Amphotericin B–related nephrotoxicity

Be aware that liposomal amphotericin B is associated with less renal toxicity than regular amphotericin but can still cause renal injury
Abdelwahab Ward, BS Pharm, PharmD

Amphotericin B is a polyene antifungal agent that acts by binding directly to ergosterol on the fungal cell membrane, resulting in disruption of membrane integrity and cell death. Amphotericin B has activity against a very wide range of clinically important yeasts and molds. Resistance to amphotericin B is rare.

     Amphotericin B has been the gold standard for the treatment of invasive fungal diseases for many years. Despite the more recent advent of newer antifungal agents with broad spectrums of activity (e.g., caspofungin and voriconazole), amphotericin B remains the standard treatment for many severe infections. Amphotericin B is often associated with numerous side effects including nephrotoxicity and an infusion-related phenomenon marked by hypotension, fever, chills, and rigors.

In an effort to alleviate these side effects, three different lipid-based products have been developed: liposomal amphotericin B (L-AMB) ― usual dose: (Ambisome) 3-5 mg/kg/day, amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD). It is important to note that these products should not be considered interchangeable, as each has different pharmacokinetic and physiochemical characteristics.

AMPHOTERICIN B–RELATED NEPHROTOXICITY

Occurs presumably as a result of its vasoconstrictive effects, as well as direct effects on the epithelial cell membranes and tubular dysfunction. Other renal toxicities associated with amphotericin B include potassium- and magnesium-wasting syndromes as well as renal tubular acidosis. As a result, a reversible decline in glomerular filtration rate (GFR) and a rise in serum creatinine up to as high as 2.5 mg/dL is not uncommon during a course of therapy. However, the resultant reduction in renal blood flow and GFR can also precipitate necrosis and acute renal failure (ARF) in some patients. Patients at greatest risk for developing ARF are the critically ill and patients receiving concomitant nephrotoxins (e.g., cyclosporine, aminoglycosides).

Numerous studies consistently suggest that lipid-based amphotericin products are associated with at least 50% less renal toxicity as compared with conventional amphotericin B. However, it is still important to note that nephrotoxicity and renal failure can still develop with the lipid-based products; therefore, close monitoring of urine output, electrolytes, blood urea nitrogen, and serum creatinine is warranted in all patients. Intravascular volume expansion with isotonic crystalloid solutions is indicated in all patients receiving amphotericin B products, as it may ameliorate the decline in GFR. A 500-mL bolus of 0.9% sodium chloride solution prior to each dose is recommended, provided the clinical situation permits. In many cases, aggressive electrolyte replacement and correction of acid-base disorders may be warranted.

REFERENCES

Abdelwahab Ward, BS Pharm, PharmD