Could NAC protect kidneys during drug-resistant TB treatment?

Drug-resistant tuberculosis remains a major global health challenge, and although new drug classes and shorter regimens have improved treatment time, side effects and organ damage are still common. To explore whether a familiar medicine might lower those risks, Stellah Mpagama and colleagues ran a randomized controlled trial at Kibong’oto Infectious Disease Hospital in Tanzania (PACTR202007736854169). The study tested N-acetylcysteine (NAC), a compound with prior evidence of reducing kidney and liver toxicity in other medical settings, in people receiving an all-oral standardized rifampin-resistant regimen for pulmonary tuberculosis. Sixty-six adults were enrolled (mean age 47±12 years; 80% male) and randomly assigned into three equal groups of 22: standard treatment alone, standard treatment plus NAC 900 mg once daily, or standard treatment plus NAC 900 mg twice daily. Treatment and monitoring continued for six months. The research team tracked adverse events and organ-specific injury closely to see whether adding NAC could make the difficult toxicities of rifampin-resistant therapy less frequent or less severe.

Participants were followed monthly for adverse events (AEs), with kidney outcomes classified using the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and liver outcomes graded by the National Cancer Institute Common Terminology Criteria for Adverse Events. The investigators used incident ratios and Kaplan-Meier curves to compare how often events occurred and how quickly they appeared across the three groups. Across the trial there were 158 recorded AEs: 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 seen in 4 patients in the standard group, 2 in the NAC 900 mg daily group, and 3 in the NAC 900 mg twice daily group. Renal toxicity was more common in the standard group than in the combined NAC groups (45% vs. 23%; p=0.058) and tended to occur sooner in the standard group (χ2 = 3.199; p=0.074). Liver injury events were rare in all groups.

The trial did not find a statistically significant reduction in overall adverse events when NAC was added to rifampin-resistant tuberculosis treatment, but the data showed an important pattern: fewer and later-onset kidney problems in patients who received NAC. Because renal toxicity can force treatment changes or interruptions, a therapy that lowers that risk could meaningfully improve how tolerable rifampin-resistant regimens are for patients. The study tested two dosing strategies—NAC 900 mg daily and NAC 900 mg twice daily—over six months and provides controlled evidence that supports further investigation. The findings are preliminary and not definitive, but they point toward NAC as a potentially protective, low-cost adjunct that merits larger, more definitive trials to confirm whether the kidney-sparing trends hold and to determine whether specific dosing strategies work best without introducing other harms.