Amadori albumin and advanced glycation end-product formation in peritoneal dialysis using icodextrin.

OBJECTIVE: To study the influence of peritoneal dialysis (PD) solutions on the formation of early glycated products and advanced glycation end-products (AGEs). DESIGN AND PATIENTS: The formation of both Amadori albumin and AGEs in glucose- and icodextrin-based PD fluids was analyzed in vitro and in peritoneal effluents of continuous cyclic peritoneal dialysis (CCPD) patients. RESULTS: Albumin incubated with glucose-based PD fluids showed a time- and glucose concentration-dependent formation of Amadori albumin and AGEs. Aminoguanidine completely inhibited AGE but not Amadori albumin formation. Albumin incubated in icodextrin resulted in the lowest levels of Amadori albumin and AGE. Amadori albumin levels in effluents of 24 CCPD patients (12 glucose and 12 icodextrin for their daytime dwells) were similar. Dialysate samples collected during a mass transfer area coefficient test in 16 CCPD patients (8 glucose, 8 icodextrin) showed an increase in Amadori albumin formation from baseline (p < 0.0001), without a difference between the groups. In the total group, there was a positive relationship between duration on PD and dialysate Amadori albumin concentration at 240 minutes (p = 0.03). The Amadori albumin dialysate-to-plasma (D/P) ratio at 240 minutes was 0.82+/-0.11, and its clearance amounted to 7.71+/-1.14 mL/min, while the albumin D/P ratio was 0.010+/-0.003 and its clearance was 0.089+/-0.017 mL/min. In a peritoneal biopsy of a CCPD patient, Amadori albumin was observed in the mesothelial layer and the endothelium of the peritoneum. CONCLUSIONS: Using icodextrin-based instead of glucose-based PD fluids can largely reduce the formation of Amadori albumin and AGEs. However, CCPD patients using icodextrin during daytime dwells do not have lower effluent levels of Amadori albumin and AGEs, probably due to the exposure to glucose during their nighttime exchanges. Kinetic studies suggest washout of locally produced Amadori albumin.

Assessment of the effectiveness, safety, and biocompatibility of icodextrin in automated peritoneal dialysis. The Dextrin in APD in Amsterdam (DIANA) Group.

OBJECTIVE: Our study assessed the efficacy, safety, and biocompatibility of icodextrin (I) solution compared to glucose (G) solution as the daytime dwell in continuous cycling peritoneal dialysis (CCPD). DESIGN: In a randomized, open, prospective, parallel group study of two year's duration, either I or G was used for the long daytime dwell in CCPD patients. METHOD: The study was carried out in a university hospital and teaching hospital. Established CCPD patients and patients new to the modality were both included. Clinic visits were made at three-month intervals. In all patients, clinical data were gathered; ultrafiltration (UF) was recorded; and serum, urine, and dialysate samples and effluents were collected. Peritoneal defense characteristics and mesothelial markers were determined. Every six months, peritoneal kinetics studies were performed, and serum samples for icodextrin metabolites were taken. RESULTS: Thirty-eight patients (19 G, 19 I) started the study. The median follow-up was 16 months and 17 months respectively (range: 0.5 - 26 months and 3 - 26 months, respectively). Daytime UF volumes increased significantly (p < 0.001), and 24-hour UF tended to increase from baseline in the I group. Dialysate creatinine clearance increased non significantly in both groups over time. In I patients, serum disaccharides (maltose) concentration increased from 0.05+/-0.01 mg/mL [mean+/- standard error of mean (SEM)] at baseline, to an average concentration in the follow-up visits of 1.15+/- 0.04 mg/mL (p <0.001). At the same time, serum sodium levels decreased from 138.1 +/- 0.7 mmol/L to an average concentration in the follow-up visits of 135.9 +/- 0.8 mmol/L (p < 0.050). At 12 months, the serum sodium concentration increased to a non significant difference from baseline. Serum osmolality increased, but did not differ significantly from G users at any visit. During peritonitis (P), daytime dwell UF decreased significantly compared to non peritonitis (NP) episodes in G patients (p < 0.0 01), but remained stable in I patients. Total 24-hour UF also decreased in G patients (p < 0.001), but not in I patients. In these I patients, serum disaccharides increased from 0.05 +/- 0.01 mg/mL to 1.26 +/- 0.2 mg/mL during follow-up. During peritonitis, serum disaccharides concentration did not increase further (1.47 +/- 0.2 mg/mL, p= 0.56). Thirty P episodes occurred during follow-up: 16 in G patients and 14 in I patients (1 per 17.6 months and 1 per 21.9 months, respectively.) After one year, absolute number and percentage of effluent peritoneal macrophages (PM phi s) were significantly higher in I patients than in G patients. The difference in percentage persisted after two years. The phagocytic capacity of PM phi s decreased over time, resulting in a borderline significant difference for coagulase-negative staphylococci phagocytosis (p=0.005) and a significant difference for E. coli phagocytosis (p <0.05) in favor of I patients. PM phi oxidative metabolism, PM phi cytokine production, and effluent opsonic capacity remained stable over time with no difference between the groups. Mass transfer area coefficients (MTACs) and clearances were stable and appeared unaffected by G or I treatment. Effluent cancer antigen 125 (CA125) was stable in G users and tended to decrease in I users. Effluent interleukin-8 (IL-8), carboxy-terminal propeptide of type I procollagen (PICP ), and amino-terminal propeptide of type III procollagen (PIIINP) did not change over time and did not differ between the groups. CONCLUSION: The use of I for the long daytime dwell in CCPD led to an increase in total UF of at least 261 mL per day, which was maintained over at least 24 months. During I treatment, serum I metabolites increased significantly and serum sodium concentrations decreased initially. As a result, serum osmolality increased slightly. Clinical adverse effects did not accompany these findings. The UF gain in the I patients was even higher during P, without a

Peritoneal kinetics and mesothelial markers in CCPD using icodextrin for daytime dwell for two years.

OBJECTIVE: To evaluate the safety, efficacy, and biocompatibility of icodextrin (Ico), continuous cycling peritoneal dialysis (CCPD) patients were treated for 2 years with either Ico- or glucose (Glu)-containing dialysis fluid for their daytime dwell (14 - 15 hours). Prior to entry into the study, all patients used standard Glu solutions (Dianeal, Baxter BV, Utrecht,The Netherlands). DESIGN: Open, randomized, prospective two-center study. SETTING: University hospital and teaching hospital. PATIENTS: Both established patients and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years or with peritonitis in the previous month, and women of childbearing potential unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients entered the study (19 Glu, 19 Ico). MAIN OUTCOME MEASURES: Daytime dwell peritoneal effluents were collected every 3 months in combination with other study variables (clinical data, laboratory measurements, dialysis-related data, and urine collection). Peritoneal transport studies were carried out every 6 months. RESULTS: In Glu- and Ico-treated patients, peritoneal transport of low molecular weight solutes and protein clearances neither changed during follow-up nor differed between the two groups. Peritoneal membrane markers (CA125, interleukin-8, carboxyterminal propeptide of type I procollagen, and aminoterminal propeptide of type III procollagen) measured in effluents did not differ between the groups and did not change over time. All these markers showed a dialysate/plasma ratio of more than 1, suggesting local production. Residual renal function remained stable during follow-up and adverse clinical effects were not observed. CONCLUSIONS: Peritoneal membrane transport kinetics and markers remained stable in both groups over a 2-year follow-up period. Membrane markers were higher in effluents than in serum, suggesting local production. No clinical side effects were demonstrated. Icodextrin was a well-tolerated effective treatment.

Induction of 1,2-dicarbonyl compounds, intermediates in the formation of advanced glycation end-products, during heat-sterilization of glucose-based peritoneal dialysis fluids.

OBJECTIVE: To study the presence of 1,2-dicarbonyl compounds in peritoneal dialysis (PD) fluids, their concentration in effluents with increasing dwell time, and their role in the formation of advanced glycation end-products (AGEs). MEASUREMENTS: Dicarbonyl compounds in heat- and filter-sterilized PD fluids were quantified by reverse-phase high performance liquid chromatography (HPLC) after derivatization to dimethoxyquinoxaline derivatives. Kinetics of the in vitro formation of AGEs upon incubation of 1,2-dicarbonyl compounds or PD fluids with albumin, with or without aminoguanidine, were measured by AGE fluorescence (excitation/emission wavelengths of 350 nm/430 nm). PATIENTS: AGEs and dicarbonyl compounds were measured in effluents collected from standardized 4-hour dwells from 8 continuous cycling peritoneal dialysis patients. RESULTS: In PD fluids, 3-deoxyglucosone (3-DG) has been identified as the major dicarbonyl compound formed during the process of heat sterilization. The process also formed glyoxal (GO) and methylglyoxal (MGO), with the amount of 3-DG being approximately 25-60 times higher than GO and MGO. When incubated with albumin, the identified 1,2-dicarbonyl compounds rapidly formed AGEs. The formation of AGEs was more pronounced in conventional heat-sterilized PD fluids compared with filter-sterilized PD fluids, and was completely inhibited by aminoguanidine. In effluents, the concentration of MGO, GO, and 3-DG decreased with increasing dwell time, with a concomitant increase in AGE fluorescence. CONCLUSIONS: The dicarbonyl compounds 3-DG, MGO, and GO are potent promoters of AGE formation. The presence of these and possibly other dicarbonyl compounds formed during heat sterilization of glucose-based PD fluids is, to a large extent, responsible for the in vitroAGE formation by these fluids, as evidenced by the speed of AGE formation in PD fluids and the complete inhibition by aminoguanidine. Because 3-DG, MGO, and GO are rapidly cleared from PD fluids during dialysis, these compounds may contribute to the in vivo AGE formation in PD patients.

Peritoneal defense using icodextrin or glucose for daytime dwell in CCPD patients.

OBJECTIVE: To investigate peritoneal defense during icodextrin use in continuous cyclic peritoneal dialysis (CCPD). DESIGN: In an open, prospective, 2-year follow-up study, CCPD patients were randomized to either glucose (Glu) or icodextrin (Ico) for their long daytime dwell. SETTING: University hospital and teaching hospital. PATIENTS: Both established and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years, those who had peritonitis in the previous month, and women of childbearing potential, unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients (19 Glu, 19 Ico) started the study. The median follow-up was 16 and 17 months for Glu and Ico respectively (range 0.5-25 months and 5-25 months, respectively). OUTCOME MEASURES: Peritoneal defense characteristics and peritoneal dialysis-related infections were recorded every 3 months. RESULTS: Total peritoneal white cell count tended to decrease over time in both groups. After 1 year, absolute numbers and percentages of effluent peritoneal macrophages (PMphis) were significantly higher in Ico than in Glu patients; this difference in the percentage persisted after 2 years. Percentage of mesothelial cells increased overtime in Ico patients. The phagocytic capacity of PMphis decreased over time, resulting in a borderline significant difference for coagulase-negative staphylococci (p = 0.05) and a significant difference for Escherichia coli (p < 0.05) phagocytosis in favor of Ico patients. PMphi oxidative metabolism remained stable over time without a difference between the groups. PMphi cytokine production and effluent opsonic capacity also remained stable over time. Finally, 16 peritonitis episodes in Glu and 14 in Ico patients occurred. Glucose patients had 37 and Ico patients 32 exit-site infections during the study. CONCLUSION: CCPD patients using Ico did equally as well as Glu-treated patients with respect to clinical infections and most peritoneal defense characteristics. However, in a few peritoneal defense tests, Ico-treated patients did better.

Icodextrin use in CCPD patients during peritonitis: ultrafiltration and serum disaccharide concentrations.

BACKGROUND AND METHODS: In a randomized study on the biocompatibility of icodextrin (I) versus glucose (G) in CCPD we used icodextrin or glucose for the long daytime dwell. During the night-time dwells glucose was used in all patients. In case of peritonitis icodextrin was continued. In all patients ultrafiltration (UF) was recorded and serum icodextrin metabolites were determined every 3 months and during peritonitis in I-users when available. RESULTS: Thirty-eight patients ( 19 G, 19 I) entered the study and suffered 30 peritonitis episodes (16 G, 14 I). During peritonitis (P), daytime dwell UF decreased significantly in G (P=0.001), but remained stable in I patients compared to non-peritonitis (NP) episodes. Total 24-h UF decreased in G (P=0.001) and in I patients (P=0.04), as the result of a decreased daytime UF and night-time UF, respectively. There was no difference in the used glucose concentrations during the P versus NP episodes. In five I-patients serum disaccharides increased from 0.05+/-0.01 to 1.26+/-0.23mg/ml during follow up. During peritonitis serum disaccharide concentrations did not increase further (1.47+/-0.24 mg/ml, P= 0.56). In I patients total carbohydrate minus glucose rose to 5.72 +/- 1.2 mg/ml during follow up, and to 6.63 +/- 1.04 mg/ml during peritonitis (P=0.7). These concentrations are comparable to CAPD patients despite the longer dwelltime in CCPD (8-10 versus 14-16 h, respectively). Adverse reactions attributable to icodextrin were not encountered. CONCLUSIONS: In contrast to glucose, icodextrin preserved the daytime dwell ultrafiltration during peritonitis. Serum icodextrin metabolites increased during icodextrin use, but remained stable during peritonitis. Adverse effects were not observed.

Simultaneous peritoneal dialysis catheter insertion and removal in catheter-related infections without interruption of peritoneal dialysis.

Catheter-related infections result in high patient morbidity, the need for temporary haemodialysis, and high costs. These infections are the main cause of limited technique survival in peritoneal dialysis. We introduced a protocol for the simultaneous peritoneoscopic insertion and removal of peritoneal catheters in patients with catheter-related infections. Peritoneal dialysis was continued the day after surgery using low-volume dwells and a dry abdomen during the daytime. The dialysate leukocyte count had to be below 100/mm3 before exchanging catheters, which was performed under antibiotic therapy based on culture sensitivity. The old catheter was removed after the new catheter had been inserted in the opposite abdominal region. CAPD patients were switched to APD for 1 week, which made prolonged hospitalization necessary. Simultaneous catheter insertion and removal was performed 25 times in 22 patients on CCPD and 15 times in 14 patients on CAPD. In CCPD patients, peritoneal dialysis was restarted after 1.0+/-0.1 days in 24 cases. One patient had sufficient residual renal function and discontinued CCPD until day 10. In 10 CAPD patients (11 procedures) APD was started 1.3+/-0.2 days after the procedure with CAPD beginning 7.1+/-0.6 days thereafter. Three CAPD patients preferred haemodialysis and restarted CAPD 10.0+/-2.1 days after surgery. One patient continued CAPD the day after surgery. In addition to minor complications (e.g. position-dependent outflow problems), dialysate leakage occurred in two patients. Two patients developed peritonitis within the first 30 days after surgery, one of which was procedure related. One patient had severe lower gastrointestinal bleeding 2 weeks after the procedure, which was not related to the catheter replacement. Ultimately, in 38 of 40 procedures the patients could successfully continue peritoneal dialysis. We conclude that simultaneous insertion and removal of a peritoneal dialysis catheter without interruption of peritoneal dialysis is a safe procedure in patients with catheter-related infections.

Icodextrin instead of glucose during the daytime dwell in CCPD increases ultrafiltration and 24-h dialysate creatinine clearance.

BACKGROUND AND METHODS: Icodextrin 7.5% is an iso-osmolar, glucose polymer-containing peritoneal dialysis solution with an ultrafiltration potential similar to glucose 3.86%. We compared in an open, randomized, prospective study the ultrafiltration potential of icodextrin with that of glucose during the daytime dwell of 23 patients treated with automated peritoneal dialysis (CCPD). RESULTS: Daytime ultrafiltration volume and 24-h ultrafiltration volume increased significantly in icodextrin-treated patients (n = 11) at 3 and 6 months, allowing patients a less rigid fluid restriction or an adapted treatment schedule. This improved the patients' subjective well-being. Although ultrafiltration at 9 and 12 months also increased it did not reach statistical significance. Similar to the gain in ultrafiltration volume, 24-h dialysate creatinine clearance per 1.73 m2 (DCl/1.73 m2) and DCl/1.73 m2 per litre used dialysate (DCl/1.73 m2/l) increased in icodextrin-treated patients. DCl/1.73 m2/l per litre ultrafiltrate (DCl/1.73 m2/l/UF) did not increase. No side-effects of icodextrin were encountered, although serum disaccharide levels increased. CONCLUSION: Icodextrin enhances ultrafiltration during the daytime dwell in CCPD patients. As a result of an increased 24-h ultrafiltration volume, DCl/1.73 m2 and DCl/1.73 m2/l improve. DCl/1.73 m2/l/UF does not rise, which suggests that the increase in DCl/1.73 m2 and DCl/1.73 m2/l is caused by convective transport.

Serum disaccharides and osmolality in CCPD patients using icodextrin or glucose as daytime dwell.

OBJECTIVE: To evaluate the safety, efficacy, and biocompatibility of icodextrin- and glucose-containing dialysis fluid during continuous cycling peritoneal dialysis (CCPD), patients were treated for 2 years with either icodextrin- or glucose-containing dialysis fluid for their daytime dwell (14-15 hours). Prior to entry into the study, all patients used a standard glucose solution (Dianeal 1.36%, 2.27%, or 3.86%, Baxter, Utrecht, The Netherlands). DESIGN: Open, randomized, prospective, two-center study. SETTING: University hospital and teaching hospital. PATIENTS: Both established and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18, those with peritonitis in the previous month, and women of childbearing potential, unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients entered the study, and 25 (13 glucose, 12 icodextrin) had a follow-up period of 12 months or longer in December 1996. MAIN OUTCOME MEASURES: Serum icodextrin metabolites: one to five glucose units (G1-G5), a high molecular weight fraction (G > 10), and total carbohydrate level, as well as a biochemical profile were determined every 3 months in combination with all other study variables. RESULTS: In icodextrin-treated patients, serum disaccharide (maltose) concentrations increased from 0.05 +/- 0.01 (mean +/- SEM) at baseline, to an average concentration in the follow-up visits of 1.14 +/- 0.13 mg/mL (p < 0.001). All icodextrin metabolites increased significantly from baseline, as illustrated by the serum total carbohydrate minus glucose levels: from 0.42 +/- 0.05 mg/mL to an average concentration in the follow-up visits of 5.04 +/- 0.49 mg/mL (p < 0.001). At the same time, serum sodium levels decreased from 138.1 +/- 0.7 mmol/L to an average concentration in the follow-up visits of 135.4 +/- 0.8 mmol/L (p < 0.05). However, after 12 months the serum sodium concentration increased nonsignificantly (NS) from baseline to 136.6 +/- 0.9 mmol/L, after an initial decrease. Serum osmolality increased significantly from baseline in icodextrin users at 9 and 12 months, but did not differ significantly from glucose users in any visit. In icodextrin-treated patients, the calculated serum osmolal gap increased significantly from 4.1 +/- 1.4 mOsm/kg to an average of 11.8 +/- 1.7 mOsm/kg (p < 0.01). The sum of the serum icodextrin metabolites in millimoles/liter equaled the increase in osmolal gap. Body weight increased in icodextrin users (71.9 +/- 2.8 kg to 77.8 +/- 3.0 kg; NS). Clinical adverse effects did not accompany these findings. Residual renal function remained stable during follow-up. CONCLUSIONS: The serum icodextrin metabolite levels in the present study increased markedly and were the same as those found previously in continuous ambulatory peritoneal dialysis patients treated with icodextrin, despite the longer dwell time for CCPD patients (14-16 hr versus 8-12 hr). The initial decrease in serum sodium concentration was followed by an increase to a concentration not different from baseline at 12 months. The pathophysiology of this finding is speculated. Calculated osmolal gap in icodextrin patients increased significantly (p < 0.01) at every follow-up visit, and could be explained by the serum icodextrin metabolite increase. We encountered no clinical side effects of the observed levels of icodextrin metabolites.

The efficacy of intraperitoneally administered gentamicin and rifampin as initial treatment of peritoneal dialysis-related peritonitis.

For the initial treatment of peritonitis complicating peritoneal dialysis (PD), we use intraperitoneally administered gentamicin (broad spectrum and low costs) and rifampin (intracellular bactericidal activity). In order to assess the efficacy of this treatment, the outcome of 248 suspected episodes of peritonitis (abdominal pain, cloudy effluent, and a leukocyte count over 100/mm3) was evaluated. Of 227 cases with a positive culture of the PD effluent, one bacterial species was cultured in 188 cases (75.8%), more than one in 32 cases (12.9%), and in 7 cases (2.8%) yeasts. In 87.2% of the culture-positive cases, a good clinical response to the initialized antibiotic therapy was found. In 20 cases (8.1%) antibiotic treatment was discontinued within one week because no micro-organisms were cultured. In one case no effluent was cultured. Although in vitro resistance or indifference to both antibiotics was found in 45 cases (19.8%), in only 29 culture-positive cases (12.8%) the clinical condition did not improve on initial therapy. Of the peritonitis episodes in which micro-organisms resistant to both antibiotics were cultured, 23 were Staphylococcus epidermidis, 5 were E. coli, 7 were yeasts, and there were miscellaneous (mostly enteral) bacteria in 10 cases. In the studied period no significant changes were found in the susceptibility of the cultured microorganisms to gentamicin and rifampin. Susceptibility profile per episode, however, showed an increasing resistance against both antibiotics. It is concluded that the combination of gentamicin and rifampin as initial treatment of peritonitis is effective in most (87%) cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Tubular colonic duplication combined with unilateral renal hypoplasia.

Colonic duplication is a rare congenital abnormality that can be difficult to diagnose, because multisystemic malformations may be present. We report on a hypertensive patient with rather nonspecific symptoms in whom previous diagnoses had failed to detect colonic duplication. In addition to a tubular colonic duplication type I, a hypoplastic kidney was found. This combination has not been reported before.