Making long-term peritoneal dialysis possible.
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Biomedical subjects
Publications and source records attributed to D G Oreopoulos.
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We studied the effectiveness of CAPD in large patients (> 80 kg) (group B, n = 49) by comparing them to a group of patients whose body weight was 60-80 kg (group A, n = 193). Patients in group B were two years younger (55.4 versus 57.7 years, p < 0.01), were predominantly male (M: F ratio 33/16 vs 84/109) and had slightly higher residual creatinine clearance (8 ml/min vs 6 ml/min) at the beginning of treatment. The prevalence of diabetes and the prevalence of comorbid conditions in the two groups were similar. The incidence of peritonitis was similar between the two groups. Patients with a large weight spent significantly fewer days in hospital (20.6 +/- 25 vs 23.4 +/- 35.0 days/year); reasons for hospitalization were similar, except for weakness/fatigue that was more frequent (10%) in group B than in group A (2%). The initial weekly dialysate volume was similar in the two groups (57 +/- 51 in group B and 56 +/- 101 in group A) and increased in both groups at the end of the study to 60 +/- 141 in group B and 61 +/- 171/week in group A. The weight of 6 patients in group B and 5 in group A decreased below the range of that group. On the contrary the weight of 28 patients in group A increased to the range of group B. Based on the final weight there were 166 patients whose weight was 60-80 kg, and 71 patients whose weight was over 80 kg (80-109 kg). Patient survival was similar between the two groups. There was a significantly higher death rate among those patients whose weight decreased in both groups compared to those whose weight increased or remained stable. We conclude that CAPD is an effective treatment in the management of ESRD patients with weights over 80 kg. There is a high mortality among patients whose weight decreases irrespective of their initial weight.
Stepwise logistic regression performed in 324 clearance studies in 194 patients identified daily drain volume normalized by body water (DV/V) and peritoneal solute transport type as the predictors of peritoneal creatinine clearance (CCrp) in continuous ambulatory peritoneal dialysis (CAPD). Solution of the regression model for DV/V provided DV/V values predicted to provide a desired CCrp at different probabilities. The ability of the predicted DV/V to detect desired CCrp values was tested in a new set of 359 clearance studies in 217 CAPD patients who had a peritoneal equilibration test within 12 months of the clearance study. No patient with low transport had a CCrp exceeding 54 L/1.73 m2 weekly. The following DV/V values detected CCr > or = 54 L/1.73 m2 weekly with a probability of at least 80%: for low-average transport, 0.406 L/L per 24 hours; for high-average transport, 0.339 L/L per 24 hours; for high transport, 0.241 L/L per 24 hours. Corresponding DV/V values for a CCrp of 60 L/1.73 m2 weekly were as follows: for high-average transport, 0.351 L/L per 24 hours; for high transport, 0.271 L/L per 24 hours. For high-average transport, maximal body surface area (BSA) estimates allowing a CCrp of 60 L/1.73 m2 weekly at a CAPD schedule of four daily exchanges with 3-L exchange volume and 1.5 L/24 hour ultrafiltration volume, and with the specified DV/V values were 2.03 m2 in women and 1.77 m2 in men. Corresponding BSA estimates for high peritoneal solute transport were 2.58 m2 in women and 2.21 m2 in men. The delivered dose of CAPD, expressed as DV/V, required to achieve a target CCrp can be calculated from multivariate statistical models taking into account the peritoneal solute transport type. Multiplication of the required DV/V by V provides an estimate of the required daily exchange volume. Maximal BSA estimates allowing a target CCrp can be calculated for each gender and peritoneal solute transport type.
This study was designed to test the morphological and functional effects of neutral, bicarbonate-based peritoneal dialysis solution containing glycylglycine on the peritoneum of chronically dialyzed rats. Peritoneal dialysis catheters were implanted in 36 rats. The animals were dialyzed twice daily for 4 weeks with a solution containing bicarbonate (35 mmol/L), glycylglycine (10 mmol/L), and 4% of anhydrous glucose (pH 7.35) (group 1; n = 18) or with lactate-based standard 4.25% Dianeal (pH 5.3 (group 2; n = 18). At the beginning of the study, reabsorption of glucose was slower in group 1 (p < 0.02); at the same time, the hyaluronic acid level in the effluent was higher in this group (p < 0.05). However, towards the end of the study these differences disappeared. After 4 weeks of dialysis in rats exposed to bicarbonate-based solution only, the transperitoneal loss of proteins was slower. In morphological studies of the parietal peritoneum, we detected no statistically significant differences between control nondialyzed rats and those exposed to tested solutions. In a biopsy of visceral peritoneum a tendency was observed for increased thickness of peritoneum in rats dialyzed with both tested peritoneal dialysis solutions when compared to control animals. In conclusion, neutral pH glycylglycine peritoneal dialysis solutions seem to be more biocompatible than standard dialysis solutions.
The authors studied the effect of L-2-oxothiazolidine-carboxylate (OTZ), a substrate for intracellular glutathione synthesis, in an in vivo model of lipopolysaccharide (LPS)-induced peritonitis in rats. The addition of LPS to dialysis fluid increased the white blood cell (WBC) count and the nitrite (index of NO synthesis) level in the dialysate. The simultaneous addition of OTZ to the dialysis fluid prevented an increase of WBCs but not of nitrites in the dialysate. Intraperitoneal inflammation was accompanied by a decrease in net transperitoneal ultrafiltration, an increase in the absorption of glucose, and a loss of protein into the dialysate. OTZ partially reversed the effect of peritonitis on net ultrafiltration. Peritoneal leukocytes from rats exposed to LPS showed a reduced concentration of glutathione, an effect that was reversed in the presence of OTZ. These results show that the supplementation of dialysis fluid with OTZ modified the peritoneal reaction to acute inflammation.
This study was designed to analyze the complex morphologic and functional effects of dialysis solutions on peritoneum in a rat model on chronic peritoneal dialysis. Peritoneal catheters were inserted into 10 male, Wistar rats and the animals were dialyzed twice daily for 4 weeks with 4.25% Dianeal. During the study we observed two opposite effects: healing of the peritoneum after catheter implantation--decreased cell count in dialysate, decreased permeability of the peritoneum to glucose and total protein, increased volume of drained dialysate; and damage to the membrane due to its exposure to peritoneal dialysis solution--increased hyaluronic acid levels in dialysate, a tendency of the peritoneum to thicken when compared to non-dialyzed animals. Our rat model of CAPD may be used for quantitative and qualitative assessment of the effects of peritoneal dialysis solution on the peritoneum during chronic dialysis.
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L-2-Oxothiazolidine-4-carboxylate and N-acetylcysteine as substrates for intracellular glutathione in human peritoneal mesothelial cells were tested. Both substances at concentrations of 0.01 mM and higher augmented the level of glutathione in mesothelial cells. L-2-Oxothiazolidine-4-carboxylate had a milder but more stable effect than N-acetylcysteine. Cells with increased concentrations of the intracellular glutathione were more resistant to injury by free radicals. When used at higher concentrations (> 1 mM), both substances became cytostatic to mesothelial cells as evidenced by growth inhibition.
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Effect of peritoneal dialysis fluids on glutathione (GSH/GSSG) level in human peritoneal mesothelial cells was tested in in vitro experiments. To mimic in vivo conditions, cells were initially exposed to dialysis fluids (Dianeal 1.36%, Dianeal 2.27%, Dianeal 3.86%) that subsequently were diluted with dialysate effluent at time intervals. GSH/GSSG concentration in cells initially decreased but returned to normal values thereafter. This decrease in the intracellular concentration of glutathione was less when pH of the tested dialysis fluid was adjusted to 7.3. In further experiments with mesothelial cells exposed to Earle's salts solution supplemented with glucose and/or lactate, we have shown that in the presence of low pH, lactate is the main factor causing depletion of intracellular glutathione. When added to the dialysis solution at a concentration of 0.1 mM, L-2-oxothiazolidine-4-carboxylate, a precursor of glutathione, not only prevents the initial decrease in glutathione concentration but also augments the final intracellular level of this thiol.
Hypotension in patients on CAPD is almost an unexplored area in the literature. This retrospective analysis of 525 patients treated at the Toronto Hospital. Toronto over the last five years, of whom 65 were hypotensive, describes the possible causes of hypotension, the response to treatment, morbidity and mortality rates. The incidence of hypotension was 12% in our CAPD population. The mean age of these patients was 58 +/- 17 years with a male to female ratio of 1.25:1. The distribution of various comorbid conditions such as, insulin-dependent diabetes mellitus, neoplasia coronary/cerebro/peripheral vascular diseases was similar to nonhypotensive patients. There was a higher proportion of malignancies, noninsulin-dependent diabetes mellitus and chronic obstructive pulmonary disease (CAPD) in hypotensive group. Hypotension was attributed to hypovolemia in 16 (25%), heart failure in 15 (23%) and antihypertensive medications in 12 (18%) patients. In 26 (34%) patients the exact cause of hypotension was unclear. Five patients had malignancies and 4 had severe autonomic neuropathy. Among 16 hypovolemic patients, 14 responded to volume expansion and 2 did not because of concurrent administration of coronary vasodilators. Seven out of 12 patients with hypotension due to antihypertensive medications improved. In 3 patients, blood pressure increased marginally after stopping the drugs and 2 remained hypotensive because of continuation of the drugs. Of the patients with heart failure, 40% (6/15) responded to a decrease to the target weight. Two patients treated with captopril did not respond. Of the patients from the unknown category, 50% (13/26) improved. One out of 4 patients treated with midodrine responded. The mortality rate was higher among hypotensive patients than among the nonhypotensives on CAPD.
The liberalization of acceptance criteria for dialysis and the progressive increase of the elderly population overall have increased the number of elderly dialysis patients worldwide. The main underlying diseases leading to end stage renal disease (ESRD) in the elderly patients are hypertension and diabetes, but in many patients, the cause of renal disease is unknown. The principal form of renal replacement therapy (RRT) in the elderly is hospital hemodialysis. The 1995 annual report of the US Renal Data System (USRDS) indicated that from 1986 to 1990 for patients who were older than 65 years, the two major types of vascular access were arteriovenous fistula and synthetic polytetrafluoroethylene (PTFE) graft (more than 80% of the total). The elderly on hemodialysis have a higher rate of access morbidity, and, in them, the most common hemodialysis-related complications in the elderly are hypotension, arrthythmias, and gastrointestinal bleeding. Peritoneal dialysis is the only method that permits home treatment for most elderly people, the frequency of peritonitis and catheter-related complications are similar between young and elderly patients. Incidence of malnutrition increases significantly with age; the quality of life of these patients varies according to different investigators, who described results that are lower, similar, or better than those in younger patients. Not unexpectedly, mortality is higher among the elderly dialysis patients in whom cardiovascular diseases and infections are the most common causes of death. In elderly patients, an adequate social support system, of which the family unit is the crucial component, is an important element in any form of chronic dialysis. ESRD treatment in the elderly raises many ethical issues and dilemmas. Nephrologists, citizens, politicians, and bureaucrats are concerned about the high cost of long-term therapy. Conflicts over treatment futility and rationing are inevitable. The financial restrictions on dialysis resources have had a powerful impact on patient selection; when the health care resources become limited, the elderly are the first group to be considered expendable. The most common dilemma faced by the nephrologist is the withholding and/or withdrawing of treatment from older patients.
Planimetric studies of peritoneal surface area were performed in 10 humans, 12 rabbits, and 15 rats. It was found that the total peritoneal surface area (TPSA) correlated in humans with body surface area (BSA) (r = 0.98, p < 0.0001) and body weight (r = 0.93, p < 0.001), and correlated in animals with body weight (r = 0.80, p < 0.005 in rabbits; and r = 0.88, p < 0.0001 in rats). The area of parietal peritoneum was 18.1 +/- 1.8% of TPSA in humans, 17.8 +/- 1.0% of TPSA in rabbits, and 22.6 +/- 2.1% of TPSA in rats (p < 0.001 vs humans and rabbits). Additionally, the area of peritoneum covering the individual organs (expressed as % of TPSA) was different in humans, rabbits, and rats: for example, the area of peritoneum covering the diaphragm was 6.4 +/- 1.5% of TPSA in humans, which was larger than in animals (3.0 +/- 0.3% in rats, p < 0.0001 vs humans and rabbits; and only 2.1 +/- 0.4% in rabbits, p < 0.0001 vs humans). Presented results show that interspecies variation in the topography of the peritoneum should be taken into account when the results from experimental studies done on animals are extrapolated to humans.
Hydrogen peroxide can be indirectly detected in mesothelial cells by measuring the rate of inhibition of the intracellular catalase activity by 3-amino-1, 2,3-triazole (AT). AT binds and inhibits catalase only in the presence of hydrogen peroxide, and the effect is proportional to the amount of hydrogen peroxide. The effect of AT on catalase activity is prevented in the presence of ethanol. In mesothelial cells in vitro exposed to dialysis fluids (Dianeal 1.36%, 2.27%, and 3.86%) no significantly increased generation of hydrogen peroxide was detected. However, interleukin-1 (IL-1) (10 ng/mL) enhances, within two hours (+40%, p < 0.05), intracellular production of hydrogen peroxide. The presented method of detection of intracellular hydrogen peroxide may be helpful in studies of the pathomechanisms causing mesothelial damage in conditions of peritoneal dialysis.
Clinical data and outcomes of 18 patients, aged 80 or older, on continuous ambulatory peritoneal dialysis (CAPD) during the last five years were reviewed. There were 12 males and 6 females, with a mean age of 85 (range 82-91 years) and median duration on CAPD of 31.5 months (range 2-58 months). End-stage renal disease was caused by nephrosclerosis in 9, diabetes mellitus and light chain disease in 2 each, and chronic glomerulonephritis, membranous nephropathy, and IgA nephropathy in 1 each, with the cause unknown in yet another 2 patients. Hypertension and angina were the commonest comorbid conditions observed. Peritonitis episodes occurred one per 10.8 patient-months, and necessitated catheter removal in 7 patients and reinsertion in 6 of them. Fourteen episodes of exit-site infections were seen in 8 patients, 2 developed pericatheter leak, and 1 had tunnel infection. Nine patients are continuing CAPD successfully, with a median duration of 29 months (range 11-57 months). One patient was transferred to hemodialysis, and 8 died. The causes of death were peritonitis (3/8), cerebrovascular accident (2/8), pneumonia (1/8), and septicemia (1/8), with the cause not known in 1 patient. Our survival rate of 80% at three years is encouraging, and we advocate CAPD as a successful alternative treatment modality in octogenarians.