JAC Advance Access published online on June 27, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm220
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Proteinuria lowers the risk of amphotericin B-associated hypokalaemia
Division of Nephrology, Department of Medicine, Harlem Hospital Center, Columbia, University College of Physicians and Surgeons, 506 Lenox Avenue, Room 12101, New York, NY 10037, USA
Received 23 October 2006; returned 16 December 2006; revised 18 May 2007; accepted 28 May 2007
* Corresponding author. Tel: +1-212-939-1453; Fax: +1-212-939-3890; E-mail: sm2206{at}columbia.edu
Objectives: Amphotericin B-induced nephrotoxicity is frequent, severe and associated with an increased risk of death. Patients with underlying renal disease are considered to be at high risk for amphotericin B nephrotoxicity. Amphotericin B is a molecule that is highly protein bound over a wide range of protein and drug concentrations, including those seen in patients with 
3+ proteinuria. We hypothesized that amphotericin B treatment in patients with proteinuria will be associated with less hypokalaemia than patients with non-proteinuric renal disease.
Methods: Thirty-six subjects who received amphotericin B deoxycholate were studied retrospectively. Twenty-five patients with proteinuria <3 g/L and 11 with proteinuria 3 g/L were compared.
Results: Hypokalaemia (K+<3.5 mmol/L) developed in 47.2% (17/36) of our cohort of patients. There was a 64% (16/25) incidence of hypokalaemia in the group with <3 g/L of proteinuria in contrast to an incidence of 9.1% (1/11) in the other group.
Conclusions: In our study, heavy proteinuria appears to protect the tubular luminal membrane by decreasing the luminal concentration of free drug available to bind with the membrane. Our findings redefine the patient population deemed to be at risk of developing amphotericin B nephrotoxicity. This ensures the benefit of this important antifungal treatment option to patients with heavy proteinuria who might otherwise not be administered this drug due to the presence of pre-existing kidney disease.
Key Words: nephrotoxicity , tubular toxicity , protein binding , drug–protein interaction , antifungal therapy , electrolyte abnormalities
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