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A new stable bicarbonate dialysis solution for peritoneal dialysis: preliminary report.

This paper describes the use of glycylglycine to prepare dialysis solution containing bicarbonate, calcium and magnesium. Bicarbonate with glycylglycine form a buffer with a constant pH of 7.35, which prevents reaction with calcium or magnesium and the formation of insoluble carbonate salts. This bicarbonate-based solution is stable over long periods and can be used with the same simplicity and convenience as lactate solution for peritoneal dialysis (PD) in humans.

Animals↗

Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis.

UNLABELLED: Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis. BACKGROUND: Patients on automated peritoneal dialysis (APD) usually receive larger volumes of dialysis solution and more frequent, shorter exchanges than patients on continuous ambulatory peritoneal dialysis (CAPD), and therefore are likely to derive greater benefit from more physiologic solutions. METHODS: Peritoneal dialysis solutions containing 25 mmol/L bicarbonate and either 10 or 15 mmol/L lactate were compared with standard lactate solutions (35 or 40 mmol/L) in two prospective, open-label studies of patients on APD. Each study included a 2-week baseline period (lactate solution), a 6-week treatment period (bicarbonate/lactate solution), and a 2-week follow-up period (same lactate solution as baseline). Biochemical analyses and assessments of vital signs and safety parameters were conducted at baseline, every 2 weeks during treatment, and at the end of the follow-up period. A product use questionnaire was administered in one study at the end of treatment. RESULTS: A statistically significant rise in plasma bicarbonate (approximately 2 mmol/L) occurred when patients switched from a lactate solution to the bicarbonate/lactate solution with equimolar buffer concentration (P < 0.001 for each solution). Plasma bicarbonate decreased by 1.16 mmol/L after a switch from lactate 40 mmol/L to bicarbonate/lactate 35 mmol/L (P < 0.001). When patients switched to bicarbonate/lactate 35, the majority of individual venous plasma bicarbonate values were in the normal range. A switch from a lower calcium (1.25 mmol/ L) lactate solution to a higher calcium (1.75 mmol/L) lactate/bicarbonate solution resulted in a statistically significant rise in serum calcium (0.06 mmol/L, P < 0.018). The product use questionnaire revealed improvements in symptoms, including reduced pain on infusion. CONCLUSION: Bicarbonate/lactate solutions may be used safely and effectively in patients on APD. The availability of 2 formulations with different buffer and calcium content provides flexibility for the control of acidosis as well as calcium balance.

Automation↗

Impact on peritoneal membrane of use of icodextrin-based dialysis solution in peritoneal dialysis patients.

The usefulness of icodextrin-containing peritoneal dialysis (PD) solution for the management of body fluid and blood pressure has been reported. However, icodextrin PD solution is a foreign solution in the body, and the possible induction of intraperitoneal inflammation has been reported. In this study, we investigated at 6-month intervals the influence of icodextrin solution on peritoneal permeability and inflammatory reactions in patients in whom glucose solution had been changed to icodextrin solution for the overnight dwell. We enrolled 9 anuric PD patients (5 men, 4 women) of mean age 58 +/- 5.9 years (range: 45.6-64.8 years) into the study. The patients' mean duration of PD was 61.9 +/- 42 months (range: 6.7-142.5 months). The cause of end-stage renal disease was chronic glomerulonephritis in all patients. For evaluation ofperitoneal permeability, we performed peritoneal equilibration tests (PETs) immediately after an overnight dwell and determined the dialysate-to-plasma ratios of creatinine (D/P Cr), beta2-microglobulin (D/P beta2m), albumin (D/P Alb), immunoglobulin G (D/P IgG), and alpha2-macroglobulin (D/P alpha2m). We also measured interleukin-6 (IL-6) and fibrinogen degradation products (FDPs) in overnight effluent as indices of inflammation and of the fibrinolysis-coagulation system. The evaluation was performed every 6 months for 24 months. The FDPs in effluent increased significantly at 6 months after the change to icodextrin solution, and IL-6 tended to increase. The D/P beta2m, D/P Alb, D/P IgG, and D/P alpha2m all significantly increased in the course of follow-up. In the PETs, the D/P Cr increased slightly, but the change was nonsignificant. At 30 months after the change to icodextrin solution, 1 patient was diagnosed as having a risk of encapsulating peritoneal sclerosis (pre-EPS). In this patient, rapid increases in IL-6, D/P Cr and macromolecular and small molecular D/P by PET were noted after the change to icodextrin solution. Steroids were administered after the diagnosis of pre-EPS, with the result that the IL-6 level rapidly decreased and the D/P Cr and D/P of small molecules and macromolecules slightly decreased. Icodextrin dialysis solution increased peritoneal permeability. Although the cause was unclear, icodextrin may have changed peritoneal reactivity. Long-term use of icodextrin PD solution requires further investigation.

Albumins↗

Altered cellular biosynthesis in human peritoneal mesothelial cells exposed to dialysis solutions.

Peritoneal dialysis (PD) solutions can produce changes in the peritoneal membrane and structure which are related to the high glucose concentrations and low pH of these solutions. This study was designed to examine the effects of high glucose (76-214 mM) and low pH (5.3) solutions on human peritoneal mesothelial cells in culture. Changes in mesothelial cell biosynthesis and cell numbers were evident within 2 hours of exposure to unmodified dialysis solutions. In the development of new dialysis solutions, human peritoneal mesothelial cells in culture provide a good in vitro model to determine potential toxicity.

Animals↗

Slow continuous ultrafiltration with bound solute dialysis.

Bound solute dialysis (BSD), often referred to as "albumin dialysis" (practiced clinically as the molecular adsorbents recirculating system, MARS, or single-pass albumin dialysis, SPAD) or "sorbent dialysis" (practiced clinically as the charcoal-based Biologic-DT), is based upon the thermodynamic principle that the driving force for solute mass transfer across a dialysis membrane is the difference in free solute concentration across the membrane. The clinically relevant practice of slow continuous ultrafiltration (SCUF) for maintenance of patients with liver failure is analyzed in conjunction with BSD. The primary dimensionless operating parameters that describe SCUF-BSD include (1) beta, the dialysate/blood binder concentration ratio; (2) kappa, the dialyzer mass transfer/blood flow rate ratio; (3) alpha, the dialysate/blood flow rate ratio; and, (4) gamma, the ultrafiltration/blood flow rate ratio. Results from mathematical modeling of solute removal during a single pass through a dialyzer and solute removal from a one-compartment model indicate that solute removal is remarkably insensitive to gamma. Solute removal approaches an asymptote (improvement in theoretical clearance over that obtainable with no binder in the dialysate) with increasing beta that is dependent on kappa and independent of alpha. The amount of binder required to approach the asymptote decreases with increasing solute-binder equilibrium constant, i.e., more strongly bound solutes require less binder in the dialysate. The results of experimental observations over a range of blood flow rates, 100 to 180 mL/min, dialysate flow rates, 600 to 2150 mL/h, ultrafiltration rates, 0 to 220 mL/h, and dialysate/blood albumin concentration ratios, beta = 0.01 to 0.04, were independently predicted remarkably well by the one-compartment model (with no adjustable parameters) based on BSD principles.

Albumins↗

Dialysis solutions buffered with lactate or bicarbonate: in vitro comparison of two dialysis solutions on human peritoneal cell growth from ESRD and non-ESRD patients.

In order to evaluate the injury to the mesothelial cell layer during long-term peritoneal dialysis (PD), a dialysis solution (solution A), buffered with bicarbonate, stabilized with 10 mmol/L glycylglycine, and sterilized by filtration (0.22 micron double filtration, pH = 7.4), was compared to traditional heat sterilized lactate solution (solution B) on human mesothelial cell cultures. The respective effects of both solutions were evaluated on first passage cells by 3H thymidine incorporation after 72-, 96-, 120-, and 144-h contact. Mesothelial cells to be cultured were obtained from the omentum biopsies of 7 end-stage renal disease (ESRD) patients (during first peritoneal catheter placement) and from 7 non-ESRD patients undergoing abdominal surgery. Solution A (diluted 1/5) induced a time-dependent stimulation of growth in 6 cases of ESRD patient cell cultures, and inhibition occurred only in 1 case. Stimulation was also observed in 5 non-ESRD patient cell cultures, and no effect occurred in 2 cases. Solution B inhibited growth in all the cultures except in 1 case of an ESRD patient in which no effect was observed. This study shows that solution A induced mesothelial cell proliferation, while an inhibitory effect of solution B was observed. No significant differences were observed between the sensitivity of mesothelial cells from ESRD and non-ESRD patients. Further analysis will be carried out to identify precisely the cause of the differences observed: buffer or glycylglycine by themselves and/or glucose by-products.

Aged↗

Peritoneal reactions to particulate matter in peritoneal dialysis solutions.

Peritoneal dialysis solutions were chemically injected into the peritoneal cavity of mice. A high percentage of the injected animals showed particulate matter in the peritoneal membranes associated with an inflammatory reaction. This was prevented by final filtration of the solutions through 0.22 and 0.45 mu filters. It is recommended that all chronic peritoneal dialysis be performed through a final filter.

Animals↗

Effects of inhibition of the polyol pathway during chronic peritoneal exposure to a dialysis solution.

BACKGROUND: Peritoneal dialysis with glucose- and lactate-containing dialysis solutions stimulates peritoneal angiogenesis and fibrosis. These serious side effects can also be induced by chronic peritoneal exposure to dialysis solutions in nonuremic rats. The high glucose concentrations of the dialysis solutions may saturate physiological glucose metabolism pathways and stimulate the polyol pathway that has been described to damage nerves and vessels in diabetes mellitus. To investigate the role of the polyol pathway in the development of fibrosis and angiogenesis during chronic peritoneal exposure, the rate-limiting aldose reductase activity in the polyol pathway was inhibited in a chronic peritoneal exposure model in the rat, in which different administration routes were compared. EXPERIMENTAL PROCEDURES: Three groups of rats received daily intraperitoneal infusion with lactate/glucose (3.86%)--containing dialysate via a peritoneal catheter with a subcutaneous puncture device, for 14 weeks: group 1 received only the dialysis solution, groups 2 and 3 received, in addition, zopolrestat, administered either orally (group 2) or intraperitoneally (group 3). After sacrifice, omental tissue was examined by histology for the presence of fibrosis (Picro Sirius Red) and the number of blood vessels (CD31). RESULTS: Histology revealed significantly less Picro Sirius Red-positive tissue in perivascular areas of both experimental groups and submesothelial areas of the oral group in comparison to the control group. There were significantly fewer CD31-positive vessels perfield in both groups treated with zopolrestat compared to the infusion-only group: group 2, 9 (7 - 12); group 3, 17 (13 - 38), compared to group 1, 37 (32 - 39), p < 0.05. CONCLUSION: The combination of peritoneal exposure to dialysis fluids and administration of zopolrestat, a newly developed inhibitor of aldose reductase activity, resulted in less fibrosis and fewer peritoneal vessels than exposure to dialysis fluids only, in a long-term exposure model in the rat. Inhibition of the polyol pathway may thus offer an important contribution to allow long-term continuation of peritoneal dialysis.

Aldehyde Reductase↗

Generalized dilation of the visceral microvasculature by peritoneal dialysis solutions.

OBJECTIVES: Conventional peritoneal dialysis solutions are vasoactive. This vasoactivity is attributed to hyperosmolality and lactate buffer system. This study was conducted to determine if the vasodilator property of commercial peritoneal dialysis solutions is a global phenomenon across microvascular levels, or if this vasodilation property is localized to certain vessel types in the small intestine. DESIGN: Experimental study in a standard laboratory facility. INTERVENTIONS: Hemodynamics of anesthetized rats were monitored while the terminal ileum was prepared for in vivo intravital microscopy. Vascular reactivity of inflow arterioles (A1), branching (A2), and arcade, as well as pre-mucosal (A3) arterioles was assessed after suffusion of the terminal ileum with a non-vasoactive solution or a commercial 4.25% glucose-based solution (Delflex; Fresenius USA, Ogden, Utah, USA). Vascular reactivity of three different level venules was also assessed. Maximum dilation response was obtained from sequential applications of the endothelial-dependent dilator, acetylcholine (10(-5) mol/L), and the endothelial-independent nitric oxide donor, sodium nitroprusside (NTP; 10(-4) mol/L). RESULTS: Delflex induced an instant and sustained vasodilation that averaged 28.2% +/- 2.4% of baseline diameter in five different-level arterioles, ranging in size between 7 mu and 100 mu. No significant vascular reactivity was observed in three different-level venules. Delflex increased intestinal A1 blood flow from baseline 568 +/- 31 nL/ second to 1,049 +/- 46 nL/sec (F= 24.7, p< 0.001). Similarly, intestinal venous outflow increased to 435 +/- 17 nL/sec from a baseline outflow of 253 +/- 59 nL/sec (F= 4.7, p < 0.05). Adjustment of the initial pH of Delflex from 5.5 to 7.4 resulted in similar microvascular responses before pH adjustment. CONCLUSIONS: Ex vivo exposure of intestinal arterioles to conventional peritoneal dialysis solutions produces a sustained and generalized vasodilation. This vasoactivity is independent of arteriolar level and the pH of the solution. Dialysis solution-mediated vasodilation is associated with doubling of A1 intestinal arteriolar blood flow. Addition of NTP at an apparent clinical dose does not appear to produce any further significant arteriolar dilation than that induced by dialysis solution alone. Experimental data that estimate the exchange vessel surface area per unit volume of tissue will be required to make a correlation with permeability in order to extrapolate our findings to clinical in vivo conditions.

Animals↗

A comparison of hetastarch and peritoneal dialysis solution for intraperitoneal chemotherapy delivery.

AIM: Intraperitoneal chemotherapy administration results in high drug concentration locally with low systemic toxicity. We compared the pharmacokinetics of paclitaxel infused intraperitoneally in two isotonic carrier solutions, 1.5% dextrose peritoneal dialysis solution (peritoneal dialysis solution) and hetastarch (6% hydroxyethyl starch), a high molecular weight solution. METHODS: Twenty patients with peritoneal carcinomatosis were randomized into one of two groups to receive early postoperative intraperitoneal chemotherapy with paclitaxel for 5 consecutive days following cytoreductive surgery. One group (8 patients) received paclitaxel in one litre of peritoneal dialysis solution; the other group (12 patients) received paclitaxel in one litre of hetastarch. Samples of peritoneal fluid and venous blood were taken during the 23 h dwell time. Volumes of chemotherapy solution were recorded and concentrations of paclitaxel determined by high performance liquid chromatography. RESULTS: Hetastarch clearance from the peritoneal cavity was reduced when compared to peritoneal dialysis solution. The mean volume of fluid remaining in the peritoneal cavity at 23 h was 900 ml +/-373.7 (SD) with hetastarch, and 285 ml (+/-157.5) with peritoneal dialysis solution (P=0.0022). The mean total amount of paclitaxel in the peritoneal cavity at 23 h was 2.597 mg (+/-1.57) with hetastarch and 0.772 mg (+/-0.667) with peritoneal dialysis solution (P=0.0152). CONCLUSION: These data show that hetastarch increased the exposure of peritoneal surfaces to paclitaxel by increasing the volume of solution with no decrease in drug concentration. Residual tumour cells within the peritoneal cavity may show an increased response to paclitaxel with hetastarch as a carrier solution.

Adult↗

Is there a need for low sodium dialysis solution for peritoneal dialysis patients?

Cardiovascular disease is a leading cause of death in patients with end-stage renal disease (ESRD), and hypertension and volume expansion are highly prevalent in long-term peritoneal dialysis (PD) patients. The ADEMEX study made it clear that increased small-solute clearance does not lead to better outcomes. To manage the problem, current clinical practice uses strategies of dietary salt and fluid restriction, diuretics, antihypertensive drugs, icodextrin, extra day dwells, and (as a last resort) PD combined with hemodialysis (HD) or switch to HD. Nevertheless, the prevalence of hypertension remains alarmingly high. In this article, we briefly discuss the therapeutic measures currently available for treating hypertension and volume overload in PD patients, the limitations of those measures, and the possibility of increasing sodium removal by reducing the dialysate sodium level.

Antihypertensive Agents↗

Comparison of fast peritoneal equilibration tests with 1.36 and 3.86% dialysis solutions.

At present dialysis solutions with different glucose concentrations are used for the peritoneal equilibration test (PET) and Fast-PET in peritoneal dialysis (PD). We compared the results of two Fast-PETs, using 1.36 and 3.86% solutions sequentially in 30 patients on PD treatment, to obtain information on peritoneal transport (D/P-4 h) and ultrafiltration rates. Creatinine, phosphorus and urea D/P-4 h in the two Fast-PETs were not statistically different, unlike those for potassium, beta 2-microglobulin and glucose. The creatinine and phosphorus D/P-4 h values in particular proved to be uninfluenced by the different dialysis solutions. The lack of correlation between the two Fast-PET ultrafiltration values confirmed the difficulty in interpreting this parameter, above all in the case of non-homologous Fast-PETs. We obtained useful indications for comparing different Fast-PET results, but were unable to reach a decisive conclusion regarding the best of the two dialysis solutions for this test.

Aged↗

Prevention of membrane damage in patient on peritoneal dialysis with new peritoneal dialysis solutions.

Peritoneal dialysis (PD) is now an established and successful alternative to hemodialysis. Multiple studies have confirmed its equivalent dialysis adequacy, mortality and fluid balance status, at least for the first 4-5 years. Peritoneal membrane failure is now one of the leading cause of technique failure. This review describes the role of glucose, glucose degradation product, pH, lactate, advanced glycosylation end product (AGE) in causing this membrane damage, and gives insight how the use of newer peritoneal dialysis fluids (PDFs) containing icodextrin, amino acids and bicarbonate buffer can prevent peritoneal membrane damage.

Dialysis Solutions↗

Aluminum determination in whole blood, dialysis solution, and tap water samples from Maracaibo dialysis units (Venezuela) by graphite furnace atomic absorption spectrometry.

Patients with chronic renal failure (CRF) on periodical hemodialysis may accumulate aluminum in tissues and show typical disorders such as dialysis encephalopathy, osteodystrophy, and microcytic anemia. Aluminum contamination of the water used to prepare the dialysis solution (dialysate) is one of the metal sources that may affect people under hemodialysis, especially in units in which untreated water is used. Graphite furnace atomic absorption spectrometric methods for aluminum determination in whole blood, dialysis solution, and tap water samples from CRF patients were developed, based upon the use of the same furnace temperature program. Samples were diluted 4-fold with 0.6% triton X-100 (whole blood) or with 0.01 mol/L nitric acid (dialysis solution and tap water) and analyzed by aqueous standard (blood and tap water) or matrix-matching standard (dialysis solution) calibration curves. The characteristic masses were 33.8, 11.3, and 19.5 pg Al/0.0044 A.s for whole blood, dialysate, and tap water, respectively. In the diluted solutions, the detection limits (2 sigma) for the described methods were 0.5 microgram/L Al (whole blood), 0.4 microgram/L Al (dialysate), and 0.4 microgram/L Al (tap water). The methods were applied to samples from several CRF patients under hemodialysis at Maracaibo University hospital. The data revealed extremely high aluminum levels, which corresponded to the symptoms of dialysis encephalopathy and/or osteodystrophy showed by some of them. The proposed methods are reliable and reproducible.

Aluminum↗

The choice of dialysis solutions in pediatric chronic peritoneal dialysis: guidelines by an ad hoc European committee.

OBJECTIVE: To provide guidelines on choosing dialysis solutions for children on chronic peritoneal dialysis (PD). SETTING: European Paediatric Peritoneal Dialysis Working Group. DATA SOURCE: Literature on the application of PD solutions in children (Evidence), and discussions within the group (Opinion). CONCLUSIONS: Glucose is the standard osmotic agent for PD in children (Evidence). The lowest glucose concentration needed should be used (Opinion). Low calcium solution (1.25 mmol/L) should be applied, wherever possible, with careful monitoring of parathyroid hormone levels (Opinion). The use of amino acid-containing dialysis fluids can be considered in malnourished children, although aggressive enteral nutrition is preferred (Opinion). There is insufficient evidence documenting the efficacy of intraperitoneally administered amino acids (Evidence). When ultrafiltration and/or solute removal are insufficient, polyglucose solutions are a welcome addition to the treatment of children on nocturnal intermittent PD (Evidence). However, in the absence of any reported long-term experience with children, their use must be closely monitored (Opinion). Bicarbonate would appear to be the preferred buffer for PD in children, but more in vivo studies are required before it replaces the present lactate-containing solutions (Evidence/Opinion).

Acetates↗

[The impact of glucose absorbed from dialysis solution on body weight gain in peritoneal dialysis treated patients].

A proportion of peritoneal dialysis (PD) patients experience substantial body weight (BW) gain with time. It is caused by fat tissue accumulation or fluid retention. It is believed that fat tissue accumulates due to caloric contribution of glucose absorbed from dialysis solution or to the mitochondrial fat regulatory uncoupling protein (UCP) gene polymorphism. This study examined BW fluctuations in 40 patients (24 females, 16 males), treated by PD at least 36 months (initial mean age 54.50+/-9.00 years, mean BW 68.00+/-8.50 kg and mean height 164.00+/-8.50 cm), relation of the BW fluctuation and caloric contribution of glucose absorbed from dialysis solution and characteristics of the patients with BW gain. Initial BW increased after 6, 12, 24 and 36 months by 5.90+/-3.50 kg, 7.90+/-4.90 kg, 9.50+/-5.00 and 11.00+/-5.00 kg, or for 8.68, 11.62, 13.97 and 16.18% of the initial value, respectively. After the first 6 and 12 months 38 patients gained weight, 39 after 24 and all 40 patients after 36 months. There was not significant correlation between BW gain and caloric contribution of glucose absorbed from dialysis solution. Female patients had initially lower BW, but for the first 12 months period significantly increased BW more than males, and not for the other observed periods. High transporters (patients with higher transport, higher transmission of glucose from peritoneal solution into the blood, and urea and creatinine in the opposite direction, with rapid decrement of osmolality gradient between dialysate and blood that is necessary for excessive fluid elimination), had lower initial BW and, although without statistical significance, only within the first period increased BW more than low transporters. In conclusion, with time BW gain was found in all the PD dialysis patients, it was not related to caloric contribution of glucose absorbed from dialysis solution, and women and high transporters increased BW weight more than men and low transporters in the first year of treatment. The BW gain is at least in part caused by fluid retention.

Energy Intake↗

Analysis of non enzymatic glycosylation in vivo: impact of different dialysis solutions.

BACKGROUND: Glucose-containing dialysis solutions in peritoneal dialysis (PD) patients induce non enzymatic glycosylation (NEG) within the peritoneal cavity. The subsequent formation of advanced glycosylation end-products (AGEs) may be implicated in the functional deterioration of the peritoneal membrane in long-term PD patients. AIM OF THE STUDY AND PARAMETERS: Measurement of NEG by the determination of percent glycation of albumin and IgG (GP), and of AGEs by measuring pentosidine content of protein in 4-hour effluents (Peff) and serum. SUBJECTS: In 5 patients each, a comparison was made between 3.86% glucose and 1.36% glucose (GP and Peff), and between 3.86% glucose and 7.5% icodextrin (Peff). Nine patients with clinically severe ultrafiltration failure (UFF) were compared to nine patients treated with PD for 1 month. Six of the patients with UFF were treated with non glucose dialysis solutions and Peff was studied again after 6 weeks. RESULTS: No difference was found between Peff comparing 3.86% glucose to either 1.36% glucose or icodextrin. GP were higher in 3.86% glucose than in 1.36%. Glycated/non glycated (G/NG) protein clearance ratios were 1.29 for albumin and 1.12 for IgG (p = 0.003). In contrast to GP, both Peff and serum pentosidine were higher in the UFF patients than in the recently started patients. Peff, but not GP, correlated with duration of PD (r = 0.67, p = 0.04). In 5 of 6 patients treated with non glucose dialysate, Peff decreased while serum pentosidine was stable. DISCUSSION: These data show that 4-hour Peff contents are not influenced by glucose concentration or osmolality, in contrast to GP. The relation between Peff and duration of PD, and the effect of non glucose dialysate on Peff, suggest that long-term glucose exposure is an important determinant of membrane glycosylation. Thus Peff probably reflects the long-term effects of intraperitoneal glycosylation of peritoneal membrane proteins. Treatment with non glucose dialysis solutions may result in "washout" of glycosylated proteins from the peritoneal membrane.

Albumins↗