A double-blinded, placebo-controlled clinical trial of N-acetyl cysteine for preventing amphotericin b nephrotoxicity


Authors:

1- Iman Karimzadeh, PharmD, PhD, Assistant Professor, Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran, Tel: +98 (713) 2424128, E-mail: karimzadehiman@yahoo.com 2- Hossein Khalili, PharmD, PhD, Full Professor, Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, Tel & Fax: +98 (21) 66954709, E-mail: khalilih@tums.ac.ir 3- Simin Dashti-Khavidaki, PharmD, PhD, Associated Professor, Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran, Tel & Fax: +98 (21) 66954709, E-mail: dashtis@tums.ac.ir 4- Mohammad Mahdi Sagheb, MD, Nephrologist, Associated Professor, Nephrology-Urology Research Center and Department of Internal Medicine, Shiraz University of Medical Sciences, Shiraz, Iran, Tel: +98 (711) 2351087, E-mail: saghebm@sums.ac.ir

Correspondence:

Iman Karimzadeh, PharmD, PhD, Assistant Professor, Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran, Tel: +98 (713) 2424128, E-mail: karimzadehiman@yahoo.com

Aim: To evaluate the effectiveness of oral n-acetyl cysteine co-treatment in preventing and/or attenuating amphotericin b-induced nephrotoxicity.

Methods: During a 24-month period from early August 2011 to early August 2013, patients planned to receive conventional amphotericin b for any indication for at least one week, were randomly allocated to receive either placebo or 600 mg oral n-acetyl cysteine twice daily during the treatment course of amphotericin b. Different aspects of amphotericin b nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, renal magnesium and potassium wasting were assessed. Serum as well as urinary level of cystatin C and urinary KIM-1 were determined at three time points within amphotericin b treatment course including days 0, 7, and 14.

Results: Within the study period, 103 patients were screened primarily. Of these, 54 subjects met the inclusion/exclusion criteria and were randomly allocated into two equal groups (27 versus 27 in placebo and n-acetyl cysteine groups, respectively). Finally, 40 individuals including 21 in n-acetyl cysteine and 19 in the placebo group completed the study. There were no statistically significant differences among studied demographic, clinical, and paraclinical variables in both groups. Among the study population, 23 (42.59%) patients developed amphotericin b nephrotoxicity during their treatment course. After adjusting our intervention separately for each probable associated factor along with potential nephroprotective measures against amphotericin b nephrotoxicity, n-acetyl cysteine co-treatment was significantly associated with mitigating amphotericin b nephrotoxicity (OR=0.286,95 % CI: 0.082-0.993; P=0.049). In contrast, incidence and time onset of hypokalemia, hypomagnesemia, renal potassium and magnesium wasting were comparable between two groups. No statistically significant difference regarding accuracy of measured biomarkers including serum creatinine, serum and urine cystatin C and urine KIM-1 at days 0 and 7 of treatment in predicting and detecting amphotericin b nephrotoxicity was identified. The changes in mean serum and urine cystatin C and urine KIM during amphotericin b treatment within and between treatment groups were not statistically significant.

Conclusion: The data of our clinical trial suggested that co-treatment with 600 mg oral n-acetyl cysteine twice daily during amphotericin b treatment course was significantly effective in preventing or ameliorating amphotericin b-induced decreases of glomerular filtration rate but not hypokalemia, hypomagnesemia, and renal potassium as well as magnesium wasting.