Inflammatory factors and hypertensive nephropathy: A bidirectional 2-sample Mendelian randomization study.

Hypertensive nephropathy (HTN) is a major public health concern worldwide. This study aims to investigate the potential causal relationships between inflammatory factors and HTN, as well as to identify possible underlying biological pathways. Using genome-wide association study data from large publicly available population cohorts, we applied a bidirectional 2-sample Mendelian randomization approach to investigate whether 91 inflammatory factors influence the risk of HTN. Additionally, we examined whether HTN has a potential causal effect on the levels of these inflammatory factors. Finally, we performed pathway enrichment analysis to explore the underlying biological pathways involved in these associations. Mendelian randomization results indicated that interleukin-20 receptor subunit alpha, caspase 8, CUB domain-containing protein 1, and stem cell factor were associated with a reduced HTN, while interleukin-18 receptor 1, leukemia inhibitory factor, oncostatin-M, and interferon-gamma were associated with an increased HTN. Pathway enrichment analysis further identified several biological pathways potentially involved in the development of HTN. This study provides evidence for causal relationships between multiple inflammatory factors and HTN, offering valuable insights that may inform disease management strategies and policy development related to HTN.