Mapping the knowledge landscape and identifying frontiers of mitochondrial dysfunction in sepsis-associated acute...

Mitochondrial dysfunction has been recognized as a central pathogenic event and is under active investigation as a candidate therapeutic target in sepsis-associated acute kidney injury (SA-AKI). This study aims to employ multi-tool bibliometric analysis to systematically map the four-decade intellectual landscape of this field, thereby identifying emerging research hotspots and outlining priority-setting directions for future pharmacological investigation. Because publication and citation metrics quantify scholarly attention rather than therapeutic efficacy, the pathways highlighted here reflect research trends and priority-setting signals, not established therapeutic targets. A comprehensive literature retrieval was conducted across PubMed, Web of Science, and Scopus up to March 18, 2026. Following rigorous data cleaning, 837 publications were analyzed using CiteSpace, VOSviewer, and the bibliometrix R package to visually evaluate publication trends, knowledge networks, and evolving research hotspots. Cumulative publication output exhibits sustained exponential growth (R² = 0.997), accelerating significantly post-2010. China and the USA dominate global productivity, though institutional collaboration networks reveal pronounced regional clustering. Notably, publication hubs have transitioned significantly from traditional critical care journals to molecular and pharmacological journals, consistent with a shifting emphasis of scholarly attention toward molecular and pharmacological research themes. Keyword and citation burst analyses suggest that the research frontier has evolved from broad physiological observations to specific subcellular executioners. Mitochondria-mediated programmed cell death (apoptosis, pyroptosis, and ferroptosis) and oxidative stress have become the most prominent bibliometric hotspots and candidate pharmacological targets. The field of SA-AKI research has shown a pronounced, publication-driven shift from clinical phenotyping to the target-driven molecular deconstruction of mitochondrial damage; we emphasize that this result reflects research priorities, not proven therapeutic efficacy of these targets. To overcome current translational bottlenecks and off-target effects of existing agents, future drug development should transition from isolated in vitro models toward clinical multi-omics validation. Developing innovative targeted delivery systems (such as engineered nanomaterials and exosomes) and multi-target synergistic therapies will need rigorous empirical testing to determine whether they can precisely mitigate the complex SA-AKI "mitochondrial storm".