Amphotericin B, mercury chloride and peritoneal transport in rabbits

Background: The effect of glucose-induced ultrafiltration in peritoneal dia lysis is dependent on the presence and function of ultrasmall transendothel ial cell water channels. The mercury-sensitive aquaporin-1 was thought to r epresent these transcellular pores. Amphotericin B (ampho B) has been repor ted to increase ultrafiltration in both experimental and patient studies. T he objective of this study was to investigate the hypothesis that intraperi toneal ampho B increases and mercury chloride inhibits aquaporin-1-mediated water transport in a chronic peritoneal dialysis model in the rabbit. Mate rial and methods: Eighteen female New Zealand White rabbits were included f or peritoneal catheter implantation. Peritoneal transport parameters were d etermined in all rabbits by standard peritoneal permeability analysis (SPAR ) with 3.86% glucose-based dialysis solution during a one-hour dwell prior the intervention SPARs, as a control. Ampho B (0.06 mg/kg body weight) was added to the dialysate for 3 (n = 9) or 5 consecutive days (n = 5) before i nvestigation. Four rabbits were investigated after 3-day i.p. 0.6 mg/kg bod y weight ampho B. In 3 rabbits 0.06 mg/kg body weight liposomal ampho B was administered i.p. during 3 days before intervention SPAR. Fifteen rabbits were investigated during a one-hour dwell with 0.1 mM HgCl2 containing 3.86 % glucose-based dialysis solution, while they were anesthetized. Three of t hese underwent in vivo fixation ih glutaraldehyde prior to the HgCl2 SPAR t o prevent toxic effects of mercury on peritoneal tissues. Results: Intraper itoneal administration of ampho B did enhance the change in intraperitoneal volume during a one-hour dwell after 3-day i.p. treatment with the low dos e (p < 0.02), but it did not affect peritoneal solute permeability. This wa s likely mediated by transcellular water channels, but not by aquaporin-1. No beneficial effects on the ultrafiltration were found with prolonged trea tment or with the higher dose, Ultrafiltration decreased (8 ml/4 h to 1 ml/ 4 h, p < 0.03) after i.p. administration of IIgCl(2) with and without in vi vo fixation, accompanied by a significant decrease in aquaporin-mediated wa ter transport, estimated as the sieving of sodium (p < 0.001). Marked incre ases in the clearances of macromolecules were found after i.p. HgCl2 admini stration due to toxic effects: total protein clearance from 97 to 172 mul/m in, p < 0.005, and albumin clearance from 59 to 158 mul/min, p < 0.005. The se changes were less pronounced after in vivo fixation. Conclusion: Ampho B has likely no clinical relevance in treatment of ultrafiltration failure i n PD patients. Aquaporin-mediated water transport could be inhibited and co nsequently ultrafiltration was reduced by i.p. administration of mercury ch loride in our rabbit model.