Nephrotoxicity of amphotericin B is attenuated by solubilizing with lipid emulsion

Egidio Lima Dórea, Luis Yu, Isac De Castro, Silvia Campos-Bilderback, Maria Ori, Elisabeth Maria Heins Vaccari, Carlos Da Silva Lacaz, Antonio Carlos Seguro

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Nephrotoxicity is the major adverse effect of conventional amphotericin B (AMB/D), often limiting administration of full dosage. The new liposomal amphotericin B seems to be less toxic. In this study, it is proposed that solubilizing the standard AMB/D preparation with 10% lipid emulsion will attenuate nephrotoxicity. Rats were injected with either AMB/D (Fungizone), AMB, AMB/D plus lipid emulsion (AMB/D/LE), or sodium deoxycholate (D). Renal function studies were performed on day 5. To assess a direct tubular toxic effect, isolated rat proximal tubule suspensions and inner medullary collecting duct cells in culture were exposed to AMB/D, AMB, AMB/D/LE, liposomal amphotericin B, and D for 60 min in normoxia. Lactate dehydrogenase (LDH) release was assessed as an index of cell injury. Creatinine clearance (ml/min per 100 g) averaged 0.79 ± 0.04 in control rats, 0.29 ± 0.09 in AMB rats (P < 0.001 versus control), 0.38 ± 0.04 in AMB/D rats, 0.46 ± 0.05 in D rats, and 0.78 ± 0.03 in AMB/LE rats. Renal blood flow (ml/min per 100 g) was 3.45 ± 0.31 in control, 1.29 ± 0.28 in AMB, 1.42 ± 0.23 in AMB/D, 3.03 ± 0.39 in D, and 2.71 ± 0.21 in AMB/D/LE rats. The fractional excretion of potassium (%) was 27.3 ± 1.18 in control rats, 61.6 ± 7.00 in AMB/D rats, 58.4 ± 15.32 in AMB rats, and 37.9 ± 2.06 in AMB/D/LE rats. LDH release (%) in proximal tubules incubated with AMB/D and D was 43.6 ± 3.39 and 58.6 ± 4.20, respectively. Addition of lipid emulsion decreased LDH release: 21.6 ± 1.22 for AMB/D/LE and 26.4 ± 3.03 for deoxycholate plus lipid emulsion. AMB did not demonstrate any toxic effect in proximal tubule suspensions. D was not toxic to inner medullary collecting duct cells at 0.16 mg/ml, whereas D at a higher dose and AMB induced a significant LDH release. Addition of lipid emulsion did not affect the antifungal activity as assessed by the Etest method. In conclusion, an alternative way of administering standard AMB with reduced nephrotoxicity is proposed.

Original languageEnglish (US)
Pages (from-to)1415-1422
Number of pages8
JournalJournal of the American Society of Nephrology
Volume8
Issue number9
StatePublished - Sep 1997
Externally publishedYes

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Amphotericin B
Emulsions
Lipids
Poisons
L-Lactate Dehydrogenase
Deoxycholic Acid
Suspensions
Disk Diffusion Antimicrobial Tests
Renal Circulation
Creatinine
Potassium
Cell Culture Techniques
Kidney

ASJC Scopus subject areas

  • Nephrology

Cite this

Dórea, E. L., Yu, L., De Castro, I., Campos-Bilderback, S., Ori, M., Vaccari, E. M. H., ... Seguro, A. C. (1997). Nephrotoxicity of amphotericin B is attenuated by solubilizing with lipid emulsion. Journal of the American Society of Nephrology, 8(9), 1415-1422.

Nephrotoxicity of amphotericin B is attenuated by solubilizing with lipid emulsion. / Dórea, Egidio Lima; Yu, Luis; De Castro, Isac; Campos-Bilderback, Silvia; Ori, Maria; Vaccari, Elisabeth Maria Heins; Da Silva Lacaz, Carlos; Seguro, Antonio Carlos.

In: Journal of the American Society of Nephrology, Vol. 8, No. 9, 09.1997, p. 1415-1422.

Research output: Contribution to journalArticle

Dórea, EL, Yu, L, De Castro, I, Campos-Bilderback, S, Ori, M, Vaccari, EMH, Da Silva Lacaz, C & Seguro, AC 1997, 'Nephrotoxicity of amphotericin B is attenuated by solubilizing with lipid emulsion', Journal of the American Society of Nephrology, vol. 8, no. 9, pp. 1415-1422.
Dórea, Egidio Lima ; Yu, Luis ; De Castro, Isac ; Campos-Bilderback, Silvia ; Ori, Maria ; Vaccari, Elisabeth Maria Heins ; Da Silva Lacaz, Carlos ; Seguro, Antonio Carlos. / Nephrotoxicity of amphotericin B is attenuated by solubilizing with lipid emulsion. In: Journal of the American Society of Nephrology. 1997 ; Vol. 8, No. 9. pp. 1415-1422.
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abstract = "Nephrotoxicity is the major adverse effect of conventional amphotericin B (AMB/D), often limiting administration of full dosage. The new liposomal amphotericin B seems to be less toxic. In this study, it is proposed that solubilizing the standard AMB/D preparation with 10{\%} lipid emulsion will attenuate nephrotoxicity. Rats were injected with either AMB/D (Fungizone), AMB, AMB/D plus lipid emulsion (AMB/D/LE), or sodium deoxycholate (D). Renal function studies were performed on day 5. To assess a direct tubular toxic effect, isolated rat proximal tubule suspensions and inner medullary collecting duct cells in culture were exposed to AMB/D, AMB, AMB/D/LE, liposomal amphotericin B, and D for 60 min in normoxia. Lactate dehydrogenase (LDH) release was assessed as an index of cell injury. Creatinine clearance (ml/min per 100 g) averaged 0.79 ± 0.04 in control rats, 0.29 ± 0.09 in AMB rats (P < 0.001 versus control), 0.38 ± 0.04 in AMB/D rats, 0.46 ± 0.05 in D rats, and 0.78 ± 0.03 in AMB/LE rats. Renal blood flow (ml/min per 100 g) was 3.45 ± 0.31 in control, 1.29 ± 0.28 in AMB, 1.42 ± 0.23 in AMB/D, 3.03 ± 0.39 in D, and 2.71 ± 0.21 in AMB/D/LE rats. The fractional excretion of potassium ({\%}) was 27.3 ± 1.18 in control rats, 61.6 ± 7.00 in AMB/D rats, 58.4 ± 15.32 in AMB rats, and 37.9 ± 2.06 in AMB/D/LE rats. LDH release ({\%}) in proximal tubules incubated with AMB/D and D was 43.6 ± 3.39 and 58.6 ± 4.20, respectively. Addition of lipid emulsion decreased LDH release: 21.6 ± 1.22 for AMB/D/LE and 26.4 ± 3.03 for deoxycholate plus lipid emulsion. AMB did not demonstrate any toxic effect in proximal tubule suspensions. D was not toxic to inner medullary collecting duct cells at 0.16 mg/ml, whereas D at a higher dose and AMB induced a significant LDH release. Addition of lipid emulsion did not affect the antifungal activity as assessed by the Etest method. In conclusion, an alternative way of administering standard AMB with reduced nephrotoxicity is proposed.",
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AU - Dórea, Egidio Lima

AU - Yu, Luis

AU - De Castro, Isac

AU - Campos-Bilderback, Silvia

AU - Ori, Maria

AU - Vaccari, Elisabeth Maria Heins

AU - Da Silva Lacaz, Carlos

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N2 - Nephrotoxicity is the major adverse effect of conventional amphotericin B (AMB/D), often limiting administration of full dosage. The new liposomal amphotericin B seems to be less toxic. In this study, it is proposed that solubilizing the standard AMB/D preparation with 10% lipid emulsion will attenuate nephrotoxicity. Rats were injected with either AMB/D (Fungizone), AMB, AMB/D plus lipid emulsion (AMB/D/LE), or sodium deoxycholate (D). Renal function studies were performed on day 5. To assess a direct tubular toxic effect, isolated rat proximal tubule suspensions and inner medullary collecting duct cells in culture were exposed to AMB/D, AMB, AMB/D/LE, liposomal amphotericin B, and D for 60 min in normoxia. Lactate dehydrogenase (LDH) release was assessed as an index of cell injury. Creatinine clearance (ml/min per 100 g) averaged 0.79 ± 0.04 in control rats, 0.29 ± 0.09 in AMB rats (P < 0.001 versus control), 0.38 ± 0.04 in AMB/D rats, 0.46 ± 0.05 in D rats, and 0.78 ± 0.03 in AMB/LE rats. Renal blood flow (ml/min per 100 g) was 3.45 ± 0.31 in control, 1.29 ± 0.28 in AMB, 1.42 ± 0.23 in AMB/D, 3.03 ± 0.39 in D, and 2.71 ± 0.21 in AMB/D/LE rats. The fractional excretion of potassium (%) was 27.3 ± 1.18 in control rats, 61.6 ± 7.00 in AMB/D rats, 58.4 ± 15.32 in AMB rats, and 37.9 ± 2.06 in AMB/D/LE rats. LDH release (%) in proximal tubules incubated with AMB/D and D was 43.6 ± 3.39 and 58.6 ± 4.20, respectively. Addition of lipid emulsion decreased LDH release: 21.6 ± 1.22 for AMB/D/LE and 26.4 ± 3.03 for deoxycholate plus lipid emulsion. AMB did not demonstrate any toxic effect in proximal tubule suspensions. D was not toxic to inner medullary collecting duct cells at 0.16 mg/ml, whereas D at a higher dose and AMB induced a significant LDH release. Addition of lipid emulsion did not affect the antifungal activity as assessed by the Etest method. In conclusion, an alternative way of administering standard AMB with reduced nephrotoxicity is proposed.

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