Safety and Effectiveness of Long-Term Isoniazid Treatment for the Prevention of Tuberculosis in High-Risk Dialysis Patients

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Introduction Chronic kidney disease patients receiving dialysis (CKD-5D) are at increased risk for tuberculosis (TB), which also significantly heightens the risk of mortality. Long-term isoniazid prevention therapy (IPT) to prevent TB is a promising strategy, although the safety and effectiveness of the approach in this high-risk population is unknown. Methods Between 2019-2025, universal long-term IPT was administered to CKD-5D patients (N=182) receiving dialysis in Gqeberha, South Africa (post-IPT cohort), an area with high TB rates. The incidence of TB post-IPT was compared to a historical CKD-5D cohort (pre-IPT) from the same unit (N=111). Primary outcomes included incident TB and adverse events attributable to IPT. Results The incidence of TB (per 100000 person-years) in the post-IPT cohort was 367, versus 4505 pre-IPT (92% relative risk reduction, p <0.001). During IPT, 32 patients (17.6%) developed symptoms of peripheral neuropathy (PNP), of whom 20 (62.5%) resolved fully with increased pyridoxine dosing. PNP was associated with older age and haemodialysis. Liver injury was noted in six patients (3.3%), of whom two continued IPT successfully. Overall, seventeen patients (9.3%) required discontinuation of IPT due to side effects attributed to IPT (PNP=twelve, liver injury=four, and pancreatitis=one). No deaths were attributed to IPT. Conclusion Long-term IPT significantly reduced the incidence of TB in a high-risk cohort of CKD-5D. IPT was safe and well tolerated, with fewer than 10% of patients discontinuing therapy due to adverse events, which were generally mild and reversible. These findings provide strong real-world evidence supporting IPT use in TB-endemic dialysis populations.

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