-buffered PDF. Since these novel solutions are manufactured in dual-chambered bags they also contain fewer GDPs, thus further reducing their potential toxicity and protein glycation. Clinically the novel solutions reduce inflow pain and improve peritoneal membrane transport characteristics, ultrafiltration capacity, and effluent markers of peritoneal membrane integrity. The concept of continuous flow peritoneal dialysis (CFPD) is another approach to optimize PDF. The technique of CFPD not only enables the individualization of acid-base correction by variable concentrations of HCO3- but may also help to restore peritoneal cell functions by neutral pH, reduced glucose load, diminished GDP content, and reduced advanced glycation end product (AGE) formation, thereby potentially contributing to the improved preservation of peritoneal membrane function.

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.

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.

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.

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.

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.

Liver cell reactive components in peritoneal dialysis fluids.

Metabolic changes in peritoneal dialysis (PD) patients are an important aspect concerning long-term outcome. Liver plays the main role in regulating metabolism. The effects of peritoneal dialysis fluids (PDF) on liver cell function are scarcely investigated. Therefore, we investigated the effects of PDF, different in some components, on liver cell metabolism in vitro. Metabolic activity (MTT), cell integrity (LDH release), proliferation (BrdU incorporation) and synthesis of albumin and transferrin are measured by incubating HepG2 cells for 3 h and 24 h with six different PDFs: (a) lactate-buffered, pH5.5: PDF I (1.5% gluc.); PDF II (4.5% gluc. ); (b) bicarbonate-buffered, pH7.4: PDF III (1.5% gluc.), PDF IV (4. 5% gluc.); (c) amino acid-based solutions, pH 7.4: PDF V (low AA level) and PDF VI (high AA level). Metabolic activity of bicarbonate-treated cells is greatly enhanced in comparison to lactate-buffered PDFs. These findings are confirmed by proliferation data. Synthesis of albumin and transferrin is significantly enhanced by amino acid-based solutions. Our data demonstrate, that lactate-buffered PDF impair liver cells much stronger than bicarbonate-buffered PDF. pH is the parameter which contributes to cytotoxicity and impaired metabolism to a major extent. In contrast to glucose-containing solutions, amino acid-based PDF stimulate protein synthesis in liver cells.

An amino acid-based peritoneal dialysis fluid buffered with bicarbonate versus glucose/bicarbonate and glucose/lactate solutions: an intraindividual randomized study.

OBJECTIVE: In order to study acute metabolic changes and peritoneal transport, amino acids as osmotic agent and bicarbonate as buffer were tested as new agents in peritoneal dialysis (PD) solutions. DESIGN: In a prospective, cross-over, randomized, intraindividual study, we investigated the acute metabolic changes following the application of three different PD fluids: (1) a 1% amino acid-based PD solution buffered with bicarbonate (34 mmol/L) (Amino/Bic); (2) a 1.5% glucose anhydrous-containing bicarbonate-buffered solution (34 mmol/L) (Glu/Bic); and (3) a conventional 1.5% glucose anhydrous-based dialysis solution with lactate (35 mmol/L) (Glu/Lac). SETTING: University medical center. PATIENTS: Ten nondiabetic patients stable on continuous ambulatory peritoneal dialysis (time on dialysis, 42.5 +/- 21.5 months) were treated and monitored with the test solutions over a 6-hour dwell. Three different study days followed in a randomized order for each patient (interval of 1-3 weeks). Blood and dialysate samples were taken at 0.25, 0.5, 1, 2, 4, and 6 hours. Immediately after the 1-hr dwell (and after sampling), the patients received a standardized breakfast, thereby simulating usual food intake. RESULTS: Following the application of Amino/Bic a significant increase in plasma amino acids occurred, with peak levels (maximum 250% increase) after either the 1-hr or the 2-hr dwell. Before taking the standard meal (0.5 hr, 1 hr), the mean serum glucose level with Amino/Bic was 8% +/- 13% lower than with Glu/Bic (p = 0.06) and 14% +/- 8% lower than with Glu/Lac (p < 0.01). This difference was still significant after the standard breakfast and also for the whole dwell (average serum glucose 0.5-6 hr: Amino/Bic, 91 +/- 6 mg/dL; Glu/Bic, 100 +/- 8 mg/dL; Glu/Lac, 102 +/- 7 mg/dL; p < 0.01 MANOVA). The serum insulin profiles did not differ between the fluids. A transperitoneal protein- and amino acid-related nitrogen loss of 0.49 +/- 0.18 g and 0.48 +/- 0.12 g per dwell was measured using Glu/Bic and Glu/Lac, while a positive balance of 1.80 +/- 0.43 g was achieved with Amino/Bic. The parameters of acid-base status (pH, HCO3, pCO2) remained nearly unchanged in the blood, irrespective of the solution used, while dialysate values differed markedly. No significant differences with respect to ultrafiltration (Amino/Bic, -68 +/- 199 mL/6 hr; Glu/Bic, -51 +/- 89 mL/6 hr; Glu/ Lac, -2 +/- 134 mL/6 hr) and peritoneal creatinine clearance (Amino/Bic, 4.9 +/- 0.6 mL/min; Glu/Bic, 5.1 +/- 0.6 mL/min; Glu/ Lac, 4.8 +/- 0.5 mL/min) were measured. CONCLUSIONS: Our results demonstrate that ultrafiltration and small solute clearance over a 6-hour dwell with a 1% Amino/Bic solution were comparable to those of 1.5% Glu/Bic and 1.5% Glu/Lac. Reduced serum glucose concentrations were found with Amino/Bic and this fluid compensated the transperitoneal protein-nitrogen loss of about three glucose dwells. Bicarbonate buffering (34 mmol/L) did not change blood acid-base status combined with either glucose or amino acids.

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.

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.