Effects of icodextrin on patient survival and technique success in patients undergoing peritoneal dialysis.

BACKGROUND: Many studies have suggested clinical benefits of icodextrin in peritoneal dialysis (PD) patients regarding fluid management, glycaemic control and metabolic improvement. However, reports on whether icodextrin can improve patient and technique survival is sparse. METHODS: A total of 2163 patients from 54 centres in Korea who initiated PD from July 2003 to December 2006 were enrolled. Outcomes data were retrieved retrospectively from the Baxter Korea database. Among these patients, 641 patients who had been prescribed icodextrin for >50% of their PD duration were defined as the 'icodextrin' group and the remaining 1522 patients as the 'non-icodextrin' group. Propensity score matching yielded 640 matched pairs of patients. We compared all-cause mortality and technique failure rates between the two groups. RESULTS: There were no significant differences in age, gender, diabetes, cardiovascular comorbidity, socioeconomic status, biocompatible solution use in short dwells or centre experience between the two groups. Death occurred in 92 (14.4%) patients in the icodextrin group compared with 128 (20.0%) in the non-icodextrin group [hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.53-0.90; P = 0.006]. In addition, icodextrin use was associated with a significantly lower risk of technique failure (HR, 0.60; 95% CI, 0.40-0.92; P = 0.018). The icodextrin group had fewer technique failures due to non-compliance compared with the non-icodextrin group whereas peritonitis- or ultrafiltration failure-related technique failure was not different between the two groups. CONCLUSION: This study further supports previous findings of long-term utilization of icodextrin solution improving patient and technique survival in PD patients. To confirm these results, a large randomized prospective study is warranted.

Peritoneal dialysis practice in Australia and New Zealand: a call to action.

Peritoneal dialysis technique survival in Australia and New Zealand is lower than in other parts of the world. More than two-thirds of technique failures are related to infective complications (predominantly peritonitis) and 'social reasons'. Practice patterns vary widely and more than one-third of peritoneal dialysis units do not meet the International Society of Peritoneal Dialysis minimum accepted peritonitis rate. In many cases, poor peritonitis outcomes reflect significant deviations from international guidelines. In this paper we propose a series of practical recommendations to improve outcomes in peritoneal dialysis patients through appropriate patient selection, prophylaxis and treatment of infectious complications, investigation of social causes of technique failure and a greater focus on patient education and clinical governance.

Mortality and technique failure in peritoneal dialysis patients using advanced peritoneal dialysis solutions.

BACKGROUND: Despite the theoretical benefits of biocompatible physiological-pH bicarbonate/lactate-buffered (B/L) peritoneal dialysis solution, there is only limited evidence supporting a superior clinical outcome associated with its use. STUDY DESIGN: Observational study. SETTINGS & PARTICIPANTS: 2,163 patients starting peritoneal dialysis therapy between July 2003 and December 2006 from 54 centers in Korea were enrolled. PREDICTORS: B/L solution and icodextrin use. OUTCOMES: All-cause mortality and technique failure. MEASUREMENTS: Patient outcomes were compared between patients prescribed B/L and conventional solutions by using propensity score and intention-to-treat analyses. RESULTS: 542 patients initiated peritoneal dialysis therapy with B/L solution, and 1,621, with conventional solution. Fifteen patients prescribed B/L solution switched to conventional solution, and 386 of those initially using conventional solution switched to B/L solution during follow-up. Propensity score matching yielded 542 matched pairs of patients. In the matched cohort, there were no significant differences in age, diabetes, cardiovascular comorbidity, socioeconomic status, icodextrin use, or center experience between the 2 groups. All-cause deaths occurred in 52 (9.6%) patients in the B/L-solution group compared with 102 (18.9%) in the conventional-solution group (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.50 to 0.98; P = 0.04). In addition, icodextrin use was significantly associated with a reduced risk of death (HR, 0.40; 95% CI, 0.28 to 0.58; P < 0.001). Thirty-three (6.1%) and 48 (8.9%) technique failures occurred in the B/L- and conventional-solution groups, respectively (HR, 0.91; 95% CI, 0.58 to 1.43; P = 0.7). The survival benefit of B/L solution persisted in the unmatched cohort (HR, 0.69; 95% CI, 0.52 to 0.93; P = 0.02). LIMITATIONS: Retrospective analysis, lack of laboratory data, and unknown indications for use of B/L solution. CONCLUSION: Use of a biocompatible B/L peritoneal dialysis solution with physiological pH is associated with improved survival compared with conventional solution. Large randomized clinical trials are warranted to confirm this finding.

Frequencies of hepatitis B and C infections among haemodialysis and peritoneal dialysis patients in Asia-Pacific countries: analysis of registry data.

BACKGROUND: The impact of dialysis modality on the rates and types of infectious complications has not been well studied. The aim of the present investigation was to evaluate the rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in peritoneal dialysis (PD) and haemodialysis (HD) patients in the Asia-Pacific region. METHODS: The study included the most recent period-prevalent data recorded in the national or regional dialysis registries of the 10 Asia-Pacific countries/areas (Australia, New Zealand, Japan, China, Taiwan, Korea, Thailand, Hong Kong, Malaysia and India), where such data were available. Longitudinal data were also available for all incident Australian and New Zealand patients commencing dialysis between 1 April 1995 and 31 December 2005. Rates of HCV and HBV infections were compared by chi-square, Poisson regression and Kaplan-Meier survival analyses, as appropriate. RESULTS: Data were obtained on 201,590 patients (HD 173,788; PD 27,802). HCV seroprevalences ranged between 0.7% and 18.1% across different countries and were generally higher in HD versus PD populations (7.9% +/- 5.5% versus 3.0% +/- 2.0%, P = 0.01). Seroconversion rates on dialysis were also significantly higher in HD patients (incidence rate ratio PD versus HD 0.33, 95% CI 0.13-0.75). HCV infection was highly predictive of mortality in Japan (relative risk 1.37, 95% CI 1.15-1.62, P = 0.003) and in Australia and New Zealand (adjusted hazards ratio 1.29, 95% CI 1.05-1.58). HBV infection data were limited, but less clearly influenced by dialysis modality. CONCLUSIONS: Dialysis modality selection significantly influences the risk of HCV infection experienced by end-stage renal failure patients in the Asia-Pacific region. No such association could be identified for HBV infection.

Immune dysfunction in dialysis patients--prevention and treatment strategies.

Immune dysfunction, resulting in infection or inflammation, or both, is closely associated with poor clinical outcome in end-stage renal disease patients. So far, no single measure can effectively address this condition, because many factors, such as uremia per se and dialysis treatment are involved in the pathogenesis. Our review focuses on currently available treatments and prevention options, and identifies future research needs.

Aspects of immune dysfunction in end-stage renal disease.

End-stage renal disease (ESRD) is associated with significantly increased morbidity and mortality resulting from cardiovascular disease (CVD) and infections, accounting for 50% and 20%, respectively, of the total mortality in ESRD patients. It is possible that these two complications are linked to alterations in the immune system in ESRD, as uremia is associated with a state of immune dysfunction characterized by immunodepression that contributes to the high prevalence of infections among these patients, as well as by immunoactivation resulting in inflammation that may contribute to CVD. This review describes disorders of the innate and adaptive immune systems in ESRD, underlining the specific role of ESRD-associated disturbances of Toll-like receptors. Finally, based on the emerging links between the alterations of immune system, CVD, and infections in ESRD patients, it emphasizes the potential role of the immune dysfunction in ESRD as an underlying cause for the high mortality in this patient population and the need for more studies in this area.

Longitudinal relationships between fluid status, inflammation, urine volume and plasma metabolites of icodextrin in patients randomized to glucose or icodextrin for the long exchange.

BACKGROUND: Randomized trials have shown that icodextrin reduces the volume of extra-cellular fluid (ECFv) with variable effects on residual renal function. To explore this fluid shift and its possible mechanisms in more detail, prospectively collected data from one such trial, including measures of inflammation (C-reactive protein, tumour necrosis factor-alpha, albumin and low and high molecular weight hyaluronan) ANP (atrial naturetic peptide), an indirect marker of intra-vascular volume, plasma concentrations of icodextrin metabolites and alpha-amylase activity were analysed. METHODS: 50 patients were randomized to either 2.27% glucose or icodextrin (n = 28) for a long exchange following a month run in. Blood samples were obtained at -1, 0, 3 and 6 months, coincident with measurements of urine volume and fluid status. RESULTS: In both randomized groups, a significant correlation between the fall in ECFv and the decline in urine volume was observed (P = 0.001), although the relative drop in urine volume for patients randomized to icodextrin tended to be less. At baseline, ANP was higher in patients with proportionately more ECFv for a given body water or height. Icodextrin patients had non-significantly higher ANP levels at baseline, whereas by 3 (P = 0.026) and 6 months (P = 0.016) these differed between groups due to divergence. There was a correlation between increasing ANP and reduced ECF at 3 months, r = -0.46, P = 0.007, in patients randomized to icodextrin, but not glucose. There were no relationships between fluid status and any inflammatory markers at any point of the study, with the exception of albumin at baseline, r = -0.39, P = 0.007. Amylase activities at -1 month and baseline were highly correlated, r = 0.89, P < 0.0001. Within patients, concentrations of icodextrin metabolites were highly correlated; the only predictor of between-patient variability on multivariate analysis was body weight. There was no relationship between plasma concentrations of icodextrin metabolites and any of the other clinical parameters, including change in daily ultrafiltration, urine volume, fluid or inflammatory status. CONCLUSIONS: This analysis supports observational data that changes in fluid status are associated with changes in urine volume. Icodextrin was not associated with a greater fall in urine output despite its larger effect on ECFv. Changes in fluid status could not be explained or did not appear to influence systemic inflammation. Nor can they be explained by individual variability in plasma concentrations of icodextrin that are in turn inversely proportional to the volume of distribution.

Icodextrin reduces mortality and the drop-out rate in Japanese peritoneal dialysis patients.

Although numerous reports have shown that the use of icodextrin solution, as compared with conventional dextrose solutions, provides various clinical benefits, data on the impact of icodextrin solution on mortality and drop-out are sparse. In the present retrospective study, we compared clinical outcomes in a large cohort of patients prescribed either icodextrin or dextrose solution for the long dwell. A total of 7808 patients across Japan who were using Baxter peritoneal dialysis (PD) solutions in 2004 were included in this cross-sectional analysis. Outcomes data were retrieved from the Baxter Japan database. The annual drop-out rate in the icodextrin group (8.9%) was significantly (p < 0.0001) lower than that in the dextrose group (14.5%). The annual mortality rate was also lower (6.6% vs. 13.5%, p < 0.0001). Using data from the 2000 report of the Japanese Society for Dialysis Therapy, the relative risk of death in the icodextrin group, regardless of PD duration, was consistently lower than that in hemodialysis patients. These results indicate that, in PD, the use of icodextrin solution (as compared with dextrose solution) significantly reduces both mortality and drop-out rate.

A historical review of encapsulating peritoneal sclerosis.

Publications providing insights into the pathophysiology of, and therapeutic strategies for, EPS are the focus of the present review. Referenced publications are limited to those written in English.

Recommendations on the management of encapsulating peritoneal sclerosis in Japan, 2005: diagnosis, predictive markers, treatment, and preventive measures.

This comprehensive update on the management of encapsulating peritoneal sclerosis incorporates insights gained from recently published findings and the accumulated experience of the authors. Aspects covered include diagnosis, risk factors and predictive markers, treatment, and prevention, including criteria for withdrawal from peritoneal dialysis.

Longitudinal membrane function in functionally anuric patients treated with APD: data from EAPOS on the effects of glucose and icodextrin prescription.

BACKGROUND: Peritoneal dialysis is associated with changes in membrane function that can lead eventually to ultrafiltration (UF) failure. Factors driving these changes are thought to include hypertonic glucose exposure, but previously reported associations are confounded by the presence of residual renal function. METHODS: Longitudinal membrane function (solute transport and UF capacity) were measured annually in a prospective cohort of 177 functionally anuric patients as part of the European Automated Peritoneal Dialysis Outcomes Study (EAPOS). Subgroup analysis was performed according to glucose exposure and icodextrin use at baseline. RESULTS: The whole cohort experienced an increase in solute transport and reduction in UF capacity at 12 and 24 months that could not be explained by informative censoring. These changes were accelerated and more severe in patients using either 2.27% or 3.86% glucose, or those not using icodextrin at baseline. These differences could not be explained by age, comorbidity score, previous time spent on renal replacement, differential dropout from the study, peritonitis rates, or, by definition, residual renal function. Patients using icodextrin at baseline had worse membrane function and were more likely to be diabetic. There was an association between membrane function changes and achieved 24-hour ultrafiltration over the 2-year study period. CONCLUSION: Anuric automated peritoneal dialysis (APD) patients experience significant detrimental changes in membrane function over a relatively short time period. Glucose appears to enhance these changes independent of residual renal function. Icodextrin use in these circumstances is associated with less deterioration in membrane function.

Peritoneal ultrafiltration and serum icodextrin concentration during dialysis with 7.5% icodextrin solution in Japanese patients.

OBJECTIVES: To assess the efficacy and safety of icodextrin in Japanese patients and to investigate the relationship between net ultrafiltration (UF) during the long dwell and plasma oligosaccharides. DESIGN: Open-labeled clinical trial involving patients on continuous ambulatory peritoneal dialysis (CAPD) receiving icodextrin during the 12-hour long dwell for 6 weeks, preceded by and followed by a 2-week baseline period and a follow-up period during which 1.36% glucose was used for the 8-hour long dwell. SETTING: A prospective, randomized multicenter study done in tertiary medical centers. PATIENTS: 18 stable patients on CAPD for 3 months or longer. MAIN OUTCOMES MEASURES: Net UF (in milliliters), UF rate (in milliliters per hour), plasma oligosaccharides, serum osmolarity (in milliosmoles per liter), peritoneal absorption of icodextrin, and peritoneal clearances of icodextrin, creatinine, and urea were assessed. Adverse events, laboratory findings, and vital signs were also monitored. RESULTS: Long-dwell net UF (544.4 +/- 96.7 mL at day 3, p < 0.001; 309.4 +/- 60.7 mL at week 4, p < 0.001; and 391.7 +/- 61.1 mL at week 6, p < 0.001) and UF rate (48.2 +/- 38.8 mL/ hour at day 3, p < 0.001; 26.9 +/- 22.1 mL/hr at week 4, p < 0.002; and 35.3 +/- 22.9 mL/hr at week 6, p = 0.0002) were significantly greater during the icodextrin period than at baseline (-25.9 +/- 46.0 mL and -2.2 +/- 22.1 mL/hr, respectively). Plasma oligosaccharides reached steady state within 2 weeks, remained stable during the treatment period, and returned to baseline level 2 weeks after discontinuation of icodextrin. Serum osmolarity increased during the use of icodextrin by approximately 5 mOsm/L. No statistically significant relationship was found between plasma oligosaccharides and net UF. Peritoneal absorption of icodextrin (36.3% +/- 5.1% at day 3, 42.2% +/- 5.9% at week 4, and 38.0% +/- 6.3% at week 6) and peritoneal clearance of icodextrin (10.1 mL/minute at day 3, 10.1 mL/min at week 4, and 10.3 mL/min at week 6) showed no major change over time. Serum sodium and serum chloride both decreased by 5 mEq/L with icodextrin but remained within the normal range during the treatment period and returned to baseline levels immediately after discontinuation. No serious adverse events were observed during the study. CONCLUSION: The results of this study do not support the hypothesis that an increased blood oligosaccharide level and the concomitant elevation in serum osmolarity have a negative impact on peritoneal UF. Therefore, the increase in plasma oligosaccharides appears to be too small to be of clinical significance.

Icodextrin improves the fluid status of peritoneal dialysis patients: results of a double-blind randomized controlled trial.

Worsening fluid balance results in reduced technique and patient survival in peritoneal dialysis. Under these conditions, the glucose polymer icodextrin is known to enhance ultrafiltration in the long dwell. A multicenter, randomized, double-blind, controlled trial was undertaken to compare icodextrin versus 2.27% glucose to establish whether icodextrin improves fluid status. Fifty patients with urine output <750 ml/d, high solute transport, and either treated hypertension or untreated BP >140/90 mmHg, or a requirement for the equivalent of all 2.27% glucose exchanges, were randomized 1:1 and evaluated at 1, 3, and 6 mo. Members of the icodextrin group lost weight, whereas the control group gained weight. Similar differences in total body water were observed, largely explained by reduced extracellular fluid volume in those receiving icodextrin, who also achieved better ultrafiltration and total sodium losses at 3 mo (P < 0.05) and had better maintenance of urine volume at 6 mo (P = 0.039). In patients fulfilling the study's inclusion criteria, the use of icodextrin, when compared with 2.27% glucose, in the long exchange improves fluid removal and status in peritoneal dialysis. This effect is apparent within 1 mo of commencement and was sustained for 6 mo without harmful effects on residual renal function.

A prospective randomized study of the effect of a subcutaneously "buried" peritoneal dialysis catheter technique versus standard technique on the incidence of peritonitis and exit-site infection.

OBJECTIVE: A new method for implantation of peritoneal dialysis (PD) catheters was described in 1991. The distal part of the catheter is buried subcutaneously and exteriorized at the start of PD. This study was designed to evaluate the effect of such a subcutaneous rest period on the incidence of peritonitis and exit-site infections (ESI). DESIGN: Sixty patients were randomized to either the new method (B group; n = 30) or to not having the distal part buried subcutaneously (NB group; n = 30). Sixty-five patients (NS group) were not randomized as they had to start PD within 1-2 weeks after implantation. The Moncrief-Popovich catheter was used in the B and NB groups and a standard Tenckhoff catheter was used in the NS group. PATIENTS: Patients scheduled for PD treatment, judged not in need of PD for at least 6 weeks after implantation. RESULTS: There was no statistically significant difference in the cumulative probability of not developing peritonitis during the first 6, 12, and 24 months. The incidence of the first episode of peritonitis was 1/40, 1/26, and 1/33 treatment-months in the B, NB, and NS groups, respectively. The incidence of ESI was 1/103 and 1/95 treatment-months in the B and NS groups, respectively. The cumulative probability of not developing ESI was similar in both groups. There were no episodes of ESI in the NB group. The difference in the number of ESI between the NB and NS groups was significant (p < 0.05). CONCLUSIONS: Subcutaneous burying of the distal catheter segment prior to starting PD does not reduce the risk of contracting peritonitis or exit-site infection.

Efficacy and safety of a 7.5% icodextrin peritoneal dialysis solution in patients treated with automated peritoneal dialysis.

In a randomized, prospective, multicenter study, we compared the safety, efficacy, and metabolic effects of a 7.5% icodextrin solution (Extraneal) with a 2.27% glucose solution for long dwell exchanges in patients undergoing automated peritoneal dialysis. Thirty-nine stable patients on automated peritoneal dialysis were randomized to receive either icodextrin (n = 20) or glucose 2.27% solution (n = 19). The study included a 2-week baseline period followed by a 12-week icodextrin treatment phase and a 2-week follow-up period when switching back to glucose. The average net ultrafiltration during the long dwell period was 278 +/- 43 mL/d for the icodextrin group and -138 +/- 81 mL/d for the control group (P < 0.001). The higher ultrafiltration volume with icodextrin was associated with higher creatinine (2.59 +/- 0.09 mL/min versus 2.16 +/- 0.11 mL/min) and urea (2.67 +/- 0.09 mL/min versus 2.28 +/- 0.12 mL/min) peritoneal clearances for the long dwell (both P < 0.001). Ultrafiltration rate per mass of carbohydrate absorbed was +5.2 +/- 1.2 microL/min/g in the icodextrin group and -5.5 +/- 2.8 microL/min/g in the glucose group (P < 0.001). In the icodextrin group, there was a decrease in serum sodium and chloride compared with baseline (P < 0.01). Total dialysate sodium removal increased in the icodextrin group from 226.7 mEq to 269.6 mEq (week 12, P < 0.001). Serum alpha-amylase activity decreased from 103 U/L to 16 U/L (P < 0.001). The total icodextrin plasma levels reached a steady-state concentration of 6,187 +/- 399 mg/L after 1 week of treatment. Urine volume and residual renal function were not specifically affected by icodextrin compared with glucose. None of the laboratory changes resulted in any reported clinically meaningful side effect. Icodextrin produced increased, sustained ultrafiltration during the long dwell period, increasing (convective) peritoneal clearance and sodium removal in automated peritoneal dialysis patients.