Drug Safety

, Volume 5, Issue 2, pp 94–108 | Cite as

Amphotericin B Nephrotoxicity

  • Ramzi Sabra
  • Robert A. Branch
Review Article Drug Experience


The frequency of fungal infections is increasing. Amphotericin B remains the antifungal drug of choice for most systemic infections, but a limiting factor for its use is the development of nephrotoxicity. Amphotericin B-induced nephrotoxicity is manifested as azotaemia, renal tubular acidosis, impaired renal concentrating ability and electrolyte abnormalities like hypokalaemia and sodium and magnesium wasting. All these abnormalities occur to varying degrees in almost all patients receiving the drug. Upon withdrawal of therapy renal function gradually returns to baseline, although in some instances permanent damage is sustained, especially when the cumulative dose exceeds 5g. Salt depletion enhances the development of nephrotoxicity. The mechanism of nephrotoxicity involves direct cell membrane actions to increase permeability, as well as indirect effects secondary to activation of intrarenal mechanisms (tubuloglomerular feedback) and/or release of mediators (thromboxane A2). The latter effects are presumably responsible for the observed acute decreases in renal blood flow and filtration rate, responses that are inhibited by several physiological and pharmacological interventions. Changes in intracellular calcium levels may also contribute to the observed effects.

In the clinical situation, and in long term models of nephrotoxicity in the rat, salt loading protects against deterioration in renal function; recommendations are made for the optimisation of amphotericin B therapy by salt loading. New preparations of the drug, such as liposomal amphotericin B, may also prove useful in minimising nephrotoxicity while maintaining antifungal activity, but further research is needed with both salt loading and liposomal amphotericin B to confirm or deny their protective effect on kidney function.


Amphotericin Renal Blood Flow Liposomal Amphotericin Renal Tubular Acidosis Ticarcillin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© ADIS Press Limited 1990

Authors and Affiliations

  • Ramzi Sabra
    • 1
  • Robert A. Branch
    • 1
  1. 1.Division of Clinical Pharmacology, Departments of Pharmacology and MedicineVanderbilt University School of MedicineNashvilleUSA

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