Mapping the future: bibliometric insights into ferroptosis and diabetic nephropathy

Diabetic nephropathy (DN), a leading cause of end-stage renal disease, exerts a substantial burden on healthcare systems globally. Emerging evidence highlights ferroptosis - an iron-dependent form of cell death driven by lipid peroxidation and glutathione depletion - as a critical contributor to DN progression via oxidative stress, tubular injury, and glomerular dysfunction. Despite increasing research interest, a comprehensive synthesis of research trends and mechanistic insights is lacking.

This study integrated bibliometric analysis with a mechanistic review to map the evolving ferroptosis landscape in DN, identify research hotspots, and propose future directions for therapeutic development.

In total, 86 publications (2018-2023) were retrieved from the Web of Science Core Collection and analyzed using CiteSpace and VOSviewer. Co-occurrence networks, citation trends, and keyword bursts were examined to delineate global contributions, collaborative networks, and emerging themes.

Annual publication numbers surged 12-fold after 2020, with China contributing the highest proportion (60.4%), and led by institutions such as Zhengzhou University. The United States of America and Germany showed high centrality in collaborative networks. Key research themes included glutathione peroxidase 4 (GPX4)-mediated antioxidant defenses, acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated lipid remodeling, and iron dysregulation. Frontiers in Endocrinology (nine articles) and Free Radical Biology and Medicine (highest citation count: 171) emerged as pivotal publication platforms. Mechanistic analyses identified three ferroptosis defense axes (GPX4, FSP1/CoQ10, and GCH1/BH4) and cell type-specific vulnerabilities in tubular, podocyte, and endothelial cells. Preclinical agents, including ginkgolide B (GB) and dapagliflozin, effectively restored iron homeostasis and attenuated oxidative damage.

Ferroptosis is a promising therapeutic target for DN, yet its clinical translation remains in its infancy. Future efforts should prioritize large-scale clinical trials, single-cell mechanistic profiling, and interdisciplinary integration to bridge molecular insights with precision therapies. This study provides a roadmap for advancing ferroptosis-targeted interventions for DN, emphasizing global collaborations and biomarker-driven strategies.