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PubMed1999

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↗
PubMed2000

Biocompatibility of new peritoneal dialysis solutions: clinical experience.

The successful development of peritoneal dialysis (PD) during the last two decades has been made possible by using well-established glucose-based solutions with lactate as buffer. On the other hand, awareness has been increasing about the potentially negative effects of the high concentrations of glucose and lactate, and the low pH of conventional PD solutions. This awareness has prompted an intensive effort to search for and test alternative solutions. As a result, three new, more biocompatible solutions-containing either less glucose or less lactate--are available. Amino acid-based solution uses amino acids instead of glucose as the osmotic agent; it is indicated for treatment of malnutrition. The higher pH and absence of glucose in this solution may prevent alterations of the peritoneal membrane caused by acidity and high glucose concentrations. Bicarbonate/lactate-buffered solution contains a physiologic concentration of bicarbonate and a reduced concentration of lactate; it also has a physiologic pH and markedly reduced levels of glucose degradation products (GDPs). Icodextrin-based solution contains icodextrin as the osmotic agent; it is indicated for long dwells, delivering sustained ultrafiltration for more than 16 hours. This iso-osmolar glucose-free solution may reduce peritoneal membrane alterations caused by glucose or the hyperosmolality (or both) of conventional solutions. Clinical experience of the new solutions is now extensive, and their efficacy and safety are well documented. It therefore seems appropriate to state that we have entered a new era of PD therapy. Each of the new solutions may be less damaging to the peritoneal membrane than conventional solution. In addition, they permit better management of malnutrition and fluid status, and may thus help to improve PD patient survival. Although the effects of each of these new solutions have been well described, clinical documentation of the combined use of these new biocompatible PD solutions is still insufficient. However, the results of studies are expected, during the coming years, to support the combined use of the new solutions as the preferred standard practice for PD.

Amino Acids↗
PubMedDate not supplied

Timely initiation of dialysis--single-exchange experience in 39 patients starting peritoneal dialysis.

OBJECTIVE: To establish the effectiveness and patient acceptability of initiating peritoneal dialysis (PD) according to published guidelines. SETTING: A university teaching hospital and a neighboring district general hospital. DESIGN: Nonrandomized prospective pilot study. PATIENTS: 39 patients with a Kt/V > 2.0 attending predialysis clinics at both hospitals agreed to participate in this study. METHODS: Patients were started on a single exchange of dialysate overnight. Dialysis adequacy was monitored at least every 2 months and incremental increases in dialysis were used to maintain combined urinary and dialysis Kt/V above 2.0. Routine laboratory parameters and complications of dialysis were monitored during the follow-up period. RESULTS: The mean weekly Kt/V at initiation of dialysis was 2.09. Median actuarial survival on a single exchange before requiring incremental dialysis was 297 days. At the end of the study period, all patients were still alive: 8 remained on 1 exchange, 18 were on more than 1 exchange, 8 had switched to hemodialysis, and 5 had received renal transplants. During the 12,665 patient-days on single-exchange dialysis, there were 14 hospital admissions of 12 patients. This resulted in a mean of 1.64 hospital days per patient-year for the whole group. During the follow-up period there were 2 episodes of bacterial peritonitis, 3 pleural leaks, 1 patent processus vaginalis, and 1 inguinal hernia that required surgical intervention. The use single daily icodextrin exchanges was associated with a 46% incidence of culture-negative peritonitis. CONCLUSIONS: This pilot study has shown that a timely start of dialysis with a single overnight PD exchange is acceptable to patients. Incremental dialysis as residual renal function falls is easily managed and patients also find this acceptable. Complication and hospitalization rates were low. The presence of residual renal function often allows complications to be managed without the need for hemodialysis. The use of icodextrin as a single-exchange dialysate is associated with sterile peritonitis in a significant proportion of cases.

Adult↗
PubMed2005

Home peritoneal ultrafiltration in patients with severe congestive heart failure without end-stage renal disease.

Congestive heart failure (CHF), mainly because of ischemic heart disease, is becoming a common medical problem. As CHF worsens and reaches New York Heart Association (NYHA) class IV, many patients can become refractory to medical therapy, especially those who are elderly or who have pre-existing non uremic chronic renal failure. For such patients, quality of life, morbidity, and mortality are expected to be bad. Our objective in the present study was to make a preliminary assessment of the usefulness of icodextrin administered in a single nocturnal peritoneal exchange to patients nonrespondent to the maximal conventional medical therapy. We studied two patients (aged 80 and 87 years), who were affected by severe dilatative cardiomyopathy and moderate-to-severe chronic renal failure. After at least 12 months of treatment, we observed a significant improvement in quality of life and a reduction in morbidity and hospitalization in both patients. Both patients also significantly increased their creatinine clearance. One patient maintained ejection fraction stability (22%-->27%); the other experienced an increase in ejection fraction to 50%from 25%. These preliminary observations suggest that a single nocturnal exchange with icodextrin can be an effective treatment in patients affected by refractory CHF and moderate-to-severe chronic renal failure.

Aged, 80 and over↗
PubMed2006

[Hypoglycaemic coma due to falsely elevated glucose values in a patient with diabetes mellitus and peritoneal dialysis].

A 45-year-old female diabetes-mellitus patient on peritoneal dialysis was admitted because of vertigo. During her stay in hospital she developed a comatose condition with abnormal head posture and deviation ofthe eyes to the left. Capillary blood from the fingertip showed a glucose value of 15.4 mmol/l. However, the automatically obtained glucose value delivered with a blood-gas analysis was found to be 1.2 mmol/l. The neurological state of the patient normalised fully after intravenous glucose administration. The glucose values were falsely elevated because the patient used a peritoneal dialysis fluid at night which contained icodextrin as an osmotic agent. Metabolites of icodextrin can influence blood-glucose measurements taken using analyzers that depend on the enzyme glucose dehydrogenase. To prevent potentially life-threatening situations, the use of an adequate glucose meter is of paramount importance.

Autoanalysis↗
PubMed1996

Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier solution.

A novel peritoneal carrier solution, Icodextrin 20 (7.5%), has allowed exploration of prolonged, intraperitoneal (i.p.) infusion of the cytotoxic drug 5-fluorouracil (5-FU). A phase I and pharmacokinetic study was performed to determine the toxicities and maximum tolerated dose of prolonged and continuous intraperitoneal 5-FU in patients with peritoneal carcinomatosis. Seventeen patients were entered into this study. Each patient had a Tenckhoff catheter placed into the peritoneal cavity under general anaesthetic. After initial flushing and gradual increase in exchange volumes with Icodextrin 20, 5-FU was administered daily from Monday to Friday, 50% as a bolus in the exchange bag and 50% in an elastomeric infusor device delivering continuous 5-FU to the peritoneal cavity at 2 ml h-1. Treatment was continued for 12 weeks or until intolerable toxicity developed. Abdominal pain and infective peritonitis proved to be the main dose-limiting toxicities. Initial problems with infective peritonitis were overcome by redesign of the delivery system, and it proved possible to deliver 300 mg m-2 5-FU daily (5 days per week) for 12 weeks. Pharmacokinetic studies showed i.p. steady-state 5-FU concentrations (mean 47 500 ng ml-1) that were > 1000-fold higher than systemic venous levels (mean 30 ng ml-1).

Adult↗
PubMed1997

Longitudinal follow-up of CA125 in peritoneal effluent.

Mesothelial changes occur during peritoneal dialysis. CA125 provides a way to study the mesothelial cells in the in vivo situation. In the present study longitudinal changes of CA125 were analyzed. In addition, the appearance of CA125 in peritoneal effluent and day-to-day variability were studied. CA125 was measured in the effluent of five stable CAPD patients during four hour dwells with 1.36% glucose, with 3.86% glucose and with 7.5% icodextrin. In addition, CA125 was determined on six consecutive days in four hour effluents of three patients and appearance rates (AR) were calculated. Longitudinal follow-up was performed in 31 patients in whom three to seven yearly observations had been made. Linear appearance of CA125 was present in all dwells. No difference was found between the appearance rates of CA125 with 3.86% glucose, compared to either 1.36% glucose or icodextrin. Mean day-to-day coefficient of variation was 6.4% for CA125 AR, but a wide variation existed in stable CA125 values among patients (mean 22.1, range 2 to 48 U/ml). A negative trend with duration of CAPD was present in the longitudinal study. A mean decrease of 2.2% per year could be calculated, but substantial interindividual differences existed. Sudden decreases of CA125 AR were found in five patients. Possible causes were found in all of them and included a severe or recurrent peritonitis, and temporary cessation of peritoneal dialysis. In one patient a sudden decrease preceded the manifestation of peritoneal sclerosis. It can be concluded that CA125 can be used for the in vivo follow-up of the mesothelium in peritoneal dialysis patients. The appearance of CA125 in effluent is linear in time and not influenced by the initial lysis of mesothelial cells. A gradual loss of mesothelial cells is likely to occur, although interindividual variability is substantial. An acceleration of the process may be caused by severe peritonitis and perhaps by temporary cessation of peritoneal dialysis. A sudden decrease in CA125 may be an alarming sign for the development or manifestation of peritoneal sclerosis.

CA-125 Antigen↗
PubMed2006

Mitigating peritoneal membrane characteristics in modern peritoneal dialysis therapy.

Membrane function at the start of peritoneal dialysis (PD) treatment, measured as solute transport rate and ultrafiltration capacity, varies considerably between individuals. Although this can be correlated to clinical factors such as age and body habitus, this accounts for little of the variance seen. It is increasingly clear, however, that this variability in membrane function does impact on clinical outcomes. Specifically, high solute transport increases mortality risk, independent of other known factors such as age, comorbidity, and residual renal function. High solute transport causes earlier loss of the osmotic gradient when a low molecular weight osmolyte such as glucose is used. This will result in an earlier and lower peak in the ultrafiltration achieved combined with a higher fluid absorption rate once the osmotic gradient is lost. It is therefore quite plausible that the worse clinical outcomes associated with high transport reflect less good ultrafiltration, although other explanations must be considered, including higher peritoneal protein losses and a possible association with systemic inflammation. Strategies now exist to mitigate the effects of high transport on fluid removal. These include optimization of the short dwell lengths using automated PD (APD) combined with icodextrin which will result in sustained ultrafiltration and thus prevention of reabsorption in the long dwell. Survival analysis of APD patients, especially in cohorts in which icodextrin has been used, would suggest that high transport status is not a risk factor, although some of these data are only preliminary. In contrast, low ultrafiltration capacity of the membrane seems to be more important in these patients, especially if anuric. Here the best strategy would seem to be prevention as patients who develop low ultrafiltration capacity are not easily treated on PD. Avoiding excessive hypertonic glucose exposure and preserving residual renal function offers the best available approach.

Dialysis Solutions↗
PubMed2001

Acute effects of peritoneal dialysis solutions on appetite in non-uremic rats.

BACKGROUND: Standard peritoneal dialysis (PD) solutions may contribute to anorexia in PD patients due to the peritoneal absorption of glucose from the dialysate, abdominal discomfort and other factors. New PD solutions containing alternative osmotic agents, neutral pH and bicarbonate as buffer were recently developed. To test the effect of these solutions on appetite, we investigated how intraoral (IO) intake of sucrose via an IO cannula was influenced by intraperitoneal (IP) infusion of different PD solutions in an appetite model in rats. METHODS: The IO intake was measured in male Wistar rats after an IP dwell of 30 and 120 minutes with the following PD solutions: 1.36%, 2.27% and 3.86% glucose based and lactate buffered solutions (D); 1.36%, 2.27% and 3.86% glucose based and bicarbonate/lactate buffered solutions (P); 7.5% icodextrin based solution (E); 1.1% amino acid-based solution (N); and, 2.5% glucose-based lactate-buffered solution (GB), using sham injection (injection without infusion) as control. Prior to the tests, rats were provided with an IO cannula, and were trained for two weeks until the rate of IO intake had stabilized. RESULTS: The D and N solutions inhibited IO intake. For the D solutions, the degree of appetite suppression was higher with the higher concentration of glucose. P 3.86%, but not P 1.36% and P 2.27% solutions, inhibited the IO intake. However, a comparison of the degree of appetite inhibition between D and P showed less inhibition with P 1.36%, 2.27% and 3.86% solutions than with corresponding D solutions. The E solution did not seem to suppress appetite. Finally, no significant difference in IO intake was found between rats given GB 2.5% and D 2.27%. CONCLUSIONS: In this appetite model in rats, the measurement of IO intake after the IP infusion of different dialysis solutions showed that (1) N and D solutions may reduce appetite, and for the D solutions the degree of appetite inhibition was related to the dialysate concentrations of glucose; (2) the P solutions had less impact on appetite than the D solutions; (3) the E solution had no impact on appetite during the short dwells of 30 and 120 minutes. The demonstrated differences between the different solutions appear to be due to different concentrations, and type, of nutrients used as osmotic agent (glucose, amino acids, icodextrin) or buffer (lactate), although differences in dialysate pH, tonicity and concentration of glucose degradation products also may be important. The present studies suggest a possible positive effect on appetite by using bicarbonate/lactate buffered solutions instead of lactate buffered solutions.

Administration, Oral↗
PubMed2005

Do interleukin-6, hyaluronan, soluble intercellular adhesion molecule-1 and cancer antigen 125 in dialysate predict changes in peritoneal function? A 1-year follow-up study.

OBJECTIVE: Diminishing ultrafiltration and dialysis adequacy may limit the long-term use of peritoneal dialysis (PD). Inflammation may play a role in changes in peritoneal function. This study was designed to evaluate alterations in peritoneal function and soluble factors in dialysate during a 1-year follow-up period. MATERIAL AND METHODS: A personal dialysis capacity test was performed at the start of the study and after 6 and 12 months in 20 patients in order to determine dialysis adequacy and membrane characteristics. Dialysate was collected during the test days for analyses of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, hyaluronan and cancer antigen 125 (CA125). RESULTS: There were no significant changes in dialysis adequacy or membrane characteristics during the 1-year follow-up period. The appearance rate of IL-6 in dialysate increased significantly (419.8+/-63.3 at the start, 784.1+/-136.4 after 6 months and 1149.3+/-252.2 ng/24 h after 12 months; p=0.006) during follow-up. Furthermore, the appearance rate of CA125 increased throughout the study in patients using icodextrin, but decreased slightly in patients using only conventional dialysis solutions. CONCLUSIONS: There were no major changes in dialysis adequacy or membrane characteristics during the follow-up period, but increased IL-6 in dialysate may reflect peritoneal inflammation, which may lead to long-term alterations in the peritoneal membrane. Icodextrin may have a preventive effect on the longevity of the peritoneal membrane.

Adult↗
PubMed2005

Evaluation of peritoneal transport properties at onset of peritoneal dialysis and longitudinal follow-up.

BACKGROUND: The clinical determinants of baseline peritoneal membrane (PM) transport characteristics, as evaluated by a hypertonic peritoneal equilibration test (PET), remain ill-defined. Likewise, the longitudinal evolution of PM transport properties in peritoneal dialysis (PD) patients given automated PD (APD) and icodextrin still needs to be determined precisely. The aims of the present study were (1) to determine the clinical and biological factors affecting PM transport characteristics at PD onset and (2) to assess the longitudinal evolution of these markers. METHODS: Seventy-two consecutive patients performed a baseline 3.86% glucose dialysate PET and were enrolled. Subgroups of 35 and 18 patients underwent another PET 1 and 2 year(s) later, respectively, and were included in the longitudinal part. For each patient, clinical and biological data were reviewed and PM transport markers calculated. RESULTS: At onset of PD, angiotensin-converting enzyme (ACE) inhibitor intake (r = 0.31, P = 0.01), presence of a diabetes (r = 0.26, P = 0.03) and body surface area (BSA) (r = 0.26, P = 0.03) independently affected the mass transfer area coefficient (MTAC) of creatinine. Serum albumin (r = -0.46, P<0.001) and net ultrafiltration (r = -0.33, P = 0.009) inversely correlated with MTAC creatinine. Sodium sieving was inversely correlated with BSA (r = -0.33, P = 0.01). Serum albumin also inversely correlated with albumin clearance (r = -0.39, P = 0.02). Finally, the independent covariates that affected alpha2-macroglobulin clearance were age (P = 0.03), diabetes (P = 0.01) and the level of residual renal function (P<0.01). Serum albumin decreased with time on PD (P = 0.02). A rise in small solute transport and a decrease in net ultrafiltration, but no change in protein clearances, were also observed after 2 years of PD. CONCLUSIONS: Transport properties across the PM, as evaluated by MTAC creatinine and sodium sieving determinations, are correlated with anthropometric characteristics (BSA) and by comorbid conditions (witnessed by the presence of diabetes, a low serum albumin concentration and the prescription of an ACE inhibitor). The short-term evolution (2 years) of the PM transport properties of patients on APD and icodextrin is still characterized by a progressive increase in small solute transport and a loss of ultrafiltration capacity, as documented in ancient studies, but not with a modification in protein clearances. This conclusion merits, however, to be further evaluated in a larger cohort of PD patients after a longer follow-up.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Effects of new peritoneal dialysis solutions on leukocyte recruitment in the rat peritoneal membrane.

OBJECTIVES: Peritonitis remains a principal cause of dropout in peritoneal dialysis (PD). The physiological host response to a peritoneal infection involves a rise in numbers of circulating leukocytes to the peritoneal cavity. We evaluated the effects of (1) conventional peritoneal dialysis fluid (PDF), (2) bicarbonate-based PDF, low in glucose degradation products, and (3) non-glucose PDF on peritoneal leukocyte recruitment in response to an inflammatory stimulus using intravital microscopy. METHODS: The visceral peritoneum was exposed to EBSS, conventional lactate-buffered and bicarbonate/lactate-buffered glucose-based PDF and three lactate-buffered non-glucose PDF-icodextrin, amino acid-based PDF and amino acid/glycerol-based PDF. The number of rolling, adhering and extravasated leukocytes and leukocyte rolling velocity was assessed at different time intervals after stimulation with lipopolysaccharide (LPS). RESULTS: Exposure to LPS dissolved in EBSS dramatically increased the number of rolling, adhering and extravasated leukocytes and decreased leukocyte rolling velocity. Conventional PDF completely abolished LPS-induced leukocyte recruitment. Bicarbonate/lactate-buffered PDF only minimally affected the process of leukocyte recruitment, whereas icodextrin PDF resulted in partial inhibition of the immune response. The amino acid-based and the amino acid/glycerol-based PDF inhibited leukocyte recruitment to a similar extent as conventional PDF. CONCLUSIONS: Bicarbonate/lactate-buffered PDF has superior biocompatibility towards peritoneal host defense, in spite of its high glucose concentrations. Lactate-buffered non-glucose containing PDF has substantial inhibitory effects on leukocyte recruitment, indicating that the bioincompatibility of high lactate concentrations and/or low pH may not be underestimated.

Amino Acids↗
PubMed2006

Repopulation of the mesothelial monolayer during long-term experimental peritoneal dialysis.

BACKGROUND: Repopulation of the mesothelial monolayer after focal exfoliation, having the monolayer in vivo and in situ exposed to dialysis solutions, has not been thoroughly investigated. This study describes repopulation of a 'doughnut' like mesothelial ring exfoliated from the anterior liver surface of rats. METHODS: Animals were divided into 5 groups of 20 rats each. Group 1 - control unexposed animals: mesothelial cell imprints were taken after 1 (5 rats), 5 (5 rats), and 15 (10 rats) days following the procedure of exfoliation. Group 2 - sham injected animals. Group 3 - rats IP injected once a day, during 30 consecutive days with Hank's balanced salt solution. Groups 4 and 5 - same experimental protocol, but injecting 4.25% glucose single bag or 7.5% Icodextrin PDF. Imprints and/or biopsies were taken after a recovery period of 15 days, counted from the last IP injection. RESULTS: Density distribution of mesothelial cells in group 2 was not significantly different from that seen in unexposed rats, whereas that seen in group 3 Hank's balanced salt solution was marginally but significantly lower (p < 0.05) from that seen in controls. Eighty five percent of rats injected with 4.25% glucose developed fibrous adhesions, binding up together the exfoliated liver surface and the diaphragmatic muscle. For Icodextrin treated rats, the prevalence of fibrous adhesions was 95%. CONCLUSIONS: The 'doughnut' experimental model appears as a promising tool for in vivo and in situ investigation of mesothelial repopulation. Both osmotic agents substantially restrain mesothelial repopulation, leading to repair by connective tissue.

Animals↗
PubMed2005

Prevention of peritoneal sclerosis: a new proposal to substitute glucose with carnitine dialysis solution (biocompatibility testing in vitro and in rabbits).

AIM: Commercial glucose peritoneal dialysis solutions expose the peritoneum to hyperosmolar glucose containing variable amounts of non-enzymic breakdown products of glucose. These solutions are toxic for the peritoneum. The aim of the present study is to compare in vitro and in vivo characteristics of a new dialysis solution containing carnitine, a naturally occurring compound, as substitute of glucose. MATERIAL AND METHODS: We compared in vitro and in the rabbit a new peritoneal dialysis solution containing carnitine, with two standard bicarbonate glucose peritoneal dialysis solutions and a solution containing icodextrin. RESULTS: In vitro and in vivo the solution containing carnitine seems to be more biocompatible than standard glucose solutions and those containing icodextrin. CONCLUSIONS: In our study the peritoneal dialysis solution containing carnitine seems to prevent the mesothelial changes observed with solutions containing glucose. Since carnitine has been extensively studied and seems to be well tolerated by hemodialysis patients, even at high doses for long periods, clinical trials in humans may be planned in the near future.

Animals↗
PubMed2000

Strategies to reduce glucose exposure in peritoneal dialysis patients.

Glucose has been used successfully for more than two decades in peritoneal dialysis, and in this regard, must be considered a safe and effective osmotic agent. Recently, however, insight has been growing about the potential for metabolic and peritoneal effects arising from long-term exposure to high glucose concentrations--for example, hyperlipidemia and loss of peritoneal ultrafiltration. Clinical concerns over exposure to excessive glucose and glucose degradation products (GDPs) during peritoneal dialysis can be significantly ameliorated by the use of non-glucose-based peritoneal dialysis (PD) solutions, in combination with more biocompatible glucose-based formulations. Peritoneal exposure to GDPs can be reduced by using low-GDP-containing glucose formulations and non glucose solutions such as amino acids and icodextrin. Peritoneal glucose exposure, hyperosmolar stress, and carbohydrate absorption can be reduced by using a combination of icodextrin and amino acids.

Absorption↗
PubMed2000

Effects of conventional and new peritoneal dialysis solutions on human peritoneal mesothelial cell viability and proliferation.

OBJECTIVE: To investigate the biocompatibility of "new" peritoneal dialysis (PD) solutions with bicarbonate/lactate buffer, non glucose osmotic agents (icodextrin or amino acids), neutral pH, and low levels of glucose degradation products (GDPs). DESIGN: Using M199 culture medium as a control, we compared conventional and new PD solutions with respect to their effects on the viability of human peritoneal mesothelial cells (HPMCs) [using lactate dehydrogenase (LDH) release], on DNA damage in HPMCs [using single-cell gel electrophoresis (Comet assay)], and on HPMC proliferation (using [3H]-thymidine incorporation). The experiments were performed after cell growth was synchronized by incubation with serum-free media for 24 hours. The PD solutions tested included commercial 1.5% glucose and 4.25% glucose solutions with 40 mmol/L lactate (D 1.5 and D 4.25, respectively), 7.5% icodextrin (E), 1.1% amino acid (N), 1.5% glucose solution in a triple-chambered bag (Bio 1.5), 1.5% glucose solution in a dual-chambered bag with neutral pH (Bal 1.5), and 1.5% glucose and 4.25% glucose solution containing 25 mmol/L bicarbonate and 15 mmol/L lactate (P 1.5 and P 4.25, respectively). RESULTS: When HPMCs were continuously exposed to undiluted PD solutions, D 1.5, D 4.25, P 4.25, and E increased LDH release by more than 60% at 24 hours. All PD solutions tested increased LDH release by more than 75% at 96 hours. With 2-fold diluted PD solutions, only D 4.25 significantly increased LDH release at 96 hours, though not at 24 hours. When cells were exposed to undiluted PD solutions for 60 min and allowed to recover in M199 for up to 96 hours, LDH release was significantly higher at 24-96 hours in E (55%-69%) and D 1.5 (48%-72%) as compared with control [M199 (18%)]. Release of LDH was significantly lower with PD solutions containing lower levels of GDPs than those in D 1.5, suggesting that GDPs may have a role in cell viability. The D solutions (D 1.5 and D 4.25) and E solution also induced significant DNA damage. Both LDH release and DNA damage by D and E were significantly attenuated by adjusting the solution pH to 7.4, suggesting that low pH may be implicated in PD solution-induced DNA damage and cell death. When diluted 2-fold, D 1.5, D 4.25, and P 4.25 decreased [3H]-thymidine incorporation to 43%, 34%, and 41% of control, respectively, at 24 hours and to 45%, 26%, and 35% of control, respectively, at 96 hours. When cells were exposed to undiluted PD solutions for 5 minutes and allowed to recover in M199 for up to 96 hours, D1.5 and P 4.25--but not D 4.25--significantly inhibited cell proliferation at 24 hours. This effect was sustained up to 96 hours. CONCLUSIONS: The present in vitro data demonstrate that PD solutions with low pH, or high levels of GDPs, or both, promote HPMC death and DNA damage, and that PD solutions with high osmolality inhibit cell proliferation. Solutions with neutral pH, amino acids, and "low GDPs" appear to be more biocompatible than conventional PD solutions. These results require confirmation in in vivo animal and clinical studies.

Cell Division↗
PubMedDate not supplied

[Improving the outcome of peritoneal dialysis in the long term: is it possible?].

Improving the results of peritoneal dialysis (PD) over time means reducing both the technique's drop out (TDO) and mortality rates. The PD mortality rate has diminished over the years, due to greater experience in using the technique and the reduction in mortality due to peritonitis making it comparable with the hemodialysis (HD) mortality rate. Moreover, improved control of the hydrosaline balance through the use of ambulatory peritoneal dialysis (APD) and icodextrin could further improve the survival rate in the future. The adequacy targets needed to reduce the mortality rate still appear to be debatable, as their importance seems conditioned by the presence of RRF and comorbidity. The TDO is higher in PD than in HD because PD is a self-administered treatment that uses a biological membrane as a filter. The most frequent causes of TDO are peritonitis (30-40%), dialytic inadequacy (11-27%), and subsequent inability and/or choice (10-32%). Peritonitis is the cause that has seen the greatest reduction over time due to the introduction of the Y-Set, but a further reduction could result from the prevention of ESI, and from improvements in the patient selection procedure designed to identify both clinical and psycho-social disposition peritonitis risk factors. Among the causes of TDO due to dialytic inadequacy, insufficient ultrafiltration (UF) could benefit from the diffusion of APD and icodextrin, while insufficient depuration could be reduced by new targets and optimization of the prescription. Finally, TDO due to social causes could be reduced by the use of APD, care support and appropriate patient selection.

Humans↗
PubMedDate not supplied

[Sodium kinetics in peritoneal dialysis: from theory to clinical practice].

Cardiovascular disease (CVD) is the leading cause of death in dialysis patients. Among the main risk factors for CV mortality, hydro-saline retention is frequently observed in peritoneal dialysis (PD) patients, due to the transport mechanisms occurring within the peritoneal cavity. The analysis of sodium (Na) kinetics is a useful method to understand better the transport of fluids and solutes in PD. In the absence of peritoneal ultrafiltration (UF), Na removal by diffusion during a peritoneal dwell is extremely low. Therefore, to increase peritoneal Na removal, the attainment of peritoneal UF is a basic requisite; however, achieving this goal requires the use of solutions with hypertonic glucose concentrations. On the other hand, such a type of convective transport induces the transport of free-water, by aquaporin-1 channels located on the endothelial side of the peritoneal membrane; therefore, leading to a disproportionate removal of plasmatic water as compared with the removal of plasmatic Na (hyponatric removal). PD solutions containing icodextrin at 7.5% concentration determine UF with a different mechanism (colloid-osmotic), without inducing any free-water transport. However, clinical studies have failed to show a benefit of icodextrin solution in reducing blood pressure (BP) values and increasing Na removal. Therefore, the use of PD solutions with low Na concentrations (102-120 mmol/L) has been recently proposed as another available therapeutic strategy to prevent the development and reduce the prevalence of hydro-saline retention and hypertension in PD patients.

Dialysis Solutions↗