A double-blind, randomized, controlled trial on N-acetylcysteine for the prevention of acute kidney injury in patients undergoing allogeneic hematopoietic stem cell transplantation.
Acute kidney injury (AKI) is one of the complications of hematopoietic stem cell transplantation and is associated with increased mortality. N-acetylcysteine (NAC) is a thiol compound with antioxidant and vasodilatory properties that has been investigated for the prevention of AKI in several clinical settings. In the present study, we evaluated the effects of intravenous NAC on the prevention of AKI in allogeneic hematopoietic stem cell transplantation patients. A double-blind randomized placebo-controlled trial was conducted, and 80 patients were recruited to receive 100 mg/kg/day NAC or placebo as intermittent intravenous infusion from day -6 to day +15. AKI was determined on the basis of the Risk-Injury-Failure-Loss-End-stage renal disease and AKI Network criteria as the primary outcome. We assessed urine neutrophil gelatinase-associated lipocalin (uNGAL) on days -6, -3, +3, +9 and +15 as the secondary outcome. Moreover, transplant-related outcomes and NAC adverse reactions were evaluated during the study period. Statistical analysis was performed using appropriate parametric and non-parametric methods including Kaplan-Meier for AKI and generalized estimating equation for uNGAL. At the end of the trial, data from 72 patients were analysed (NAC: 33 patients and placebo: 39 patients). Participants of each group were not different considering baseline characteristics. AKI was observed in 18% of NAC recipients and 15% of placebo group patients, and the occurrence pattern was not significantly different (p = 0.73). Moreover, no significant difference was observed between groups for uNGAL measures (p = 0.10). Transplant-related outcomes were similar for both groups, and all patients had successful engraftment. Three patients did not tolerate NAC because of abdominal pain, shortness of breath and rash with pruritus and were dropped from the intervention group before transplantation. However, the frequency of adverse reactions was not significantly different between groups. In conclusion, our findings could not show any clinical benefits from high-dose NAC particularly for AKI prevention in allogeneic hematopoietic stem cell transplantation patients.
Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Sara
S
Ataei
Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran.
Molouk
M
Hadjibabaie
Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Amirhossein
A
Moslehi
Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran.
Maryam
M
Taghizadeh-Ghehi
Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran.
Asieh
A
Ashouri
Department of Pharmaceutical Care, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Elham
E
Amini
Clinical Pharmacy Department, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.|Research Center for Rational Use of Drugs, Tehran University of Medical Sciences, Tehran, Iran.
Kheirollah
K
Gholami
Department of Pharmacy Practice, School of Pharmacy, Loma Linda University, Loma Linda, CA, USA.
Alireza
A
Hayatshahi
Hematology-Oncology and Stem Cell Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad
M
Vaezi
Hematology-Oncology and Stem Cell Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Ardeshir
A
Ghavamzadeh
D015746:Abdominal Pain / Q000139:chemically induced; D000111:Acetylcysteine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D058186:Acute Kidney Injury / Q000209:etiology / Q000517:prevention & control*; D000328:Adult; D064591:Allografts; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D003875:Drug Eruptions / Q000209:etiology; D004417:Dyspnea / Q000139:chemically induced; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007165:Immunosuppression Therapy; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011537:Pruritus / Q000139:chemically induced; D019172:Transplantation Conditioning; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D000975:Antioxidants; D014665:Vasodilator Agents; D000111:Acetylcysteine
N-acetylcysteine; acute kidney injury; hematopoietic stem cell transplantation; randomized controlled trial; urine neutrophil gelatinase-associated lipocalin