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

INTRODUCTION: Patients with chronic kidney disease (CKD) receiving dialysis (CKD-5D) are at increased risk for tuberculosis (TB), which 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 and 2025, universal long-term IPT was administered to patients with CKD-5D (= 182) receiving dialysis in Gqeberha, South Africa (post-IPT cohort), an area with high TB rates. The incidence of TB post-IPT was compared with a historical CKD-5D cohort (pre-IPT) from the same unit (= 111). Primary outcomes included incident TB and adverse events attributable to IPT.

RESULTS: The incidence of TB (per 100,000 person-years [pys]) in the post-IPT cohort was 367, versus 4505 pre-IPT (92% relative risk reduction,< 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 hemodialysis (HD). Liver injury was noted in 6 patients (3.3%), of whom 2 continued IPT successfully. Overall, 17 patients (9.3%) required discontinuation of IPT because of side effects attributed to IPT (PNP = 12, liver injury = 4, and pancreatitis = 1). No deaths were attributed to IPT.

CONCLUSION: Long-term IPT significantly reduced the incidence of TB in a high-risk cohort with CKD-5D. IPT was safe and well-tolerated, with < 10% of patients discontinuing therapy because of adverse events, which were generally mild and reversible. These findings provide strong real-world evidence supporting IPT use in TB-endemic dialysis populations.