scholarly journals Optimization of bimodal automated peritoneal dialysis prescription using the three-pore model

2021 ◽  
pp. 089686082110100
Author(s):  
Carl M Öberg

Background: Previous studies suggested that automated peritoneal dialysis (APD) could be improved in terms of shorter treatment times and lower glucose absorption using bimodal treatment regimens, having ‘ultrafiltration (UF) cycles’ using a high glucose concentration and ‘clearance cycles’ using low or no glucose. The purpose of this study is to explore such regimes further using mathematical optimization techniques based on the three-pore model. Methods: A linear model with constraints is applied to find the shortest possible treatment time given a set of clinical treatment goals. For bimodal regimes, an exact analytical solution often exists which is herein used to construct optimal regimes giving the same Kt/ V urea and/or weekly creatinine clearance and UF as a 6 × 2 L 1.36% glucose regime and an ‘adapted’ (2 × 1.5 L 1.36% + 3 × 3 L 1.36%) regime. Results: Compared to the non-optimized (standard and adapted regimes), the optimized regimens demonstrated marked reductions (>40%) in glucose absorption while having an identical weekly creatinine clearance (35 L) and UF (0.5 L). Larger fill volumes of 1200 mL/m2 (UF cycles) and 1400 mL/m2 (clearance cycles) can be used to shorten the total treatment time. Conclusion: These theoretical results imply substantial improvements in glucose absorption using optimized APD regimens while achieving similar water and solute removal as non-optimized APD regimens. While the current results are based on a well-established theoretical model for peritoneal dialysis, experimental and clinical studies need to be performed to validate the current findings.

2011 ◽  
Vol 31 (5) ◽  
pp. 537-544 ◽  
Author(s):  
Alp Akonur ◽  
J. Ken Leypoldt

BackgroundRecently, bimodal peritoneal dialysis (PD) solutions containing low concentrations of Na have been shown to increase 24-hour ultrafiltration (UF) or UF efficiency (UF volume per gram of carbohydrate or CHO absorbed) and Na removal in high (“fast”) transport patients during automated PD therapy. We used computer simulations to compare UF efficiency and Na removal at equivalent 24-hour UF volumes using either a generic bimodal solution (2.27% glucose + 7.5% icodextrin) during the long dwell or an increase in the glucose concentration during the short dwells, with all solutions containing Na at the conventional concentration (132 mEq/L).MethodsThe 3-pore model has been shown to accurately predict peritoneal transport for PD solutions containing glucose or icodextrin, or both. Here, we used that model to calculate 24-hour UF volume, CHO absorption, and Na removal for high (H), high-average (HA), and low-average (LA) transport patients on automated PD. Nighttime therapy consisted of 1.36% or 2.27% glucose solution (or both), and daytime therapy consisted of either Extraneal (Baxter Healthcare Corporation, Deerfield, IL, USA) or a bimodal solution.ResultsAs expected, addition of glucose to either the long dwell or the short dwells resulted in increased UF volume and glucose absorption. The increase in UF was a function of patient transport type (bimodal range: 288 – 490 mL; short-dwell range: 323 – 350 mL), and the increase in CHO absorption was smaller with glucose added to short dwells than with bimodal solution (range: 18 – 30 g vs. 34 – 39 g). The 24-hour UF efficiency was higher when high glucose concentrations were used during short-dwell exchanges than when a bimodal PD solution was used for the long dwell (0.6 to 1.2 mL/g vs. –0.1 to 0.5 mL/g). By contrast, Na removal was lower with the short-dwell exchanges (28.3 – 30.7 mmol vs. 36.2 – 53.3 mmol), likely because of more pronounced Na sieving.ConclusionsOur modeling studies predict that generic bimodal PD solutions will provide higher Na removal but not higher 24-hour UF efficiency compared with current automated PD prescriptions using Extraneal for the long dwell and glucose-containing solutions for the short dwells. The modeling predictions from this study require clinical validation.


2020 ◽  
Author(s):  
Karin Bergling ◽  
Javier de Arteaga ◽  
Fabián Ledesma ◽  
Carl Mikael Öberg

Abstract Background: It has been estimated that automated peritoneal dialysis (APD) is currently the fastest growing renal replacement therapy in the world. However, in light of the growing number of diabetic patients on peritoneal dialysis (PD), the unwanted glucose absorption during APD remains problematic. Recent results, using an extended 3-pore model of APD, indicated that large reductions in glucose absorption are possible by using optimized bi-modal treatment regimens, having “UF cycles” using a higher glucose concentration and “Clearance cycles” using a low concentration or, preferentially, no glucose. The present study is designed to test the theoretical prediction of a lower glucose absorption using these novel regimes. Methods: This study is a randomized single-center, open-label, prospective study. Prevalent PD patients between 18 to 75 years old without known catheter problems or recent peritonitis are eligible for inclusion. Patients are allocated to a first treatment session of either Standard APD (6 × 2 L 1.36% over 9 hours) or Optimized APD (7 × 2 L 2.27% + 5 × 2 L 0.1% over 8 hours). A second treatment session using the other treatment will be performed in a crossover fashion. Samples of the dialysis fluid will be taken before and after the treatment and the volume of the dialysate before and after the treatment will be carefully assessed. The primary endpoint is difference in glucose absorption between the Optimized and Standard treatment. Secondary endpoints are ultrafiltration, sodium removal, Kt/V urea and Kt/V Creatinine. The study will be closed when a total of 20 patients have successfully completed the interventions or terminated according to interim analysis. A Monte Carlo power analysis shows that the study has 80% power to detect a difference of 10 g (in line with that of theoretical results) in glucose absorption between the two treatments in 10 patients. Discussion: The present study is the first clinical investigation of optimized bi-modal treatments proposed by recent theoretical studies.


1996 ◽  
Vol 16 (1_suppl) ◽  
pp. 167-171 ◽  
Author(s):  
Pierre Yves Durand ◽  
Philippe Freida ◽  
Belkacem Issad ◽  
Jacques Chanliau

This paper summarizes the basis of prescription for automated peritoneal dialysis (APD) established during a French national conference on APD. Clinical results and literature data show that peritoneal clearances are closely determined by peritoneal permeability and hourly dialysate flow rate, independently of dwell time or number of cycles. With APD, peritoneal creatinine clearance increases according to the hourly dialysate flow rate to a maximum (plateau), then decreases because of the multiplication of the drain-fill times. The hourly dialysate flow giving the maximum peritoneal creatinine clearance is defined as the “maximal effective dialysate flow” (MEDF). MEDF is higher for high peritoneal permeabilities: MEDF is 1.8 and 4.2 L/hr with nocturnal tidal peritoneal dialysis (TPD) for a 4-hr creatinine dialysate-to-plasma ratio (DIP) of 0.50 and 0.80, respectively. With nightly intermittent peritoneal dialysis (NIPD), MEDF is 1.6 and 2.3 Llhr for a DIP of 0.50 and 0.78, respectively. Under these conditions, tidal modalities can only be considered as a way to increase the MEDF. Using the MEDF concept for an identical APD session duration, the maximal weekly normalized peritoneal creatinine clearance can vary by 340% when 4hr DIP varies from 0.41 to 0.78. APD is not recommended when 4-hr creatinine DIP is lower than 0.50. However, the limits of this technique may be reached at higher peritoneal permeabilities in anurics because of the duration of sessions andlor the additional exchanges required by these patients.


1996 ◽  
Vol 16 (3) ◽  
pp. 307-315 ◽  
Author(s):  
Kinya Hiroshige ◽  
Kougi Yuu ◽  
Masasuke Soejima ◽  
Masayuki Takasugi ◽  
Akio Kuroiwa

Objective To determine the effect of peritoneal dialysis modalities such as nightly intermittent peritoneal dialysis (NIPD), continuous cyclic peritoneal dialysis (CCPD), and continuous ambulatory peritoneal dialysis (CAPD) on residual renal function. Design A six-month prospective, nonrandomized comparison study. Setting Outpatient CAPD unit of a university hospital. Participants Eighteen end-stage renal disease patients treated by peritoneal dialysis (8 by NIPD, 5 by CCPD, and 5 by CAPD). Interventions Samples from the total dialysate, blood, and 24hour urine collection were obtained monthly. Measurements Urea, creatinine, and beta2-microglobulin concentrations were measured. Renal and peritoneal clearances of each substance and KT/V urea were calculated. Residual renal function (RRF) was estimated by renal creatinine clearance (RCcr). Results No significant differences in age, sex, and primary renal disease among the three groups were noted. In all groups, anemic and hypertensive states were controlled identically, and mean weekly total (renal + peritoneal) KT/V urea (over 2.1/wk) and total creatinine clearance (over 60 L/wk/1.73 m2) were maintained during the whole experimental period. Starting mean RCcr was near 4.0 mL/min/1.73 m2 in all groups. Thereafter, a rapid and significant decline in RRF was demonstrated on NIPD and CCPD. The declining rates of RCcr values at 6 months after starting NIPD and CCPD were -0.29 and -0.34 mL/min/month, respectively, which were much greater than those of CAPD (+0.01 mL/min/month). Conclusion Because of a possibly characteristic progressive loss of RRF in automated peritoneal dialysis (APD), strict regular assessment of RRF should be performed from the start of APD.


2001 ◽  
Vol 21 (3_suppl) ◽  
pp. 133-137 ◽  
Author(s):  
Edwina A. Brown ◽  
Simon J. Davies ◽  
Olof Heimbürger ◽  
Frederique Meeus ◽  
George Mellotte ◽  
...  

♦ Objective Conventional continuous ambulatory peritoneal dialysis (CAPD) in patients without residual renal function and with high solute transport is associated with worse clinical outcomes. Automated peritoneal dialysis (APD) has the potential to improve both solute clearance and ultrafiltration in these circumstances, but its efficacy as a treatment modality is unknown. The European Automated Peritoneal Dialysis Outcomes Study (EAPOS) is a 2-year, prospective, European multi-center study designed to determine APD feasibility and clinical outcomes in anuric patients. The present article describes the baseline data for patients recruited into the study. ♦ Design All PD patients treated in the participating centers were screened for inclusion criteria [urinary output < 100 mL/24 h, or residual renal function (RRF) < 1 mL/min, or both]. After enrollment, changes were made to the dialysis prescription to achieve a weekly creatinine clearance above 60 L per 1.73 m2 and an ultrafiltration rate above 750 mL in 24 hours. ♦ Setting The study is being conducted in 26 dialysis centers in 13 European countries. ♦ Baseline Data Collection The information collected includes patient demographics, dialysis prescription, achieved weekly creatinine clearance, and 24-hour ultra-filtration (UF). ♦ Results The study enrolled 177 anuric patients. Median dialysis duration before enrollment was 22.5 months (range: 0 – 285 months). Mean solute transport measured as the dialysate-to-plasma ratio of creatinine (D/PCr) was 0.74 ± 0.12. Patients received APD for a median of 9.0 hours overnight (range: 7 – 12 hours) using a median of 11.0 L of fluid (range: 6 – 28.75 L). Median daytime volume was 4.0 L (range: 0.0 – 9.0 L). Tidal dialysis was used in 26 patients, and icodextrin in 86 patients. At baseline, before treatment optimization, the weekly mean total creatinine clearance was 65.2 ± 14.4 L/1.73 m2, with 105 patients (60%) achieving the target of more than 60 L/1.73 m2. At baseline, 81% of patients with high transport, 69% with high-average transport, and 40% with low-average transport met the target. At baseline, 70% of patients with a body surface area (BSA) below 1.7 m2, 60% with a BSA of 1.7 – 2.0 m2, and 56% with a BSA above 2.0 m2 achieved 60 L/1.73 m2 weekly. Median UF was 1090 mL/24 h, and 75% of patients achieved the UF target of more than 750 mL/24 h. ♦ Conclusion This baseline analysis of anuric patients recruited into the EAPOS study demonstrates that a high proportion of anuric patients on APD can achieve dialysis and ultrafiltration targets using a variety of regimes. This 2-year follow-up study aims to optimize APD prescription to reach predefined clearance and ultrafiltration targets, and to observe the resulting clinical outcomes.


2000 ◽  
Vol 20 (5) ◽  
pp. 548-556 ◽  
Author(s):  
Rafael A. Perez ◽  
Peter G. Blake ◽  
Susan McMurray ◽  
Lou Mupas ◽  
Dimitrios G. Oreopoulos

Objective The recent increase in the use of automated peritoneal dialysis (APD) has led to concerns about the adequacy of clearances delivered by this modality. Few clinical studies looking at the effects of varying the individual components of the APD prescription on delivered clearance have been done, and most published data are derived from computer modeling. Most controversial is the optimal frequency of exchanges per APD session. Many centers prescribe 4 to 6 cycles per night but it is unclear if this is optimal. The purpose of this study was to address at what point the beneficial effect of more frequent cycles is outweighed by the concomitant increase in the proportion of the total cycling time spent draining and filling. Methods A comparison was made between the urea and creatinine clearances (CCrs) achieved by 4 different APD prescriptions, used for 7 days each, in 18 patients. The prescriptions were for 9 hours each and were all based on 2-L dwell volumes, but differed in the frequency of exchanges. They were 5 x 2 L, 7 x 2 L, and 9 x 2 L, as well as a 50% tidal peritoneal dialysis (TPD) prescription using 14 L. Ultrafiltration, dwell time, glucose absorption, sodium and potassium removal, protein excretion, and relative cost were also compared. Clearances due to day dwells and residual renal function were not included in the calculation. Results Mean urea clearances were 7.5, 8.6, 9.1, and 8.3 L/night for the four prescriptions respectively. Urea clearance with 9 x 2 L was significantly greater than with the other three prescriptions ( p < 0 0.05). Urea clearance with 7 x 2 L and TPD were superior to 5 x 2 L ( p < 0.05). Mean CCr was 5.1, 6.1, 6.4, and 5.6 L/night, respectively. Compared to 5 x 2-L, the 7 x 2-L, 9 x 2-L, and TPD prescriptions achieved greater CCr ( p < 0.05). Taking both urea and CCr into account, 9 x 2 L was the optimal prescription in 12 of the 18 patients. Ultrafiltration and sodium and potassium removals were all significantly greater with the higher frequency prescriptions. Conclusion The 5 x 2-L prescription significantly underutilizes the potential of APD to deliver high clearances, and 7 x 2 L is a consistently superior prescription if 2-L dwells are being used. Although more costly, 9 x 2 L should be considered if higher clearances are required.


2020 ◽  
Vol 43 (7) ◽  
pp. 461-467
Author(s):  
Theerasak Tangwonglert ◽  
Andrew Davenport

Background and aims: Glucose-containing peritoneal dialysates are used to generate an osmotic gradient for the convective removal of water and sodium. Predictive equations were developed to estimate glucose absorption without having to formally measure changes in dialysate glucose. In view of the changes in peritoneal dialysis prescriptions over time, we compared predicted and measured glucose absorption. Subjects/methods: We measured peritoneal glucose losses when peritoneal dialysis patients attended their first assessment of peritoneal membrane function, and compared this to glucose exposure and Kidney Disease Outcomes Quality Initiative, Grodstein and Bodnar predictive equations. Results: We studied 689 patients; 329 (56.9%) males, 53 (37.1%) diabetics, with mean age 57.1 ± 16.2 years, with 186 treated by automated peritoneal dialysis cyclers and 377 by automated peritoneal dialysis with a daytime icodextrin exchange and 126 by continuous ambulatory peritoneal dialysis. Using Bland -Altman analysis, all equations demonstrated systematic bias overestimating glucose absorption with increasing glucose absorption. For continuous ambulatory peritoneal dialysis patients, the Kidney Disease Outcomes Quality Initiative formula underestimated glucose absorption (bias 188 (−39 to 437) mmol/day, as did Grodstein (bias 37.9 (−105 to 29) mmol/day, whereas mean bias for Bodnar was −29 (−130 to 180)). There was systematic overestimation for all equations for both automated peritoneal dialysis with and without a daytime exchange, with increasing bias with greater glucose absorption. Conclusion: Although formally measuring peritoneal glucose absorption is time consuming and requires patient co-operation, current predictive equations overestimate glucose absorption and do not provide accurate estimations of glucose absorption particularly for automated peritoneal dialysis patients.


2016 ◽  
Vol 42 (4) ◽  
pp. 287-293 ◽  
Author(s):  
Alessandro Domenici ◽  
Anna Giuliani ◽  
Francesca Sivo ◽  
Clorinda Falcone ◽  
Giorgio Punzo ◽  
...  

This study compares 5 different tidal automated peritoneal dialysis (APD) prescriptions. Six low-average and 6 high-average transporters performed 3 separate sessions with 5 different schedules: (A) 50% tidal with initial fill volume (FV) 2 liters, (B) 50% tidal with 2.2 liters initial FV, (C) 2.2 liters initial FV with 70% tidal, (D) as in B, with one complete renewal of the initial FV at midsession, (E) 2.2 liters FV with breakpoint modality. Urea, creatinine and phosphate peritoneal clearances, sodium removal and ultrafiltration (UF) were compared using analysis of variance. Compared to treatment A, all the tested alternative schedules were associated with 10% significantly higher urea clearance; B, D and E, but not C, were associated with 10% higher creatinine clearance. Phosphate clearance was significantly higher with D, while sodium removal was larger with both C and D. UF was lower with A and E in high average transporters. Manipulation of the main prescriptive parameters of tidal APD has significant impact on its efficiency.


2020 ◽  
Author(s):  
Karin Bergling ◽  
Javier de Arteaga ◽  
Fabián Ledesma ◽  
Carl Mikael Öberg

Abstract Background: It has been estimated that automated peritoneal dialysis (APD) is currently the fastest growing renal replacement therapy in the world. However, in light of the growing number of diabetic patients on peritoneal dialysis (PD), the unwanted glucose absorption during APD remains problematic. Recent results, using an extended 3-pore model of APD, indicated that large reductions in glucose absorption are possible by using optimized bi-modal treatment regimens, having “UF cycles” using a higher glucose concentration and “Clearance cycles” using a low concentration or, preferentially, no glucose. The present study is designed to test the theoretical prediction of a lower glucose absorption using these novel regimes.Methods: This study is a randomized single-center, open-label, prospective study. Prevalent PD patients between 18 to 75 years old without known catheter problems or recent peritonitis are eligible for inclusion. Patients are allocated to a first treatment session of either Standard APD (6 × 2 L 1.36% over 9 hours) or Optimized APD (7 × 2 L 2.27% + 5 × 2 L 0.1% over 8 hours). A second treatment session using the other treatment will be performed in a crossover fashion. Samples of the dialysis fluid will be taken before and after the treatment and the volume of the dialysate before and after the treatment will be carefully assessed. The primary endpoint is difference in glucose absorption between the Optimized and Standard treatment. Secondary endpoints are ultrafiltration, sodium removal, Kt/V urea and Kt/V Creatinine. The study will be closed when a total of 20 patients have successfully completed the interventions or terminated according to interim analysis. A Monte Carlo power analysis shows that the study has 80% power to detect a difference of 10 g (in line with that of theoretical results) in glucose absorption between the two treatments in 10 patients.Discussion: The present study is the first clinical investigation of optimized bi-modal treatments proposed by recent theoretical studies.Trial registration: ClinicalTrials.gov identifier: NCT04017572. Registration date: 12/07/2019, retrospectively registered. URL: https://clinicaltrials.gov/ct2/show/NCT04017572


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