Circulating NLRP3 Inflammasome Activation Is Associated With Sepsis-Associated Acute Kidney Injury and Disease...

Sepsis-associated acute kidney injury (SA-AKI) is a severe and prevalent complication in critically ill patients, characterized by high mortality and a lack of reliable biomarkers that reflect inflammatory pathway activation and disease severity. Although the NLRP3 inflammasome is known to mediate inflammatory responses, pyroptosis, and renal injury, its clinical relevance in human SA-AKI remains poorly defined. This study aimed to characterize the expression profiles, dynamic trajectories, and clinical associations of circulating NLRP3 inflammasome components in patients with SA-AKI.

Thirty adult patients with sepsis (13 with SA-AKI and 17 without AKI) were prospectively and consecutively enrolled. Sepsis was defined according to the Sepsis-3 consensus criteria, whereas AKI was diagnosed and staged exclusively using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Serum protein levels of NLRP3, ASC, caspase-1, cleaved caspase-1, IL-1β, and IL-18, and transcript levels of NLRP3, ASC, and caspase-1, were determined on days 1, 3, 5, and 7 after enrollment using ELISA and quantitative real-time PCR. Statistical analyses included group comparisons, Spearman rank correlations, linear mixed-effects models, and exploratory receiver operating characteristic (ROC) analyses to assess concurrent group discrimination. Because samples were collected post-classification, these analyses describe post-diagnostic expression kinetics rather than prediction of future AKI onset.

The expression of NLRP3 inflammasome-related molecules was significantly upregulated in the SA-AKI group and correlated with renal dysfunction and elevated illness-severity scores (SOFA and APACHE II). Exploratory ROC analyses suggested strong discrimination of concurrent AKI status for ASC, caspase-1, and NLRP3 transcript levels, with the strongest overall performance observed on day 3. These estimates are hypothesis-generating because of the small sample size and post-classification sampling.

The NLRP3 inflammasome pathway is prominently activated in patients with SA-AKI and is closely associated with renal dysfunction and systemic illness severity. Circulating components of this pathway are candidate biomarkers of concurrent SA-AKI, but their ability to predict AKI onset or prognosis requires validation in larger prospective cohorts sampled before AKI develops.