Relationship between selected microRNAs, pentraxin 3 and uromodulin in pathophysiology of septic acute kidney injury

BACKGROUND: Acute kidney injury (AKI) is a common complication of sepsis and is associated with increased morbidity and mortality in critically ill patients. Combined assessment of serum pentraxin 3 (PTX3), uromodulin (UMOD), and circulating microRNAs (miRNAs) may improve understanding of the pathophysiology of septic AKI. METHODS: In this study, 81 critically ill adults with sepsis were stratified into AKI and non-AKI groups, and 90 healthy volunteers served as controls. Blood samples were collected on days 1 and 4 after the diagnosis of sepsis. PTX3 and UMOD concentrations were measured by ELISA, and miRNA expression was assessed by RT-qPCR. Seven miRNAs were validated, and their target genes associations were analyzed using TargetScanHuman8.0. RESULTS: PTX3 and UMOD distinguished healthy controls from septic patients, whereas only PTX3 differentiated patients with AKI from non-AKI. Baseline PTX3 and procalcitonin were independently associated with AKI on days 1 and 4. In AKI group, four analyzed miRNAs showed significant intercorrelations on day 1; however, these weakened by day 4 with changes in renal function and sepsis. Selected miRNAs were interpreted in the context of predicted target genes and pathways related to NF-κB signaling, renal cell apoptosis, and autophagy/mitophagy, rather than as direct causal regulators demonstrated in this study. CONCLUSIONS: PTX3, UMOD, and selected miRNAs provide complementary information on septic AKI and support a multifactorial concept of its pathophysiology.The study was registered at ClinicalTrials.gov (ID: NCT06498336) on May 2, 2024 to March 31, 2026.