A double-blinded, placebo-controlled, multicenter clinical trial of N-acetylcysteine for preventing amphotericin B-induced nephrotoxicity

Expert Opin Drug Metab Toxicol. 2015;11(9):1345-55. doi: 10.1517/17425255.2015.1042363. Epub 2015 Jun 11.

Abstract

Objective: To evaluate the effectiveness of oral N-acetylcysteine (NAC) co-treatment in preventing amphotericin B (AmB)-induced nephrotoxicity (AIN), including creatinine clearance and biomarkers of renal function (cystatin C [Cys C] and kidney injury molecule-1 [KIM-1]).

Methods: Either placebo or 600 mg oral NAC was given twice daily during the treatment course of AmB. Renal function test, serum as well as urinary level of Cys C and urinary KIM-1 were determined.

Results: Among the study population (n = 54), 23 (42.59%) patients developed AmB nephrotoxicity during their treatment course. NAC co-treatment was significantly associated with mitigating AmB nephrotoxicity (OR = 0.286, 95% CI: 0.082 - 0.993; p = 0.049). No statistically significant difference regarding accuracy of measured biomarkers including serum creatinine, serum and urine Cys C and urine KIM-1 at days 0 and 7 of treatment in predicting and detecting AmB nephrotoxicity was identified. The changes in mean serum and urine Cys C and urine KIM during AmB treatment within and between treatment groups were not statistically significant.

Conclusions: Co-treatment with 600 mg oral NAC twice a day during AmB treatment, after adjusting for multiple variables, was associated with prevention of AIN. However, significantly higher adverse reactions developed in the patients who were treated with NAC.

Keywords: N-acetylcysteine; amphotericin B; nephrotoxicity; prevention.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acetylcysteine / administration & dosage
  • Acetylcysteine / therapeutic use*
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amphotericin B / adverse effects*
  • Amphotericin B / therapeutic use
  • Antifungal Agents / adverse effects*
  • Antifungal Agents / therapeutic use
  • Cystatin C / urine
  • Double-Blind Method
  • Female
  • Hepatitis A Virus Cellular Receptor 1
  • Humans
  • Kidney Diseases / chemically induced
  • Kidney Diseases / prevention & control*
  • Kidney Function Tests
  • Male
  • Membrane Glycoproteins / urine
  • Middle Aged
  • Receptors, Virus
  • Young Adult

Substances

  • Antifungal Agents
  • Cystatin C
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Membrane Glycoproteins
  • Receptors, Virus
  • Amphotericin B
  • Acetylcysteine