icodextrin and Body-Weight

There are still controversies whether peritoneal dialysis (PD) with icodextrin preserves residual renal and peritoneal membrane functions in patients with diabetes. However, there are no randomized controlled and long-term clinical trials in newly started PD patients with diabetic nephropathy.. Forty-one patients with diabetic nephropathy with ESRD were enrolled and randomly assigned to the glucose group (GLU) treated with 8 L of 1.5% or 2.5% glucose or an icodextrin group (ICO) treated with 1.5 or 2.0 L of 7.5% icodextrin-containing solutions. Technique failure, body fluid management, glucose and lipid metabolism, and residual renal and peritoneal functions and were evaluated over 2 years.. The technique survival rate was 71.4% in ICO and 45.0% in GLU, with most of the technique failure due to volume overload. ICO showed significantly better cumulative technique survival. Net ultrafiltration volume was significantly higher in ICO throughout the study period. There were no beneficial effects of icodextrin on hemoglobin A1c, glycoalbumin, and lipid profile at 24 months. Urine volume and residual renal function declined faster in ICO, but there were no significant differences between the two groups. For peritoneal function, no differences were observed in dialysis-to-plasma creatinine ratios during the observation.. In PD therapy for diabetic nephropathy, the use of icodextrin-containing solutions has a beneficial effect on technique survival, but there are no apparent benefits or disadvantages in residual renal and peritoneal functions compared with conventional PD with glucose solution.

Topics: Aged; Biomarkers; Blood Glucose; Body Weight; Creatinine; Diabetic Nephropathies; Dialysis Solutions; Female; Glucans; Glucose; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Icodextrin; Japan; Kaplan-Meier Estimate; Kidney; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Peritoneal Dialysis; Prospective Studies; Serum Albumin; Time Factors; Treatment Outcome; Water-Electrolyte Balance

The use of dextrose-containing solutions in peritoneal dialysis (PD) is thought to be associated with glucose-related toxicity both to the peritoneal membrane and systemically. There has, therefore, been considerable interest in minimizing the use of dextrose exposure during PD. The present study was designed to explore the use of icodextrin in patients with high/high-average transporter characteristics for two exchanges per day to minimize glucose exposure.. We performed a 6-month prospective cohort study using two icodextrin exchanges per day in a group of high/high-average transporters maintained on automated PD. Icodextrin levels, serum sodium levels, and glucose exposure were measured at baseline, 3 and 6 months.. Nine patients completed the study protocol. While the total volume of PD solution remained the same, there was a reduction in mean glucose exposure from a baseline mean value of 410 +/- 75 to 275 +/- 57 g/day at 3 months and 300 +/- 75 g/day at 6 months. Serum icodextrin levels rose from a baseline mean of 345 +/- 145 to 615 +/- 120 mg/dl at 3 months and 620 +/- 108 mg/dl at 6 months. Serum sodium levels remained stable.. The use of two (double) icodextrin exchanges in high/high-average transporters on PD can contribute to reduction in glucose exposure for patients maintained on automated PD and appears to be safe.

Topics: Adult; Aged; Biological Transport; Body Weight; Diabetic Nephropathies; Drug Administration Schedule; Female; Glucans; Glucose; Hemodialysis Solutions; Humans; Icodextrin; Kidney Failure, Chronic; Male; Middle Aged; Osmolar Concentration; Peritoneal Dialysis, Continuous Ambulatory; Prospective Studies; Sodium

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.. 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.. 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.. 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.

Topics: Amylases; Atrial Natriuretic Factor; Body Weight; C-Reactive Protein; Extracellular Fluid; Glucans; Glucose; Hemodialysis Solutions; Humans; Hyaluronic Acid; Icodextrin; Kidney Failure, Chronic; Multivariate Analysis; Osmolar Concentration; Peritoneal Dialysis; Serum Albumin; Tumor Necrosis Factor-alpha; Ultrafiltration; Urine

Icodextrin is a starch-derived glucose polymer that causes sustained ultrafiltration in long dwells in peritoneal dialysis. The aim of this study was to assess factors that were predictive of an increment in ultrafiltration following the introduction of icodextrin in patients with refractory fluid overload.. Thirty-nine patients (20 male/19 female, mean age 57.7 +/- 2.4 years) on peritoneal dialysis were enrolled in a prospective pretest/post-test, open-label study. All patients had symptomatic fluid overload refractory to fluid restriction (<800 mL/day), frusemide doses of 250 mg or more daily, optimization of dwell time and use of hypertonic dextrose. An icodextrin exchange was substituted for a 4.25% dextrose exchange for the long-dwell period.. After 1 month, median (interquartile range) 24 h ultrafiltration volume increased by 500 mL (interquartile range: 50-1000). An increase in ultrafiltration volume correlated positively with the dialyate : plasma creatinine ratio at 4 h (r = 0.498, P = 0.001) and negatively with the ratio of dialysate glucose concentrations at 4 and 0 h (r = -0.464, P = 0.003). On multivariate regression analysis, high transporter status was predictive of a greater ultrafiltration response to icodextrin relative to dextrose peritoneal dialysis exchanges. Age, sex, race, peritoneal dialysis duration, peritoneal dialysis modality, diabetes mellitus, baseline albumin, and baseline ultrafiltration volume were not significantly correlated with the change in ultrafiltration volume.. Icodextrin significantly augments ultrafiltration volumes in patients with refractory fluid overload. A high peritoneal membrane transporter status is the best predictor of a favourable ultrafiltration response to icodextrin.

Topics: Adult; Aged; Blood Pressure; Body Weight; Dialysis Solutions; Female; Glucans; Glucose; Humans; Icodextrin; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Peritoneum; Predictive Value of Tests; Prospective Studies; Serum Albumin; Treatment Failure; Ultrafiltration

Standard glucose-based peritoneal dialysis (PD) solutions have unfavorable effects on the peritoneum and contribute to metabolic abnormalities. A PD regimen in which solutions with an alternative osmotic agent (icodextrin, amino acids) and solutions with a bicarbonate/lactate buffer are combined may reduce those effects. In a prospective crossover study, we randomized new continuous ambulatory peritoneal dialysis (CAPD) patients to one of two groups. One group used 4 exchanges of standard PD (SPD) solution (Dianeal: Baxter Healthcare BV, Utrecht, Netherlands) daily. The second group used 1 exchange of Nutrineal (Baxter Healthcare BV), 1 exchange of Extraneal (Baxter Healthcare BV), and 2 exchanges of Physioneal (Baxter Healthcare BV) daily (NEPP). After 30 weeks of treatment, each group switched over to the other regimen for 24 weeks. Statistical analysis used analysis of variance (ANOVA) for repeated measurements. Of the 74 patients enrolled into the study, 50 completed the full study period (24 NEPP-SPD, 26 SPD-NEPP). With regard to daily ultrafiltration and dialysis efficacy (Kt/V), the NEPP regimen was as efficacious as the standard regimen. The NEPP regimen was found to be safe: body weight, blood pressure, decline in urine volume, residual creatinine clearance, and laboratory measurements did not differ statistically significantly from those measured in the standard regimen. The NEPP regimen was well tolerated and was not accompanied by serious side effects. During the NEPP regimen, bicarbonate was found to be significantly higher in both groups. The NEPP regimen is a feasible treatment schedule for patients starting CAPD.

Topics: Amino Acids; Blood Pressure; Body Weight; Creatinine; Cross-Over Studies; Dialysis Solutions; Female; Glucans; Glucose; Hemodialysis Solutions; Humans; Icodextrin; Male; Middle Aged; Organic Chemicals; Peritoneal Dialysis, Continuous Ambulatory; Peritoneum; Peritonitis; Ultrafiltration

Overhydration is a risk factor for hypertension and left ventricular hypertrophy in peritoneal dialysis patients. Recently, a high prevalence of subclinical overhydration was observed in peritoneal dialysis patients. Aim of the present open-label randomized study was to assess the effect of a icodextrin 7.5% solution on fluid status [extracellular water (ECW) bromide dilution], blood pressure regulation (24-hour ambulatory measurements) and echocardiographic parameters during a study period of 4 months, and to relate the effect to peritoneal membrane characteristics (dialysate/plasma creatinine ratio). Forty peritoneal dialysis patients (22 treated with icodextrin, 18 controls) were randomized to either treatment with icodextrin during the long dwell or standard glucose solutions. Thirty-two patients (19 treated with icodextrin, 13 controls] completed the study. The use of icodextrin resulted in a significant increase in daily ultrafiltration volume (744 +/- 767 mL vs. 1670 +/- 1038 mL; P = 0.012) and a decrease in ECW (17.5 +/- 5.2 L vs. 15.8 +/- 3.8 L; P = 0.035). Also the change in ECW between controls and patients treated with icodextrin was significant (-1.7 +/- 3.3 L vs. +0.9 +/- 2.2 L; P = 0.013). The effect of icodextrin on ECW was not related to peritoneal membrane characteristics, but significantly related to the fluid state of the patients (ECW:height) (r = -0.72; P < 0.0001). Left ventricular mass (LVM) decreased significantly in the icodextrin-treated group (241 +/- 53 grams vs. 228 +/- 42 grams; P = 0.03), but not in the control group. In this randomized open-label study, the use of icodextrin resulted in a significant reduction in ECW and LVM. The effect of icodextrin on ECW was not related to peritoneal membrane characteristics, but was related to the initial fluid state of the patient.

Topics: Adult; Aged; Blood Pressure; Blood Volume; Body Composition; Body Weight; Dialysis Solutions; Diuresis; Echocardiography; Female; Glomerular Filtration Rate; Glucans; Glucose; Humans; Icodextrin; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis; Peritoneum; Water-Electrolyte Balance

This article presents the results of two randomized, double-blind, controlled studies conducted to compare the efficacy and long-term safety of icodextrin and 2.5% dextrose for the once-daily long dwell in continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD).. Both studies were active-control comparisons of 7.5% icodextrin and 2.5% dextrose for the once-daily long dwell. The efficacy study was a 4-week evaluation of net ultrafiltration and peritoneal clearances of creatinine and urea nitrogen in 175 CAPD patients. The 52-week study in CAPD and APD patients examined the long-term safety of icodextrin and longer term effects, such as body weight and quality of life.. Mean net ultrafiltration (587.2 versus 346.2 mL, P < 0.001) and clearances of urea nitrogen (4.5 versus 4.1 mL/min, P < 0.001) and creatinine (4.0 versus 3.5 mL/min, P < 0.001) were increased significantly with icodextrin. Patients receiving icodextrin had no increase in weight after 52 weeks, in contrast to a weight gain of almost 2 kg in the dextrose group (P < 0.05). There were significantly fewer patients reporting edema in the icodextrin group compared with the dextrose group (6.3% versus 17.9%, P < 0.01). There were no statistically significant differences between groups for the incidence and severity of adverse events. There were small decreases in sodium and chloride and increases in alkaline phosphatase with icodextrin.. Icodextrin provides patients with greater fluid removal and small solute clearance, no weight gain over 52 weeks, and a decreased risk of edema.

Topics: Adult; Aged; Aged, 80 and over; Blood Urea Nitrogen; Body Weight; Creatinine; Double-Blind Method; Female; Glucans; Glucose; Hemodialysis Solutions; Humans; Icodextrin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Quality of Life; Treatment Outcome; Ultrafiltration

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.

Topics: Absorption; Adult; Aged; Blood Pressure; Body Weight; Female; Glucans; Glucose; Humans; Icodextrin; Kidney Function Tests; Male; Middle Aged; Peritoneal Dialysis; Prospective Studies; Sodium; Ultrafiltration

Glucose absorption from glucose-based dialysis fluids limits ultrafiltration from the daytime dwell in automated peritoneal dialysis (APD). Icodextrin may allow greater ultrafiltration during the daytime period in APD, enhancing fluid control.. A 7.5% icodextrin dialysate was compared with a 2. 27% glucose dialysate for the daytime dwell in 14 subjects on APD. Blood pressure, weight and body water compartments estimated by multifrequency bioelectrical impedance (MFBIA) were determined in subjects using 2.27% glucose as the daytime dwell and then repeated 1 month after switching to icodextrin.. Icodextrin resulted in symptomatic hypotension requiring reduction of antihypertensive medication in six of the 14 patients. Despite this reduction in treatment, systolic blood pressure fell from 142.4 (23.9) mmHg to 122.9 (17.7) mmHg, P<0.005, and diastolic blood pressure tended to fall from 82.8 (9.8) mmHg to 76.8 (10.1) mmHg, P=0.075. Change in systolic blood pressure significantly correlated with changes in weight (r=0.62, P<0.05) and MFBIA estimates of total body water (TBW) (r=0.56, P<0.05), extracellular water (ECW) (r=0.79, P<0.002), extra/intracellular water ratio (ECW/ICW) (r=0.72, P<0.01) and derived resistances R(ecf) of ECW (r=-0.69, P<0.01) and R(inf) of TBW (r=-0.66, P<0.02). Changes in diastolic blood pressure significantly correlated with changes in ECW (r=0.64, P<0.02) and ECW/ICW ratio (r=0.58, P<0.05), and almost significantly with R(ecf) (r=-0.51, P=0.08) and R(inf) (r=-0.52, P=0.07) estimated by MFBIA, but not with changes in weight or TBW.. Use of icodextrin for the daytime dwell in APD results in improved fluid balance and blood pressure control compared with 2.27% glucose. MFBIA detected clinically important changes in fluid content in these patients.

Topics: Adult; Aged; Antihypertensive Agents; Automation; Blood Pressure; Body Composition; Body Weight; Dialysis Solutions; Electric Impedance; Female; Glucans; Glucose; Humans; Icodextrin; Male; Middle Aged; Peritoneal Dialysis; Regression Analysis; Systole

The purpose of this study was to analyse the changes of body composition and the effects of icodextrin dialysis solution over time on peritoneal dialysis (PD) in continuous ambulatory peritoneal dialysis (CAPD) patients.. Among 183 incident patients, 75 patients finished a complete 36-month protocol. Clinical indices including daily glucose absorption and body composition, by bioelectrical impedance analysis (BIA), were measured in both groups (icodextrin group: 36 patients, non-icodextrin group: 39 patients) at the 1st (baseline), 12th, 24th and 36th months.. There were significant increases in body weight and fat mass during the 36 months after initiation of CAPD. It was found that 78% of 3 years of weight gain occurred during the first year and 88% of weight gain at the end of the first year was fat mass gain. The icodextrin group showed a significantly lower percent of fat mass during the first 36 months (P < 0.05) and also less changes in body weight, fat mass, percent (%) fat mass, visceral fat area and waist/hip ratio at 1, 2 and 3 years than the non-icodextrin group. There were no significant changes in total body water (TBW), extra cellular fluid (ECF), oedema index and lean body mass (LBM) through comparable daily and ultrafiltration volume (UFV) between the two groups during the initial 3 years. Factors associated with the higher percent of fat mass gain over time on peritoneal dialysis were age, diabetes, gender (female) and non-icodextrin group (all, P < 0.01, generalized estimating equation).. The application of icodextrin solution may be a better option to alleviate excessive fat gain over time for patients on PD.

Topics: Adult; Body Composition; Body Fat Distribution; Body Weight; Dialysis Solutions; Female; Glucans; Glucose; Humans; Icodextrin; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Time Factors

To evaluate and compare the effects of glucose-based solutions to those of icodextrin with respect to peritoneal transport characteristics and formation of advanced glycosylation end-products (AGEs) in the peritoneal membrane in the diabetic rat model of peritoneal dialysis (PD).. Thirty-three male Sprague-Dawley rats weighing between 275 - 300 g were divided into 5 groups: group C (n = 6), control rats with catheter but not dialyzed; group D (n = 5), diabetic rats with catheter but not dialyzed; group G (n = 7), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 4.25% glucose solution for the overnight exchange; group H (n = 8), diabetic rats dialyzed with standard 2.5% glucose solution for daytime exchanges and 7.5% icodextrin solution for overnight exchanges; group I (n = 7), diabetic rats dialyzed with 7.5% icodextrin solution for all exchanges. Dialysis exchanges were performed three times daily with an instillation volume of 25 mL per exchange for a period of 12 weeks. Tissue sections were stained using a monoclonal anti-AGE antibody. One-hour peritoneal equilibration tests (PET) were performed every 4 weeks for comparison of transport characteristics.. The level of immunostaining was lowest in group C and highest in group G. Significant differences were seen between group C and groups G, H, and I (p < 0.001, p = 0.001, and p< 0.05 respectively). Significant differences were also found between group G and groups D and I (p < 0.05 and p < 0.05 respectively). Over time, glucose concentration at the end of an exchange versus concentration at instillation (D/D0 glucose) decreased and dialysate-to-plasma ratio (D/P) of urea increased. Significant differences were found between groups C and H for D/D0 glucose (0.40+/-0.01 vs 0.35+/-0.01, p < 0.05); and between groups C and H for D/P urea (0.87+/-0.03 vs 0.97+/-0.02, p < 0.05).. These results suggest that AGE formation is lower with the use of peritoneal dialysis solution containing icodextrin than with glucose-based solutions. We conclude that the use of icodextrin may be helpful in slowing the deterioration of the peritoneal membrane, prolonging its use for dialysis.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Dialysis Solutions; Glucans; Glucose; Glycation End Products, Advanced; Icodextrin; Male; Peritoneal Dialysis; Peritoneum; Rats; Rats, Sprague-Dawley