Is long-term technique survival on continuous ambulatory peritoneal dialysis possible?
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Biomedical subjects
Publications and source records attributed to D G Oreopoulos.
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OBJECTIVE: Some patients develop a mild acidemia during treatment with amino acid-based peritoneal dialysis solutions due to hydrogen ion produced by metabolism of lysine, arginine, and methionine. In this study we modified the formulation of such a solution by reducing these amino acids and adding anionic amino acids so as to provide minimal net acid production. DESIGN: A modified formula (MF) was compared to a conventional formula (CF) of the solution in a randomized cross-over study in 12 stable continuous ambulatory peritoneal dialysis patients. Patients were given each solution for 14 days without a wash-out period. Each patient replaced one or two dextrose dialysis exchanges with amino acid solution, depending upon oral protein intake and body weight. Total intake (oral protein plus amino acids absorbed) was equivalent to 1.1-1.3 g protein/kg body weight/day. Plasma bicarbonate and urea were assessed at the beginning and end of each 14-day period. RESULTS: In the group as a whole, without regard to the order in which the solutions were given, patients had a decrease in serum bicarbonate with CF and an increase in bicarbonate when they received MF. Similar trends were observed regardless of the order in which the solutions were administered. Serum urea did not differ between the two solutions. CONCLUSION: The results suggest that patients are less prone to develop acidemia when receiving MF as opposed to CF. Further studies will be necessary to determine the long-term effects and the relative nutritional benefits of the two solutions.
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OBJECTIVES: The purpose of this study was to investigate the effects of acute peritonitis on lymphatic drainage of the peritoneal cavity in conscious sheep. DESIGN: Peritonitis was induced with the addition of 1% casein or 1% albumin to the dialysis solution. Thirty sheep (5 groups of 6) were used in this study. One group received 50 mL/kg intraperitoneal infusions of Dianeal 4.25% (486 mOsm/L); a second group received 1% casein-Dianeal 4.25% (493 mOsm/L); a third group received 1% albumin-Dianeal 4.25% (487 mOsm/L). In the fourth and fifth groups (controls and casein-injected) lymph was collected from the caudal mediastinal lymph node and the thoracic duct, both of which are involved in the lymphatic drainage of the peritoneal cavity (peritonitis induced with casein). (125)I-human serum albumin (25 mu CI) was added to the dialysate as the lymph flow marker. Lymph drainage was estimated from (1) the appearance of the intraperitoneally administered tracer in the blood; (2) the disappearance of the tracer from the peritoneal cavity; and (3) the recovery of tracer in lymph. RESULTS: In noncannulated animals the cumulative volume removed by lymphatics over 6 hours (based on tracer recovery in blood) was 10.5 +/- 1.0 mL/kg in control animals versus 5.0 +/- 0.6 mL/kg and 8.6 +/- 1.2 mL/kg in casein and albumin-infused sheep, respectively. The suggestion of decreased lymph drainage in peritonitis was supported by the cannulation experiments. While the cumulative fluid removed from the peritoneal cavity over 6 hours in caudal lymph was unaffected by peritonitis (3.8 +/- 0.4 mL/kg in controls vs 3.6 +/- 0.5 mL/kg in casein-injected animals), peritonitis reduced flow into the thoracic duct from 3.0 +/- 0.3 to 1.1 +/- 0.3 mL/kg. The sum of the volume removed in lymph in the cannulated preparations was 6.8 +/- 0.4 mL/kg in controls versus 4.7 +/- 0.5 mL/kg in the peritonitis group. The total volume removed from the cavity (including an estimate of flow based on the residual recovery of tracer in blood) was reduced from 12.6 +/- 1.4 in controls to 7.8 +/- 0.6 mL/kg in the peritonitis sheep. In contrast, estimates of lymph drainage based on the disappearance of tracer from the peritoneal cavity suggested that lymph drainage increased (from 16.6 +/- 1.6 mL/kg in controls to 17.8 +/- 1.5 mL/kg and 25.5 +/- 1.7 mL/kg in the casein and albumin groups, respectively, in noncannulated animals and from 15.3 +/- 1.4 mL/kg in controls to 25.0 +/-1.7 mL/kg in the cannulated group). In both noncannulated and cannulated sheep the total recovery of tracer was less in the peritonitis groups. CONCLUSIONS: These studies demonstrated that lymph drainage of the peritoneal space was decreased in a casein peritonitis model. The decrease in lymph drainage is most obvious in the visceral pathway leading to the thoracic duct; however, diaphragmatic drainage into the right lymph duct may also be inhibited. The disappearance of tracer from the peritoneal cavity was elevated during peritonitis. Tracer disappearance has been used to estimate lymph drainage, but this approach suggested, incorrectly, that lymph flow had increased.
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OBJECTIVE: To assess the effect of insulin on the Na+/K(+)-ATPase expression and activity in human peritoneal mesothelial cells (HPMC). METHODS: HPMC were isolated from the omental tissue of non-uremic patients, grown to confluence and rendered quiescent by serum deprivation for 24 hours. The activity of Na+/K(+)-ATPase was determined by measuring the ouabain-sensitive 86Rb uptake. To assess whether the effect of insulin was related to changes in [Na+]i the sodium influx was measured with 22Na and the activity of Na+/K(+)-ATPase was assessed in the presence of amiloride. Expression of Na+/K(+)-ATPase alpha 1,alpha 2 and beta 1-subunit mRNAs was determined by RT/PCR. RESULTS: Exposure of HPMC to insulin resulted in a time- and dose-dependent increase in the Na+/K(+)-ATPase activity. After 60 minutes the ouabain-sensitive 86Rb uptake (cpm/10(4) cells) was increased from 6650 +/- 796 in control cells to 9763 +/- 1212 in HPMC exposed to 100 mU/mL insulin (1.5-fold increase; n = 4, P < 0.05). In addition, incubation of HPMC with 100 mU/mL insulin resulted in a time-dependent increase in the 22Na influx. Pre-exposure of HPMC to 1mM amiloride reduced the activity of Na+/K(+)-ATPase but did not block the stimulatory effect of insulin. RT/PCR analysis revealed that HPMC constitutively expressed alpha 1- and beta 1-subunit mRNAs while the alpha 2-subunit mRNA was barely detectable. Exposure of HPMC to insulin for up to 24 hours was not associated with any changes in the expression of either alpha 1, alpha 2 or beta 1-subunit. CONCLUSION: Insulin stimulates the Na+/K(+)-ATPase activity in HPMC in a time- and dose-dependent manner. This effect appears to mediated by an increase in [Na+]i and is not related to alterations in Na+/K(+)-ATPase subunit mRNAs expression.
OBJECTIVE: Evaluation of peritoneal surface area and its permeability during dialysis in rats of various ages. DESIGN: Study I: planimetry of peritoneum and its topographic areas was performed in 47 rats of various ages (8-30 weeks). Study II: net ultrafiltration (UF), dialysate-to-serum ratios for urea, creatinine, albumin, and total protein as well as their peritoneal permeability coefficients, were measured during a 1-hour peritoneal exchange with Dianeal 2.5%, in 21 rats of different ages (9-30 weeks) and with various peritoneal surface areas. ANIMALS: Male Wistar rats. RESULTS: The peritoneal surface area in rats increases during aging, but young animals with lower body weight have a relatively larger peritoneal surface area than older, larger animals. The area of the topographic fragments of peritoneum expressed as a percentage of the total peritoneal surface is steady during aging. Efficiency of transperitoneal water removal expressed as net UF per amount of absorbed glucose declines in older animals, with larger peritoneal surface areas. Dialysate/serum ratio of solutes transported from blood to dialysate is proportional to peritoneal surface area. Permeability coefficient (K) of peritoneum to urea and creatinine is unchanged during the aging of animals. However peritoneal permeability (K) to albumin increases during aging, with the opposite tendency for total proteins. CONCLUSIONS: Kinetics of peritoneal dialysis in rats of different ages is determined by peritoneal surface area and permeability of peritoneum to individual solutes.
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OBJECTIVE: To assess the effect of an inhibitor of nitric oxide synthesis [N(G)-nitro-L-arginine methyl ester (L-NAME)] on peritoneal transport during peritoneal dialysis (PD) and peritonitis in rats. METHODS: The authors studied peritoneal transport of small and large solutes, and net ultrafiltration (UF) in rats during PD with Dianeal 3.86 (Baxter, McGaw Park, IL, U.S.A.). They evaluated the effect of L-NAME used as an additive to dialysis fluid in concentrations 0.5-5 mg/mL on peritoneal transport of small and large molecules and on transperitoneal UF. In addition, they studied the effect of L-NAME (5 mg/mL) during acute peritonitis induced by lipopolysaccharides (5 microg/mL) given intraperitoneally. RESULTS: The addition of L-NAME to dialysis fluid increased the selectivity of the peritoneum and net UF during dialysis. Lipopolysaccharides used as an additive to the dialysis fluid, together with L-NAME, did not induce changes in transperitoneal transport of small and large solutes and did not cause a significant decline in net UF. L-NAME given intraperitoneally reduced both local and systemic production of nitric oxide, which might explain its effects on peritoneal transport. CONCLUSIONS: Nitric oxide is an important mediator of changes in peritoneal transport and its effect is especially significant during peritonitis.
OBJECTIVE: To evaluate the potential effectiveness of the application of mupirocin ointment at the catheter exit site in preventing exit-site infection and peritonitis caused by Staphylococcus aureus (SA). DESIGN: This prospective, historically controlled study was done on 181 peritoneal dialysis patients treated between 1 November 1996 and 1 November 1997. They were instructed to apply mupirocin at the catheter exit site daily or three times per week at the conclusion of their exit-site care (Study 1). The patients were not screened to determine whether they were SA carriers. The group's historical control was the infection data from the previous year among these patients. A second group of 70 patients, who started using mupirocin within a month after catheter implantation (1996-1997), was compared with a historical group of 118 patients (controls) who were on continuous ambulatory peritoneal dialysis (CAPD) for 1 year after in-patient implantation without mupirocin, (1990-1995) (Study 2). RESULTS: In the group of 181 patients (Study 1), application of mupirocin at the exit site led to a significant reduction in SA exit-site infections--21 versus 3 episodes (0.11 vs 0.01 episodes/patient/year)--and a significant reduction of SA peritonitis--35 episodes in the year preceding mupirocin versus 11 episodes during the year of mupirocin treatment (0.19 vs 0.06 ep/pt/yr). The same results were observed in Study 2: the incidence of SA exit-site infection was significantly lower in the mupirocin-treated group--17 episodes among the 118 nontreated patients versus 4 episodes among 70 patients using mupirocin (0.14 ep/pt/yr vs 0.06 ep/pt/yr, respectively). Similarly there were 20 episodes of SA peritonitis among 118 patients during their first year of CAPD versus 4 episodes in 70 mupirocin-treated patients (0.16 ep/pt/yr vs 0.06 ep/pt/yr, respectively). No adverse effects were observed among the patients treated with mupirocin. Overall peritonitis rates decreased from 0.87 to 0.48 ep/pt/yr (p < 0.01) in Study 1 and from 0.56 to 0.41 ep/pt/yr (p = NS) in Study 2. We observed no differences in the incidence of exit-site infection and peritonitis rates among patients applying mupirocin ointment at the exit site daily, compared to three times per week. CONCLUSIONS: Mupirocin application at the exit site significantly lowers the incidence of SA exit-site infections and peritonitis due to SA infections. Since SA infections are accompanied by significant morbidity and occasional mortality, this treatment may improve long-term survival of patients on CAPD.
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OBJECTIVE: To evaluate the potential effectiveness of nystatin as prophylaxis for fungal peritonitis (FP) in patients on continuous ambulatory peritoneal dialysis (CAPD). DESIGN: This historically controlled study was designed to investigate the effectiveness of nystatin in the prevention of FP. For this purpose we compared the incidence of FP among 240 (new and prevalent) CAPD patients between January 1996 and November 1996 (period A) with its incidence in 240 new and prevalent CAPD patients in our program between January 1997 and November 1997 (period B) when nystatin prophylaxis was used. There were 2400 patient-months in each period. Nystatin (500,000 IU four times per day), was given orally at the beginning of other antibiotic therapy (usually for peritonitis) and continued for 5 days after the end of the antibiotic therapy. RESULTS: During period A, 133 peritonitis episodes were recorded, and during period B, 99 episodes were recorded. Six episodes of FP were identified in over 2400 patient-months of period A, and 12 in over 2400 patient-months of period B. This difference was not statistically significant. Three episodes of antibiotic-related FP were seen in period A, and four in period B. The remaining episodes arose de novo, that is, unrelated to the use of antibiotics. We observed no side effects for nystatin. CONCLUSION: In CAPD patients the use of nystatin, a nonabsorbable antifungal agent, as prophylaxis in every instance of peritonitis or other indications for antibiotics, did not lower the incidence of fungal peritonitis.
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