N-Acetylcysteine to Reduce Kidney and Liver Injury Associated with Drug-Resistant Tuberculosis Treatment

Background: New drug classes and regimens have shortened the treatment duration for drug-resistant tuberculosis, but adverse events (AEs) and organ toxicity remain unacceptably common. N-acetylcysteine (NAC) has demonstrated potential in reducing kidney and liver toxicity in other clinical settings, but efficacy in drug-resistant tuberculosis treatment has not been rigorously evaluated. Method: A randomized controlled trial was conducted at Kibong'oto Infectious Diseases Hospital in Tanzania to assess the efficacy of NAC in reducing AEs in patients undergoing rifampin-resistant pulmonary tuberculosis treatment. Participants received an all-oral standardized rifampin-resistant regimen alone, with NAC 900 mg daily, or NAC 900 mg twice daily for 6 months. AEs, severe AEs, and renal and liver toxicity were monitored monthly and classified according to the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and National Cancer Institute Common Terminology Criteria for Adverse Events. Incident ratios and Kaplan-Meier curves were employed to compare group event occurrences. Results: A total of 66 patients (mean age 47 ± 12 years; 80% male) were randomized into three groups of 22. One hundred and fifty-eight AEs were recorded: 52 (33%) in the standard treatment group, 55 (35%) in the NAC 900 mg daily group, and 51 (32%) in the NAC 900 mg twice-daily group (p > 0.99). Severe AEs were observed in four patients in the standard group, two in the NAC 900 mg daily group, and three in the NAC 900 mg twice-daily group. Renal toxicity was more prevalent in the standard treatment group compared to those that received NAC (45% vs. 23%; p = 0.058), with a shorter onset of time to toxicity (χ² = 3.199; p = 0.074). Liver injury events were rare across all groups. Conclusion: Among Tanzanian adults receiving rifampin-resistant tuberculosis treatment, NAC did not significantly reduce overall AEs but demonstrated important trends in reducing renal toxicity.