Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis

To study the metabolism of icodextrin and α–amylase activity following daily exposure to dialysis solutions containing either glucose or icodextrin as osmotic agent in rats.

Male Wistar rats with implanted peritoneal catheters were infused twice daily for 3 weeks with 20 mL 7.5% icodextrin-based peritoneal dialysis fluid (IPDF; ICO group, n = 12) or 3.86% glucose-based peritoneal dialysis fluid (GLU group, n = 11). A 4-hour dwell study using 30 mL IPDF was performed on day 10 (D1) and day 21 (D2) in both the ICO and the GLU groups. Radiolabeled serum albumin (RISA) was used as a macromolecular volume marker. Dialysate samples were collected at 3, 15, 30, 60, 90, 120, and 240 minutes. Blood samples were drawn before the start and at the end of the dwell.

During all dwell studies, the dialysate concentrations of total icodextrin decreased due to decrease in high molecular weight (MW) fractions, whereas there was a marked increase in icodextrin low MW metabolites. α–Amylase activity increased in dialysate and decreased in plasma. About 60% of the total icodextrin was absorbed from the peritoneal cavity during the 4-hour dwells. Low MW icodextrin metabolites were present in the dialysate already at 3 minutes, and maltose (G2), maltotriose (G3), maltotetraose (G4), and maltopentaose (G5) increased progressively, reaching maximum concentrations at 60 minutes. Maltohexaose (G6) and maltoheptaose (G7) were also detected already at 3 minutes but did not change significantly during the dwells. During the two 4-hour dwell studies (D1 and D2), the concentrations of total icodextrin and icodextrin metabolites and α–amylase activity in dialysate did not differ between the ICO and GLU groups, during either D1 or D2. No icodextrin metabolites were detected in plasma at the end of the dwells. α–Amylase activity in the dialysate increased six- to eightfold whereas plasma α–amylase activity decreased by 21% – 26% during the two 4-hour dwells in both the ICO and the GLU groups; there were no significant differences between the ICO and the GLU groups during either D1 or D2. α–Amylase activity in the dialysate correlated strongly with the disappearance rate of icodextrin from the peritoneal cavity during the 4-hour dwells, and with the concentrations of G2, G3, G6, and G7 in dialysate.

The decline in the dialysate concentrations of high MW fractions and the increase in low MW metabolites of icodextrin suggest intraperitoneal α–amylase mediated the metabolism of icodextrin and the transport of predominantly the smaller icodextrin metabolites from dialysate. However, no icodextrin could be detected in plasma, suggesting that it was metabolized and excreted by the kidney in these nonuremic rats. In contrast to uremic peritoneal dialysis patients, chronic exposure to IPDF did not seem to further affect α–amylase activity or icodextrin metabolism. The much higher α–amylase activity in plasma and dialysate in rats than in humans explains the much more rapid metabolism of icodextrin in rats compared with peritoneal dialysis patients.

Bacterial peritonitis episodes may disturb the functional and histological integrity of the peritoneum in peritoneal dialysis patients. The renin–angiotensin–aldosterone system may have fibrotic effects on the peritoneum.

To study the effects of an angiotensin II receptor antagonist (irbesartan) and an aldosterone antagonist (spironolactone) in the prevention of peritoneal fibrosis in a rat model of bacterial peritonitis.

40 Wistar rats were randomized into 5 groups: bacteria (B), bacteria–irbesartan (BI), bacteria–spironolactone (BS), bacteria–irbesartan–spironolactone (BIS), and control (C) groups. The C group received only dextran beads (Cytodex; Sigma Chemicals, St Louis, Missouri, USA); the others were given bacteria and dextran beads intraperitoneally. Irbesartan and/or spironolactone were given to 3 groups: BI, BS, and BIS. On the eighth day, the rats were sacrificed, peritoneal adhesion was quantified, and peritoneal tissue sections were evaluated histologically.

The peritoneal total adhesion score was significantly higher in the B group than in the BI, BIS, and C groups (p < 0.01). Mean peritoneal thickness, mean inflammation score, and mean fibrosis score were significantly higher in the B group in comparison to the C group (p < 0.05). Mean peritoneal thickness of all treatment groups was significantly lower than the B group (p < 0.05). Serum transforming growth factor beta-1 level was significantly higher in the B group than in the BI, BS, and C groups (p < 0.05).

Irbesartan and spironolactone seem to decrease the extent of peritoneal injury caused by bacterial peritonitis.

Continuous ambulatory peritoneal dialysis (CAPD) is an established treatment for end-stage renal disease (ESRD). We investigated the outcome of CAPD over a period of 25 years at our institution.

CAPD has been performed in 2301 patients in 25 years. After excluding patients with less than 3 months of follow-up and missing data, we evaluated 1656 patients who started peritoneal dialysis between November 1981 and December 2005. Data for sex, age, primary disease, co-morbidities, follow-up duration, cause of death, and cause of technique failure were collected. We also examined data for urea kinetic modeling (UKM), beginning in 1990, and peritonitis episodes, including causative organisms, starting in 1992.

Compared to incident patients from 1981 – 1992, mean age and incidence of ESRD caused by diabetic nephropathy increased in patients from 1993 to 2005. Technique survival after 5 and 10 years was 71.9% and 48.1% respectively. Technique survival was significantly higher in patients who started CAPD after 1992 than in those who started before 1992. Peritonitis was the main reason for technique failure. Overall peritonitis rate was 0.38 episodes per patient-year, with a significant downward trend to 0.29 per patient-year over 10 years, corresponding to a decrease in gram-positive peritonitis. Patient survival after 5 and 10 years was 69.8% and 51.8% respectively. Patient survival improved significantly during 1992 – 2005 compared to 1981 – 1992 after adjustment for age, gender, diabetes, and cardiovascular comorbidities [hazard ratio (HR) 0.68, p < 0.01]. Subgroup analysis based on UKM revealed that dialysis adequacy did not affect patient survival. However, diabetes (HR 2.78, p < 0.001), older age (per 1 year: HR 1.06; p < 0.001), serum albumin level (per 1 g/dL: increase, HR 0.52; p < 0.05), and cardiovascular comorbidities (HR 2.32, p < 0.01) were identified as significant risk factors.

Technique survival has improved due partly to a decrease in peritonitis, which was attributed to a decrease in gram-positive peritonitis. Patient survival has also improved considering increases in aged patients and ESRD caused by diabetes. The mortality rate of CAPD is still high in older, diabetic, malnourished, and cardiovascular diseased patients. A more careful management of higher risk groups will be needed to improve the outcome of CAPD patients in the future.

The peritoneal equilibration test (PET) is a 4-hour procedure that is recommended to be performed in children receiving peritoneal dialysis to assist in prescription management. While a shortened version of the PET has been used in adults and reliably characterizes peritoneal membrane transport capacity, no similar experience with children has been reported.

Retrospective evaluation of 2-hour and 4-hour PET data obtained from 20 children receiving chronic peritoneal dialysis in a single center. Characterization of membrane transport capacity was based on evaluation of serum and dialysate samples used to determine the dialysate-to-plasma ratio (D/P) of creatinine and the ratio of dialysate glucose to baseline dialysate glucose (D/D₀). Patient values were compared to pediatric reference data.

In all 20 patients, characterization of peritoneal membrane transport capacity using 2-hour D/P and D/D₀ results was identical to that determined using 4-hour data for the same solute. While the creatinine- and glucose-based characterization was discrepant in 14 of 20 patients, in only 1 case was the discrepancy of more than a single transport category.

These results support the accuracy of a short PET in children, a procedure that should prove beneficial in terms of patient and staff time.

Long-term peritoneal dialysis (PD) may lead to peritoneal fibrosis and ultrafiltration failure. The latter occurs due to high solute transport rates and diabetiform peritoneal sclerosis. Angiotensin-II (AII) is known to be a growth factor in the development of fibrosis and a number of animal studies have shown it likely that inhibiting the effects of AII by angiotensin-converting enzyme (ACE) or angiotensin receptor blocker (ARB) will attenuate these complications.

To investigate the effects of ACE/AII inhibitors in long-term PD patients.

We analyzed data from 66 patients treated with PD therapy at our center for at least 2 years, during which time at least 2 standard peritoneal permeability analyses (SPAs) were performed. 36 patients were treated with ACE/AII inhibitors (ACE/ARB group); the other 30 received none of the above drugs during the entire follow-up (control group). The two groups were compared with respect to changes in peritoneal transport over the follow-up time.

A significant difference in time course of peritoneal transport was found between the 2 groups: in the ACE/ARB group, small solute transport had decreased, while it had increased in the control group. This finding was confirmed by analysis using mixed model for repeated measures. The value of mass transfer area coefficient of creatinine was influenced by the duration of PD therapy (p = 0.017) and this interaction was different with respect to use of ACE/AII inhibitors (p = 0.037). The trend was not found in protein clearances or fluid kinetics.

Our findings suggest that ACE/AII inhibition is likely to prevent the increase in mass transfer area coefficients that occurs in long-term PD, which is in line with results of experimental animal studies.