How is nephrotoxic acute tubular necrosis (ATN) prevented?

Updated: Mar 15, 2021
  • Author: Sangeeta Mutnuri, MBBS; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

Strategies for prevention of nephrotoxic ATN vary with different nephrotoxins.

With aminoglycosides, studies have demonstrated that once-daily dosing decreases the incidence of nephrotoxicity. In one study, 24% of patients receiving 3 daily doses of gentamicin developed clinical nephrotoxicity, compared with only 5% of patients receiving 1 daily dose. [31] However, other studies comparing a single daily dose with multiple daily doses have failed to find a difference in the incidence of nephrotoxicity. Therapeutic efficacy is not diminished by single daily dosing.

With amphotericin B, efforts should be made to minimize the use of the drug and ensure that extracellular fluid volume is adequate. By saline loading, maintenance of a high urine flow rate has been shown to be helpful. Likewise, various lipid formulations of amphotericin B have been developed, namely, amphotericin B colloid dispersion (ABCD), amphotericin B complex (ABLC), and liposomal amphotericin B; these lipid formulations are believed to be intrinsically less nephrotoxic.

Whereas amphotericin B is suspended in bile salt deoxycholate, which has a detergent effect on cell membranes, the lipid formulations do not contain deoxycholate. The lipid formulations also bind more avidly to fungal cell wall ergosterol as opposed to the cholesterol in human cell membranes. Liposomal amphotericin B is preferred in patients with renal insufficiency or evidence of renal tubular dysfunction.

With cyclosporine and tacrolimus (calcineurin inhibitors), regular monitoring of blood levels can help maintain therapeutic levels and prevent nephrotoxicity. Usually, renal insufficiency is easily reversed by a reduction of the dosage. On the other hand, persistent injury can lead to interstitial fibrosis.

With cisplatin, the key to preventing renal injury is volume loading with saline. Some investigators advocate the use of amifostine, a thiol donor that serves as an antioxidant. Others prefer using carboplatin, a less nephrotoxic alternative.


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