A combined crystalloid and colloid pd solution as a glucose-sparing strategy for volume control in high-transport apd patients: a prospective multicenter study.

BACKGROUND: Evidence is accumulating that the continuous exposure to high glucose concentrations during peritoneal dialysis (PD) is an important cause of ultrafiltration (UF) failure. The cornerstone of prevention and treatment of UF failure is reduction of glucose exposure, which will also alleviate the systemic impact of significant free glucose absorption. The challenge for the future is to discover new therapeutic strategies to enhance fluid and sodium removal while diminishing glucose load and exposure using combinations of available osmotic agents. OBJECTIVES: To investigate in patients on automated PD (APD) with a fast transport pattern whether there is a glucose-sparing advantage to replacing 7.5% icodextrin (ICO) during the long dwell with a mixed crystalloid and colloid PD fluid (bimodal UF) in an attempt to promote daytime UF and sodium removal while diminishing the glucose strength of the dialysate at night. DESIGN: A 2 parallel arm, 4 month, prospective nonrandomized study. SETTING: PD units or university hospitals in 4 French and Belgian districts. RESULTS: During the 4-month intervention period, net UF and peritoneal sodium removal during the long dwell when treated by bimodal UF was about 2-fold higher than baseline (with ICO). The estimated percent change (95% confidence interval) from baseline in net daytime UF for the bimodal solution was 150% (106% - 193%), versus 18% (-7% - 43%) for ICO (p < 0.001). The estimated percent change from baseline in peritoneal sodium removal for the bimodal solution was 147% (112% - 183%), versus 23% (-2% - 48%) for ICO (p < 0.001). The estimated percent change from baseline in UF efficiency (24-hour net UF divided by the amount of glucose absorbed) was significantly higher (p < 0.001) when using the bimodal solution was 71%, versus -5% for ICO. CONCLUSION: Prescription of bimodal UF during the day in APD patients offers the opportunity to optimize the long dwell exchange in a complete 24-hour APD cycle. The current study demonstrated that a bimodal solution based on the mixing of glucose (2.6%) and icodextrin (6.8%) achieved the double target of significantly improving UF and peritoneal sodium removal by exploring a new concept of glucose-sparing PD therapy.

Kinetic analysis of peritoneal fluid and solute transport with combination of glucose and icodextrin as osmotic agents.

BACKGROUND: Controlling extracellular volume and plasma sodium concentration are two crucial objectives of dialysis therapy, as inadequate sodium and fluid removal by dialysis may result in extracellular volume overload, hypertension, and increased cardiovascular morbidity and mortality in end-stage renal disease patients. A new concept to enhance sodium and fluid removal during peritoneal dialysis (PD) is the use of dialysis solutions with two different osmotic agents. AIM: To investigate and compare, with the help of mathematical modeling and computer simulations, fluid and solute transport during PD with conventional dialysis fluids (3.86% glucose and 7.5% icodextrin; both with standard sodium concentration) and a new combination fluid with both icodextrin and glucose (CIG; 2.6% glucose/6.8% icodextrin; low sodium concentration). In particular, this paper is devoted to improving mathematical modeling based on critical appraisal of the ability of the original three-pore model to reproduce clinical data and check its validity across different types of osmotic agents. METHODS: Theoretical investigations of possible causes of the improved fluid and sodium removal during PD with the combination solution (CIG) were carried out using the three-pore model. The results of computer simulations were compared with clinical data from dwell studies in 7 PD patients. To fit the model to the low net ultrafiltration (366+/-234 mL) obtained after a 4-hour dwell with 3.86% glucose, some of the original parameters proposed in the three-pore model (Rippe & Levin. Kidney Int 2000; 57:2546-56) had to be modified. In particular, the aquaporin-mediated fractional contribution to hydraulic permeability was decreased by 25% and small pore radius increased by 18%. RESULTS: The simulations described well clinical data that showed a dramatic increase in ultrafiltration and sodium removal with the CIG fluid in comparison with the two other dialysis fluids. However, to adapt the three-pore model to the selected group of PD patients (fast transporters with small ultrafiltration capacity on average), the peritoneal pore structure had to be modified. As the mathematical model was capable of reproducing the clinical data, this shows that the enhanced ultrafiltration with the combination fluid is caused by the additive effect of the two different osmotic agents and not by a specific impact of the new dialysis fluid on the transport characteristics of the peritoneum.

Combination of crystalloid (glucose) and colloid (icodextrin) osmotic agents markedly enhances peritoneal fluid and solute transport during the long PD dwell.

BACKGROUND: Fluid and sodium removal is often inadequate in peritoneal dialysis patients with high peritoneal solute transport rate, especially when residual renal function is declining. METHOD: We studied the effects of using simultaneous crystalloid (glucose) and colloid (icodextrin) osmotic agents on the peritoneal transport of fluid, sodium, and other solutes during 15-hour single-dwell exchanges using 3.86% glucose, 7.5% icodextrin, and a combination fluid with 2.61% glucose and 6.8% icodextrin in 7 prevalent peritoneal dialysis patients with fast peritoneal solute transport rate. RESULTS: The combination fluid enhanced net ultrafiltration (mean 990 mL) and sodium removal (mean 158 mmol) compared with 7.5% icodextrin (mean net ultrafiltration 462 mL, mean net sodium removal 49 mmol). In contrast, the 3.86% glucose-based solution yielded negligible ultrafiltration (mean -85 mL) and sodium removal (mean 16 mmol). The combination solution resulted in significantly improved urea (+41%) and creatinine (+26%) clearances compared with 7.5% icodextrin. CONCLUSION: A solution containing both crystalloid (glucose 2.61%) and colloid (icodextrin 6.8%) osmotic agents enhanced fluid removal by twofold and sodium removal by threefold compared with 7.5% icodextrin solution during a dwell of 15 hours, indicating that such a combination solution could represent a new treatment option for anuric peritoneal dialysis patients with high peritoneal solute transport rate.

Continuous flow peritoneal dialysis: assessment of fluid and solute removal in a high-flow model of "fresh dialysate single pass".

BACKGROUND: Growing concern over the limited capacity of the peritoneal dialysis (PD) system has revived interest in continuous flow peritoneal dialysis (CFPD), a modality in which continuous circulation of PD fluid is maintained at a high flow rate using two separate catheters or one dual-lumen catheter. The CFPD regimen contrasts the "inflow/outflow" regimen, which requires specific times devoted to filling and draining the peritoneum via a single-lumen catheter. Historical data established CFPD capabilities in providing higher solute clearance and ultrafiltration rate (UFR) using either an open loop system with a single pass of fresh PD fluid, or various external purifications of the spent dialysate. OBJECTIVE: To compare, in patients with various peritoneal transport patterns, fluid and solute removal achieved during a standardized program of CFPD versus two control schedules: nightly intermittent peritoneal dialysis (NIPD) and nightly tidal peritoneal dialysis (NTPD). This study focused on small solute clearances and UFR using only isotonic PD solution (Dianeal PD1 1.36%; Baxter Healthcare, Castlebar, Ireland). The model of fresh dialysate, single pass, was used to optimize solute gradients and to characterize the impact of a continuous flow regimen on peritoneal transport characteristics. METHODS: In a crossover trial, 4-hour CFPD sessions were performed at a fixed dialysate flow rate (100 mL/ minute) in 5 patients being treated with automated PD. A hemofiltration monitor (BM25; Baxter Healthcare, Brussels, Belgium) was adapted to the CFPD technique. The peritoneal cavity was filled through a temporary second catheter and simultaneously drained using the permanent peritoneal access. Fluid and solute removal were compared to data obtained from a control period based on 8-hour sessions of NIPD or NTPD using 13 L of isotonic dialysate. RESULTS: High-flow CFPD enhanced the diffusive transport coefficient compared with the alternative flow regimen in patients ranging from low to high transporters. Weekly creatinine clearance increased from 36.9 L (22.3 - 49.6 L) and 37.3 L (27.5 - 45.0 L) with NIPD and NTPD respectively, to 74.9 L (42.3 - 107.5 L) with CFPD. Mean UFR was 2.44 mL/min with CFPD versus 0.92 and 0.89 mL/min with NIPD and NTPD respectively. The mass transfer area coefficient (MTAC) of creatinine with CFPD was 2.5-fold that obtained from the peritoneal equilibration test data. CONCLUSION: Our results confirm that CFPD is highly effective in increasing fluid and solute removal. Furthermore, consistent with historical data, our findings indicate that the enhanced solute transfer is not due only to steeper solute gradients, but also depends on increased MTAC in a wide range of peritoneum transport characteristics.

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.