Polycation as an alternative osmotic agent and phosphate binder in peritoneal dialysis.

We have previously shown that polyanions can be utilized to achieve balanced removal of sodium and water during peritoneal dialysis. The excessive binding of potassium, calcium, and magnesium to anionic polymers proves undesirable. The present study was designed to demonstrate the reversibility of cation binding by using a polycation (polyethylenimine) as the osmotic agent, thus favoring the removal of undesirable excess phosphate anions via peritoneal dialysis. Polyethylenimine shows a measurable affinity for phosphorus when present as dialysate in an in vitro system simulating peritoneal dialysis. The polycation also stimulates ultrafiltration across the rat peritoneum when present in dialysate. The polymer is toxic to the rat and light microscopy reveals gross morphological tissue alterations of the visceral mesothelium and associated organs. We have demonstrated that a polycation can give ultrafiltration with enhanced removal of phosphate. Although the polymer we chose as a prototype is toxic to the rat, other polycations should be studied.

Polyanions and glucose as osmotic agents in simulated peritoneal dialysis.

Peritoneal dialysis solutions contain glucose as an osmotic agent to obtain ultrafiltration. Due to rapid absorption, glucose does not sustain high ultrafiltration during long exchanges. Nonabsorbable polyanions might be effective as osmotic agents when suspended in electrolyte solution. Concentrations of freely diffusible ions should be in Gibbs-Donnan equilibrium with plasma electrolytes. The ideal proportion of diffusable to polymerbound cation concentrations is unknown. To obtain concentrations of free ions in equilibrium with plasma, it is assumed that the polymer solution dialyzed against a polyelectrolyte solution of the desired composition (with hydraulic pressure higher on the polymer side) will approach the same thermodynamic activity as the electrolyte solution. Subsequently, if transmembrane pressure is released, osmotic ultrafiltration will occur in proportion to the hydrostatic pressure applied during polymer solution preparation. Polyacrylate solution so prepared was compared with a commercial dextrose dialysis solution in an in vitro simulation of peritoneal dialysis. With dwell times up to 24 h, sustained ultrafiltration with polymer was observed, whereas, with dextrose, ultrafiltration ceased after 8 h. Concentrations of diffusible bivalent cations in polyacrylate were lower than intended due to avid polymer complexing; however, dextran sulfate solutions were developed to contain desired concentrations of diffusible electrolytes. The conclusion is that some polymer solutions might be useful in clinical settings when high sustained ultrafiltration is needed.

Insulin binding to plastic bags: a methodologic study.

A radiotracer method to assess insulin binding to commercially available plastic peritoneal dialysis solution containers was developed. A peritoneal dialysis bag (bag 2) was emptied and attached to another full bag (bag 1) of the same kind. In the syringe-to-bag method, bag 1 was symmetrically injected through the bag wall with four syringes containing dialysis solution and radioactive insulin, with or without regular insulin. The radioactivity in each syringe was measured with a gamma counter before injection, and all of the samples were counted afterwards directly in the syringes. Using a bag-to-bag transfer method, bag 1 was agitated, eight samples were taken from different parts through the wall, and then the contents were transferred to bag 2. Bag 2 was then agitated and eight samples were taken and counted. In the bag-pieces method, pieces of bag wall were cut and the radioactivity on the walls was measured to determine the amount of binding. The syringe-to-bag method gave negative results, severely underestimating the amount of insulin binding. The bag-to-bag transfer method yielded positive results in all instances. Increasing the amounts of regular insulin had no demonstrable impact on percent of binding. When the bag-to-bag method was compared with the bag-pieces method, it gave only slightly higher values; however, the bag-to-bag method was considered more reliable because the counting can be controlled more effectively. A 15-minute delay in sampling was not found to influence insulin binding. A reliable method of assessing insulin binding must be based on the following two principles: (1) The transfer of samples to intermediate containers should be avoided, and (2) radiotracer concentrations in the samples should be similar.

Nature of insulin binding to plastic bags.

The nature of insulin binding to plastic bags was evaluated to determine if it followed the physical laws of adsorption. To determine whether insulin is adsorbed on a liquid/air interface, the influence of foam in vials of radiolabeled insulin was evaluated. Using a bag-to-bag transfer method, the influence of regular insulin and detergent on radiotracer insulin binding was assessed. To evaluate the reversibility of the binding, bag pieces with bound radioactive insulin were washed with distilled water, detergent, and left to soak in detergent before measuring radioactivity. The radiolabeled insulin was adsorbed in the foam and then released into the bulk of the solution when the foam disappeared; hence, insulin can be entrapped in a liquid/air interface. The addition of regular insulin decreased the binding of the radiotracer insulin to the bag walls. The bound insulin could be removed by washing with water and detergent, but soaking in detergent did not remove a small residual quantity of the bound insulin, suggesting that minimal chemical binding or diffusion of the insulin into the plastic may occur. Insulin binding to plastic bags primarily follows the physical laws of adsorption.

Influence of temperature and time on insulin adsorption to plastic bags.

The influence of temperature and time on insulin adsorption to plastic peritoneal dialysis bags was evaluated. A dialysis bag (1.5% dextrose, 2 liters) was injected with 25-microCi insulin I 125 and gently mixed. This bag was then attached to another empty bag of the same type. Following a bag-to-bag transfer method, the amount of insulin adsorbed on the plastic bags was measured at 24 degrees C and 37 degrees C, and after a 12-hour warming period at 37 degrees C. Regular insulin was added to the system in 40-unit increments up to 280 units. Radioactivity in all of the samples was measured in a gamma counter. As the amount of regular insulin increased, the percentage of insulin adsorbed decreased at both temperatures. More insulin was bound at 37 degrees C than at 24 degrees C for all levels of insulin. Data calculated according to the Langmuir isotherm equation showed that the maximum possible values of adsorption to the system at 24 degrees C and 37 degrees C were 17.8 and 18.4 units, respectively. The affinity constants at 24 degrees C and 37 degrees C were 0.0039 and 0.0065, respectively. The influence of prolonged warming at 37 degrees C was minimal. At the usual dosage of insulin (below 40 units) prescribed to the majority of dialysis patients, less than 9% (3.5 units) is adsorbed onto the dialysis bags.

Enhancement of clearances by activated charcoal in an in vitro model of peritoneal dialysis.

The use of sorbents in dialysate to increase solute clearances in continuous ambulatory peritoneal dialysis (CAPD) was investigated. With in vitro simulations of CAPD, the kinetics of irreversible binding of creatinine to activated charcoal were assessed. Cellulose dialyzer fibers were submerged in two liters of dialysate for 3-8 hour exchanges. Perfusate was pumped single pass through the fibers. Commercial dialysates with 1.5% and 4.25% dextrose as an osmotic agent were controls. Experimental exchanges contained either large or small particles of activated charcoal. Unencapsulated and collodion encapsulated large particles were also studied. From the perfusate side, creatinine, clearance and mass transfer were determined; dialysate/perfusate ratios (D/P) of free creatinine concentrations were assessed. We found that incorporation of small unencapsulated particles of activated charcoal would double both clearance and mass transfer of creatinine. It also maintained D/P values less than 0.6 even up to 8 hours. Small particles absorbed more than 10 times more creatinine per gram than large particles. Significant differences between encapsulated and unencapsulated large particles were not found. In summary, activated charcoal might double creatinine removal per exchange in CAPD. Animal studies of collodion encapsulated small particles and other sorbent-enzyme systems in CAPD dialysate solutions seem warranted.

In vitro simulations of peritoneal dialysis. A technique for demonstrating limitations on solute clearances due to stagnant fluid films and poor mixing.

Stagnant fluid films in the peritoneal interstitium and peritoneal cavity may explain low clearances during peritoneal dialysis. Various peritoneal dialysis techniques may influence clearances by enhancing mixing. However, such techniques also may change fresh fluid replacement rates and/or after peritoneal membrane transport characteristics secondary to mechanically, osmotically, or chemically induced changes in the peritoneium and its vasculature. Various techniques were evaluated in an in vitro simulation of peritoneal dialysis where membrane transport characteristics would not change and the impact of better mixing alone could be assessed. Only very vigorous agitation of fluid appears to influence stagnant fluid film resistances under the conditions of these studies. In actual peritoneal dialysis, fluid film resistances are probably even less likely to be influenced by existing techniques.