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Amphotericin B does not increase peritoneal fluid removal
T Wang1, O Heimbürger, H H Cheng
1Division of Baxter Novum, Huddinge University Hospital, Karolinska Institute, Sweden.
Abstract:
Intraperitoneal use of amphotericin B (AmB) has been reported to increase ultrafiltration during short peritoneal dwell in rabbits. In this study, we investigated the effect of AmB on peritoneal fluid kinetics in rats. A 4 hour dwell using 25 mL of 2.27% glucose dialysis solution without AmB (control, n = 6), with 1 mg/kg (L-AmB, n = 6) or with 10 mg/kg AmB (H-AmB, n = 6), and with frequent dialysate and blood sampling was done in Sprague-Dawley rats. 131I-albumin was added to the solution as an intraperitoneal (i.p.) volume marker. There was no difference in the drainage volumes measured at 4 hours of the dwell (26.2 +/- 1.1 mL, 26.0 +/- 1.5 mL, and 26.0 +/- 1.1 mL for the control, L-AmB, and H-AmB groups, respectively.) However, the i.p. volumes were higher at 60 minutes, 90 minutes, and 120 minutes of the dwell in the H-AmB group as compared to the other two groups (1 to 1.5 mL higher, all P < 0.05). There were no differences in the peritoneal fluid absorption rate (KE) and the lymphatic flow rate (KEB) between the three groups. The D/D0 for glucose and dialysis-over-plasma concentration ratio (D/P) values for urea, sodium, and total protein, as well as the diffusive mass transport coefficient (KBD) values for these solutes did not differ among the three groups. However, the D/P as well as the KBD values for potassium were significantly higher in the H-AmB and L-AmB groups as compared to the control group, resulting in significantly higher potassium clearances among the two AmB groups as compared to the control group. Our results suggest that i.p. use of AmB did not increase peritoneal fluid removal after 4 hours of dwell in rats. Although the basic membrane permeability may not be altered by AmB, the higher D/P and KBD values as well as the higher clearances for potassium in the AmB groups may suggest a local release of potassium due to the cytotoxic effect of AmB. The contribution of water release from local cells to the increase in i.p. volume in the H-AmB group cannot be ruled out.
Insights
Intraperitoneal amphotericin B (AmB) did not increase peritoneal fluid removal in rats after a 4-hour dwell. However, AmB administration led to higher potassium levels, suggesting a potential cytotoxic effect.
Area of Science:
- Nephrology
- Pharmacology
- Peritoneal Dialysis
Background:
- Intraperitoneal amphotericin B (AmB) has been linked to increased ultrafiltration in rabbits.
- The effect of AmB on peritoneal fluid kinetics in rats remains to be fully elucidated.
Purpose of the Study:
- To investigate the impact of intraperitoneal amphotericin B on peritoneal fluid kinetics in a rat model.
- To determine if AmB influences fluid absorption, solute transport, and potassium levels during peritoneal dialysis.
Main Methods:
- Rats underwent a 4-hour peritoneal dwell with dialysis solution containing either no AmB (control), low-dose AmB (L-AmB), or high-dose AmB (H-AmB).
- Intraperitoneal volume was tracked using 131I-albumin, with frequent sampling of dialysate and blood.
- Solute transport (glucose, urea, sodium, potassium, total protein) was assessed by measuring dialysis-to-plasma concentration ratios (D/P) and diffusive mass transport coefficients (KBD).
Main Results:
- No significant differences in total fluid drainage volume were observed between groups after 4 hours.
- Higher intraperitoneal volumes were noted in the H-AmB group at earlier time points (60-120 minutes).
- Potassium D/P and KBD values, along with potassium clearances, were significantly higher in both AmB groups compared to the control.
Conclusions:
- Intraperitoneal AmB does not enhance peritoneal fluid removal after a 4-hour dwell in rats.
- While membrane permeability appears unaffected, elevated potassium levels suggest a localized cytotoxic effect of AmB.
- The potential contribution of cellular water release to increased intraperitoneal volume in the H-AmB group cannot be excluded.