Eva Chakrabarti

The Role of the Capillary Wall in Restricting Diffusion of Macromolecules

In 5 nephrectomized rabbits the peritoneal clearance of neutral dextrans from plasma to dialysate decreased from 7.8 to 3.3 microliters/kg/min as molecular mass increased from 17,000 to 43,000 daltons, and was relatively constant at 2.8 microliters/kg/min from 49,000 to 97,000 daltons in accord with prior studies. The clearance from dialysate to plasma was measured by determining the distribution volume, which averaged 72 ml/kg, and the plasma concentration 5 h after intraperitoneal instillation. Inward clearances ranged from 11.4 to 19.9 microliter/kg/min, did not correlate well with solute size and were significantly higher than outward clearances. The data suggest that while the capillary wall is the major barrier to macromolecule transfer, absorption can bypass vascular capillaries and occur via the lymphatics. It is suggested that lymphatic flow rate from the peritoneum exceeds 16 microliter/kg/min.

Amphotericin selectively increases peritoneal ultrafiltration.

Because amphotericin B is known to affect transport rates across biologic membranes, the effects of this agent on transport parameters in an animal model of peritoneal dialysis were investigated. When amphotericin B in doses ranging from 0.5 to 25 mg/kg was instilled intraperitoneally with commercial dialysis solution, diffusive clearances of phosphate and urea did not differ from control values measured in the same animals, and only a modest increase in potassium clearance was detected. Ultrafiltration due to the osmotic gradient induced by the dextrose content of the dialysis solution increased significantly to 0.31 mL/kg/min with amphotericin B, compared with control values of 0.18 mL/kg/min. The drug did not affect dextrose transport and the osmotic gradient did not differ in the two groups. Hence, the ultrafiltration coefficient was higher with amphotericin B (14 microL/kg/min/mosm), than during control dialyses (6 microL/kg/min/mosm). Increased water flux was detected at the lowest dose and there was no dose relationship over the range studied. Amphotericin B may be the type of agent that will be clinically useful in patients with reduced peritoneal ultrafiltration capacity, and safer analogues should be explored.

Ultrafiltration by hyperosmotic peritoneal dialysis fluid excludes intracellular solutes.

During peritoneal dialysis, progressive increments in the osmotic gradient increase ultrafiltration rate. Solute transport by convective flux is thereby raised but there is no preferential increase in potassium clearance. The data imply that ultrafiltrate derives from extracellular fluid alone. Mesothelial cells appear to resist solute and water flux in response to an immediately adjacent osmotic gradient.

Contrasting effects of amphotericin B and the solvent sodium desoxycholate on peritoneal transport.

To distinguish amphotericin B effects on peritoneal transport from those of the solvent, sodium desoxycholate, dialyses in intact rabbits with either substance added intraperitoneally were compared to controls. Powered amphotericin B added to instilled dialysis fluid increased peritoneal ultrafiltration from 0.31 to 0.44 ml/kg/min (p less than 0.02), but did not affect mass transport (e.g. urea clearance changed from 0.86 to 1.04 ml/kg/min). In contrast, 10 mg of desoxycholate induced peritoneal irritation and raised clearances of urea (0.76-1.34 ml/kg/min), potassium, phosphate and dextrose, but did not affect ultrafiltration. Intraperitoneally, 1 mg/kg of desoxycholate changed clearances inconsistently, but lowered the ultrafiltration rate from 0.33 to 0.21 ml/kg/min. The dialysate-plasma dextrose gradient dissipated faster with 10 mg/kg of desoxycholate. Amphotericin B tended to raise ultrafiltration per osmotic gradient and mass transport of sodium. Selective increase in fluid flux results from amphotericin B, not its solvent.

Prolonged intraperitoneal dwell decreases ultrafiltration coefficient in rabbits.

In rabbits undergoing peritoneal dialysis, hypertonic (6% dextrose) dialysis solution increased the net ultrafiltration rate (UF) from 233 to 462 microL/kg/min, which was not proportional to the increment in the osmotic gradient, so the ultrafiltration coefficient decreased. As intraperitoneal dwell of hypertonic dialysate was prolonged, the gross and net UFs and ultrafiltration coefficients decreased, and the UF per dextrose absorption declined. The decrement in UF was multifactorial, including a component of fluid and solute stagnation, increasing the distance over which osmotic forces must exert their effects. Excessively hypertonic dialysis fluid should be used only briefly to achieve ultrafiltration efficiently and to avoid the high dextrose loading.