Amphotericin B, mercury chloride and peritoneal transport in rabbits.
BACKGROUND
The effect of glucose-induced ultrafiltration in peritoneal dialysis is dependent on the presence and function of ultrasmall transendothelial cell water channels. The mercury-sensitive aquaporin-1 was thought to represent these transcellular pores. Amphotericin B (ampho B) has been reported to increase ultrafiltration in both experimental and patient studies. The objective of this study was to investigate the hypothesis that intraperitoneal ampho B increases and mercury chloride inhibits aquaporin-1-mediated water transport in a chronic peritoneal dialysis model in the rabbit.


METHODS
Eighteen female New Zealand White rabbits were included for peritoneal catheter implantation. Peritoneal transport parameters were determined 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 investigation. Four rabbits were investigated after 3-day i.p. 0.6 mg/kg body 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 these underwent in vivo fixation with glutaraldehyde prior to the HgCl2 SPAR to prevent toxic effects of mercury on peritoneal tissues.


RESULTS
Intraperitoneal 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 dose (p < 0.02), but it did not affect peritoneal solute permeability. This was likely mediated by transcellular water channels, but not by aquaporin-1. No beneficial effects on the ultrafiltration were found with prolonged treatment or with the higher dose. Ultrafiltration decreased (8 ml/4 h to 1 ml/4 h, p < 0.03) after i.p. administration of HgCl2 with and without in vivo fixation, accompanied by a significant decrease in aquaporin-mediated water transport, estimated as the sieving of sodium (p < 0.001). Marked increases in the clearances of macromolecules were found after i.p. HgCl2 administration due to toxic effects: total protein clearance from 97 to 172 microl/min, p < 0.005, and albumin clearance from 59 to 158 microl/min, p < 0.005. These changes were less pronounced after in vivo fixation.


CONCLUSIONS
Ampho B has likely no clinical relevance in treatment of ultrafiltration failure in PD patients. Aquaporin-mediated water transport could be inhibited and consequently ultrafiltration was reduced by i.p. administration of mercury chloride in our rabbit model.
Zweers
M M
MM
Department of Nephrology, Academic Medical Center Amsterdam, The Netherlands. M.M.Zweers@AMC.UVA.NL
Douma
C E
CE
de Waart
D R
DR
Korevaar
J C
JC
Krediet
R T
RT
Struijk
D G
DG
D000666:Amphotericin B / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D020346:Aquaporins / Q000502:physiology; D001693:Biological Transport, Active; D015314:Dialysis Solutions; D005260:Female; D005947:Glucose / Q000378:metabolism; D008627:Mercuric Chloride / Q000494:pharmacology*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism*; D011817:Rabbits; D018709:Statistics, Nonparametric; D014867:Water / Q000378:metabolism*
D020346:Aquaporins; D015314:Dialysis Solutions; D014867:Water; D008627:Mercuric Chloride; D000666:Amphotericin B; D005947:Glucose