Amphotericin B nephrotoxicity
- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor of Medicine
- University of Rochester School of Medicine and Dentistry
Amphotericin B is used in the treatment of often life-threatening fungal infections. (See "Pharmacology of amphotericin B".) Impaired renal function is a relatively common complication of amphotericin B, as are other renal manifestations, including urinary potassium wasting and hypokalemia, urinary magnesium wasting and hypomagnesemia, metabolic acidosis due to type 1 (or distal) renal tubular acidosis, and polyuria due to nephrogenic diabetes insipidus [1-5].
An overview of amphotericin B nephrotoxicity is presented here. The management of hypokalemia, hypomagnesemia, distal renal tubular acidosis, and nephrogenic diabetes insipidus is discussed in detail elsewhere. (See "Clinical manifestations and treatment of hypokalemia in adults", section on 'Treatment' and "Evaluation and treatment of hypomagnesemia", section on 'Treatment' and "Treatment of distal (type 1) and proximal (type 2) renal tubular acidosis", section on 'Distal (type 1) renal tubular acidosis' and "Treatment of nephrogenic diabetes insipidus".)
ACUTE KIDNEY INJURY
Incidence with conventional amphotericin B — Conventional amphotericin B (ie, not the lipid formulations) causes renal vasoconstriction and can reduce the glomerular filtration rate (GFR) by more than half [1-4,6,7]. In the two largest reviews, a 50 percent or greater increase in serum creatinine was observed in 138 of 494 and 174 of 643 patients (28 and 27 percent), respectively [4,6].
The risk of amphotericin-induced renal injury is influenced by other factors:
●Concurrent therapy with other nephrotoxins, such as an aminoglycoside, cyclosporine, or foscarnet, increases the risk of acute kidney injury [4,6-8]. In one report, the incidence of a twofold or greater increase in serum creatinine was 15 percent in patients taking no or one concurrent nephrotoxic drug and 41 percent in those taking two or more concurrent nephrotoxic drugs .
- Branch RA. Prevention of amphotericin B-induced renal impairment. A review on the use of sodium supplementation. Arch Intern Med 1988; 148:2389.
- Sawaya BP, Briggs JP, Schnermann J. Amphotericin B nephrotoxicity: the adverse consequences of altered membrane properties. J Am Soc Nephrol 1995; 6:154.
- BUTLER WT, BENNETT JE, ALLING DW, et al. NEPHROTOXICITY OF AMPHOTERICIN B; EARLY AND LATE EFFECTS IN 81 PATIENTS. Ann Intern Med 1964; 61:175.
- Bates DW, Su L, Yu DT, et al. Correlates of acute renal failure in patients receiving parenteral amphotericin B. Kidney Int 2001; 60:1452.
- Barton CH, Pahl M, Vaziri ND, Cesario T. Renal magnesium wasting associated with amphotericin B therapy. Am J Med 1984; 77:471.
- Harbarth S, Pestotnik SL, Lloyd JF, et al. The epidemiology of nephrotoxicity associated with conventional amphotericin B therapy. Am J Med 2001; 111:528.
- Walsh TJ, Finberg RW, Arndt C, et al. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med 1999; 340:764.
- Fisher MA, Talbot GH, Maislin G, et al. Risk factors for Amphotericin B-associated nephrotoxicity. Am J Med 1989; 87:547.
- Heidemann HT, Gerkens JF, Spickard WA, et al. Amphotericin B nephrotoxicity in humans decreased by salt repletion. Am J Med 1983; 75:476.
- Zager RA, Bredl CR, Schimpf BA. Direct amphotericin B-mediated tubular toxicity: assessments of selected cytoprotective agents. Kidney Int 1992; 41:1588.
- Heyman SN, Stillman IE, Brezis M, et al. Chronic amphotericin nephropathy: morphometric, electron microscopic, and functional studies. J Am Soc Nephrol 1993; 4:69.
- Blantz RC, Pelayo JC. A functional role for the tubuloglomerular feedback mechanism. Kidney Int 1984; 25:739.
- Sawaya BP, Weihprecht H, Campbell WR, et al. Direct vasoconstriction as a possible cause for amphotericin B-induced nephrotoxicity in rats. J Clin Invest 1991; 87:2097.
- Tolins JP, Raij L. Chronic amphotericin B nephrotoxicity in the rat: protective effect of calcium channel blockade. J Am Soc Nephrol 1991; 2:98.
- Llanos A, Cieza J, Bernardo J, et al. Effect of salt supplementation on amphotericin B nephrotoxicity. Kidney Int 1991; 40:302.
- Dórea EL, Yu L, De Castro I, et al. Nephrotoxicity of amphotericin B is attenuated by solubilizing with lipid emulsion. J Am Soc Nephrol 1997; 8:1415.
- Veerareddy PR, Vobalaboina V. Lipid-based formulations of amphotericin B. Drugs Today (Barc) 2004; 40:133.
- Luke RG, Boyle JA. Renal effects of amphotericin B lipid complex. Am J Kidney Dis 1998; 31:780.
- Alexander BD, Wingard JR. Study of renal safety in amphotericin B lipid complex-treated patients. Clin Infect Dis 2005; 40 Suppl 6:S414.
- White MH, Anaissie EJ, Kusne S, et al. Amphotericin B colloidal dispersion vs. amphotericin B as therapy for invasive aspergillosis. Clin Infect Dis 1997; 24:635.
- Mistro S, Maciel Ide M, de Menezes RG, et al. Does lipid emulsion reduce amphotericin B nephrotoxicity? A systematic review and meta-analysis. Clin Infect Dis 2012; 54:1774.
- Messori A, Fadda V, Maratea D, et al. Nephrotoxicity of different formulations of amphotericin B: summarizing evidence by network meta-analysis. Clin Infect Dis 2013; 57:1783.
- Wingard JR, White MH, Anaissie E, et al. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis 2000; 31:1155.
- Bicanic T, Bottomley C, Loyse A, et al. Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis. Antimicrob Agents Chemother 2015; 59:7224.
- Douglas JB, Healy JK. Nephrotoxic effects of amphotericin B, including renal tubular acidosis. Am J Med 1969; 46:154.
- Gil FZ, Malnic G. Effect of amphotericin B on renal tubular acidification in the rat. Pflugers Arch 1989; 413:280.
- Batlle DC. Segmental characterization of defects in collecting tubule acidification. Kidney Int 1986; 30:546.
- Atsmon J, Dolev E. Drug-induced hypomagnesaemia : scope and management. Drug Saf 2005; 28:763.
- Wazny LD, Brophy DF. Amiloride for the prevention of amphotericin B-induced hypokalemia and hypomagnesemia. Ann Pharmacother 2000; 34:94.
- Hemstreet BA. Antimicrobial-associated renal tubular acidosis. Ann Pharmacother 2004; 38:1031.
- Zietse R, Zoutendijk R, Hoorn EJ. Fluid, electrolyte and acid-base disorders associated with antibiotic therapy. Nat Rev Nephrol 2009; 5:193.
- Canada TW, Weavind LM, Augustin KM. Possible liposomal amphotericin B-induced nephrogenic diabetes insipidus. Ann Pharmacother 2003; 37:70.
- Sacks P, Fellner SK. Recurrent reversible acute renal failure from amphotericin. Arch Intern Med 1987; 147:593.