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Defect in urinary acidification induced in vitro by amphotericin B
Amphotericin B impairs urinary acidification by increasing bladder membrane permeability, leading to hydrogen ion back-diffusion. This study reveals the mechanism behind amphotericin B
Area of Science:
- Nephrology
- Urology
- Physiology
Background:
- Amphotericin B is an antifungal agent known to cause renal toxicity.
- The precise mechanism of amphotericin B-induced urinary acidification defects remains incompletely understood.
Purpose of the Study:
- To investigate the effect of amphotericin B on hydrogen ion secretion in the isolated turtle bladder.
- To elucidate the role of passive permeability changes in amphotericin B-induced acidification defects.
Main Methods:
- Induction of experimental urinary acidification defect using amphotericin B in isolated turtle bladders.
- Measurement of net hydrogen ion secretion under short-circuited conditions with controlled electrochemical forces.
- Assessment of ion permeability changes (K+, Na+, Cl-) induced by amphotericin B.
Main Results:
- Amphotericin B minimally affected hydrogen ion secretion when passive forces were minimized.
- Hydrogen ion secretion against a gradient was significantly reduced and abolished at higher gradients (>2 pH units).
- Amphotericin B markedly increased luminal membrane permeability to potassium and moderately to sodium and chloride.
Conclusions:
- Impaired acidification is primarily due to increased passive permeability and hydrogen ion back-diffusion, not active transport failure.
- The observed in vitro defect mechanism may explain renal tubular defects in patients treated with amphotericin B.
- This study highlights the importance of membrane permeability in regulating urinary acidification.
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