Peritoneal Residual Volume Induces Variability of Ultrafiltration with Icodextrin

Akonur, Alp; Holmes, Clifford J.; Leypoldt, John K.

doi:10.3747/pdi.2012.00175

Cited by 8 publications

(9 citation statements)

References 30 publications

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“…In addition, the UF predictions during 9-and 14-hour exchanges provided here should not be considered as typical UF values obtained during CAPD and APD, respectively. Studies have shown that exchange time alone is not sufficient to describe UF with icodextrin during APD and CAPD (31) and multiple, patient and therapy-specific parameters need to be carefully considered to obtain accurate predictions of UF with icodextrin (27)(28)(29). Finally, our model assumed a constant, time-averaged, amylase concentration in dialysate.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent article, we reviewed a large number studies that measured UF with icodextrin and found an average range of 204 -950 mL across all patients on APD, CAPD, and studied during single exchanges (29). In the same study, we proposed that peritoneal residual volume is an independent source of variability in UF with icodextrin (29). Given these considerations, the UF range predicted with the present model during 9-and 14-hour exchanges is therefore in agreement with these previous measurements.…”

Section: Discussionmentioning

confidence: 99%

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Predicting the Peritoneal Absorption of Icodextrin in Rats and Humans Including the Effect of α–Amylase Activity in Dialysate

2015

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♦ Background: Contrary to ultrafiltration, the three-pore model predictions of icodextrin absorption from the peritoneal cavity have not yet been reported likely, in part, due to difficulties in estimating the degradation of glucosepolymer chains by α-amylase activity in dialysate. We incorporated this degradation process in a modified three-pore model of peritoneal transport to predict ultrafiltration and icodextrin absorption simultaneously in rats and humans. ♦ Methods: Separate three-pore models were constructed for humans and rats. The model for humans was adapted from PD Adequest 2.0 including a clearance term out of the peritoneal cavity to account for the absorption of large molecules to the peritoneal tissues, and considering patients who routinely used icodextrin by establishing steady-state plasma concentrations. The model for rats employed a standard three-pore model in which human kinetic parameters were scaled for a rat based on differences in body weight. Both models described the icodextrin molecular weight (MW) distribution as five distinct MW fractions. First order kinetics was applied using degradation rate constants obtained from previous in-vitro measurements using gel permeation chromatography. Ultrafiltration and absorption were predicted during a 4-hour exchange in rats, and 9 and 14-hour exchanges in humans with slow to fast transport characteristics with and without the effect of amylase activity. ♦ Results: In rats, the icodextrin MW profile shifted towards the low MW fractions due to complete disappearance of the MW fractions greater than 27.5 kDa. Including the effect of amylase activity (60 U/L) resulted in 21.1% increase in ultrafiltration (UF) (7.6 mL vs 6.0 mL) and 7.1% increase in icodextrin absorption (CHO) (62.5% with vs 58.1%). In humans, the shift in MW profile was less pronounced. The fast transport (H) patient absorbed more icodextrin than the slow transport (L) patient during both 14-hour (H: 47.9% vs L: 40.2%) and 9-hour (H: 37.4% vs L: 31.7%) exchanges. While the UF was higher during the longer exchange, it varied modestly among the patient types (14-hour range: 460 -509 mL vs 9-hour range: 382 -389 mL). When averaged over all patients, the increases in UF and CHO during the 14-hour exchange due to amylase activity (7 U/L) were 15% and 1.5%, respectively. ♦ Conclusion: The icodextrin absorption values predicted by the model agreed with those measured in rats and humans to accurately show the increased absorption in rats. Also, the model confirmed the previous suggestions by predicting an increase in UF specific to amylase activity in dialysate, likely due to the added osmolality by the small molecules generated as a result of the degradation process. As expected, this increase was more pronounced in rats than in humans because of higher dialysate concentrations of amylase in rats.Perit Dial Int 2015; 35(3):288-296 www.PDIConnect.com epub ahead of print:

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Predicting the Peritoneal Absorption of Icodextrin in Rats and Humans Including the Effect of α–Amylase Activity in Dialysate

2015

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“…Theoretical work by our group (24) recently demonstrated that large amounts of residual fluid within the peritoneal cavity before a long-dwell exchange using icodextrin solution can substantially reduce UF; however, the differential effect of residual fluid volume on icodextrin or an 18 -19K glucose polymer solution is expected to be small. Third, it should be emphasized that the rabbit model used in the current study is nonuremic; thus, plasma concentrations of urea nitrogen and creatinine are low (that is, within the normal range).…”

Section: Discussionmentioning

confidence: 99%

Low-Polydispersity Glucose Polymers as Osmotic Agents for Peritoneal Dialysis

et al. 2015

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♦ Background: Peritoneal dialysis (PD) solutions containing icodextrin as the osmotic agent have advantages during long dwells. The glucose polymers that constitute icodextrin are a heterogeneous mix of molecules with a polydispersity [ratio of weight-average to number-average molecular weight (Mw/Mn)] of approximately 2.6. The present study evaluates whether modifications in the polydispersity and concentration of glucose polymers can improve ultrafiltration (UF) without an associated increase in carbohydrate absorption (CA). ♦ Methods: Computer simulations using a three-pore model of peritoneal transport during a long dwell in PD patients predict that, in general, compared with 7.5% icodextrin, glucose polymers with a Mw greater than or equal to 7.5 kDa, a polydispersity less than 2.6, and concentrations greater than 7% could achieve higher UF without higher CA. Based on the simulations, we hypothesized that, compared with 7.5% icodextrin, glucose polymers with a Mw of 18 -19 kDa and a polydispersity of 2.0 at 11% concentration could achieve higher UF without a higher CA. We tested this hypothesis in experimental studies using 8-hour dwells in New Zealand White rabbits. In those studies, UF was measured by complete fluid collection, and CA was measured by subtracting the total carbohydrate in the collected fluid from the carbohydrate initially infused. ♦ Results: The UF was higher with 11% 19 kDa glucose polymer than with 7.5% icodextrin (mean ± standard deviation: 89 ± 31 mL vs 49 ± 15 mL; p = 0.004) without higher CA (5.2 ± 0.9 g vs 5.0 ± 0.9 g, p = 0.7). Similar results were seen with the 11% 18 kDa glucose polymer, which, compared with 7.5% icodextrin, resulted in higher UF (mean ± standard deviation: 96 ± 18 mL vs 66 ± 17 mL; p < 0.001) without higher CA (4.8 ± 0.7 g vs 5.2 ± 0.6 g, p = 0.2).

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“…Fourth, we differentiated APD and CAPD therapies only based on dwell times and number of exchanges; all other underlying patient properties were assumed to be the same. For instance, it is likely that APD patients with larger peritoneal residual volume achieve less UF during the long dwell than CAPD patients when using icodextrin (32). It is also possible that variations in plasma albumin and intra-abdominal pressure due to supine and sitting positions could alter ultrafiltration.…”

Section: Discussionmentioning

confidence: 99%

Icodextrin Simplifies Pd Therapy by Equalizing Uf and Sodium Removal among Patient Transport Types during Long Dwells: A Modeling Study

et al. 2016

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♦ Background: In recent years, results from clinical studies have changed the focus of peritoneal dialysis (PD) adequacy from small solute clearance to volume control, resulting in continued efforts to improve fluid and sodium removal in PD patients. We used a modified 3-pore model to theoretically predict fluid and solute removal using glucose-based and icodextrin solutions for a wide range of transport characteristics with automated PD (APD) and continuous ambulatory PD (CAPD) therapies. ♦ Methods: Simulations were performed for the day (APD: 15-hr, 2.27% glucose and 7.5% icodextrin; CAPD: 3x5-hr, 1.36% and 2.27% glucose) and night (APD: 9-hr, 1.36% glucose; CAPD: 9-hr, 2.27% glucose and 7.5% icodextrin) dialysis periods separately. During APD, the number of night exchanges (N) was varied from 3 to 7. Ultrafiltration (UF), sodium removal (NaR), total carbohydrate absorption (CHO), UF efficiency (UFE), and sodium removal efficiency (NaRE) were calculated. Typical patients in fast (i.e. high, H), average (high-average, HA; low-average, LA), and slow (low, L) transport groups with no residual kidney function were considered. ♦ Results: The effective dwell times varied between 1.0 and 14.7 hours depending on the number of exchanges. With glucose-based solutions, differences in UF and NaR between H and L transport patients ranged from 140 mL and 2 mmol (APD night, n = 7) to 778 mL and 56.4 mmol (CAPD day, 2.27%). With icodextrin, differences in UF and NaR ranged from 1 mL and 1.1 mmol (CAPD night) to 59 mL and 6.1 mmol (APD day). The use of icodextrin resulted in greater CHO than 2.27% glucose (APD: 27.1 -35.6 g more; CAPD: 17.1 -17.5 g more). The UFE and NaRE were greater for all patients with icodextrin than with glucose-based solution in both therapy modalities, except for slow transport patients in CAPD. ♦ Conclusion: This modeling study shows that the dependence of UF and NaR on patient transport type observed with glucose-based solutions can be minimized using icodextrin during the long dwells of APD and CAPD. While this approach simplifies the PD prescription by minimizing the dependencies of ultrafiltration and sodium removal on patient transport type when using icodextrin, it improves fluid and sodium removal efficiencies in fast and average transport patients without any added glucose exposure.

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Peritoneal Residual Volume Induces Variability of Ultrafiltration with Icodextrin

Cited by 8 publications

References 30 publications

Predicting the Peritoneal Absorption of Icodextrin in Rats and Humans Including the Effect of α–Amylase Activity in Dialysate

Predicting the Peritoneal Absorption of Icodextrin in Rats and Humans Including the Effect of α–Amylase Activity in Dialysate

Low-Polydispersity Glucose Polymers as Osmotic Agents for Peritoneal Dialysis

Icodextrin Simplifies Pd Therapy by Equalizing Uf and Sodium Removal among Patient Transport Types during Long Dwells: A Modeling Study

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