{"doi":"10.3390/pharmaceutics17040516","title":"N-Acetylcysteine to Reduce Kidney and Liver Injury Associated with Drug-Resistant Tuberculosis Treatment","abstract":"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.","journal":"Pharmaceutics","year":2025,"id":550473,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9623,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":699408,"name":"Happiness Mvungi","orcid":"0000-0001-6527-4887","position":1,"is_corresponding":false},{"id":1446076,"name":"Kassim Salim","orcid":null,"position":2,"is_corresponding":false},{"id":1445690,"name":"Oscar Leonard Kaswaga","orcid":"0000-0003-1114-9305","position":3,"is_corresponding":false},{"id":699410,"name":"Peter M. Mbelele","orcid":"0000-0002-2693-187X","position":4,"is_corresponding":false},{"id":930151,"name":"Alphonce Liyoyo","orcid":null,"position":5,"is_corresponding":false},{"id":1445691,"name":"Hadija Semvua","orcid":"0000-0002-1352-5899","position":6,"is_corresponding":false},{"id":1446077,"name":"Athumani Ngoma","orcid":null,"position":7,"is_corresponding":false},{"id":365125,"name":"Scott K. Heysell","orcid":"0000-0002-2040-0293","position":8,"is_corresponding":false},{"id":365122,"name":"Stellah Mpagama","orcid":"0000-0002-0660-6930","position":9,"is_corresponding":false},{"id":1445689,"name":"Idu Meadows","orcid":"0009-0008-7508-6394","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:54:16.596730Z","pmid":"40284511","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}