Prevention of Amphotericin B--Induced Renal Impairment: A Review on the Use of Sodium Supplementation

doi:10.1001/archinte.1988.00380110049010

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Vol. 148 No. 11, November 1988

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Prevention of Amphotericin B—Induced Renal Impairment

A Review on the Use of Sodium Supplementation

Robert A. Branch, MD

Arch Intern Med. 1988;148(11):2389-2394.

Abstract

• Amphotericin B is the treatment of choice for most deepseatedmycoses; however, doses may have to be limited because of concernover adverse effects such as nephrotoxicity. Evolving evidencesuggests that the extent of amphotericin B—induced renalimpairment may be modified via alteration of a normal physiologicfeedback response that further contributes to changes due todirect nephrotoxicity. As such, renal impairment has a substantialtheoretically preventable and reversible element. In animalsexposed to amphotericin B, sodium loading interferes with thisresponse. Mounting clinical evidence also supports the usefulnessof sodium supplementation to prevent as well as to reverse amphotericinB—induced nephrotoxicity. At this time, the use of sodiumsupplementation (eg, intravenous saline and/or ticarcillin disodium,which contains 5.2 mEq of sodium per gram of drug) along withavoiding dehydration appears to be a safe and effective meansof reducing the risk of nephrotoxicity associated with amphotericinB administration; however, it is not known whether renal changescan be entirely prevented. These preliminary observations meritconfirmation in a prospective, randomized clinical trial.

(Arch Intern Med 1988;148:2389-2394)

The incidence of mycotic disease is increasing. A recent surveyindicates that fungal organisms are isolated in from 1% to 12%of hospitalized patients, currently accounting for approximately5% of all cases of primary septicemia.¹ The reason for thisescalation in mycotic disease is the increased number of patientsoccupying hospital beds with risk factors for fungal infections.The major risk factor is impaired host defense mechanisms dueto underlying disease (eg, acquired immunodeficiency syndrome)or therapeutic maneuvers (eg, cancer chemotherapy, radiotherapy,iatrogenic immunosuppression for organ transplantation).

Despite the availability of newer antifungal agents, amphotericinB (Fungizone) remains the broad-spectrum antifungal antibioticof choice for the treatment of deepseated mycotic infections.Unfortunately, this drug causes a variety of adverse effects,including fever, chills, nausea,

Author Affiliations

From the Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn.

Footnotes

Accepted for publication May 31, 1988.

Reprint requests to Department of Pharmacology, Vanderbilt UniversitySchool of Medicine, Nashville, TN 37232 (Dr Branch).

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