Urinary Neutrophil Gelatinase-Associated Lipocalin as a Marker of Renal Function Decline and Mood Disorders in Chronic Stress Rodent Models

Chronic stress is associated with mood disorders and systemic organ dysfunction. The kidney's vulnerability to stress, along with the frequent overlap of renal diseases and neurological abnormalities, suggests a bidirectional interaction between the renal and nervous systems, though the mechanisms remain unclear. Our research investigates how chronic stress impacts this relationship. We hypothesize that an immune-inflammatory response may mediate the brain-kidney interaction under chronic stress. Here we utilized two rodent models previously linked to heightened behavioral emotionality: 1) chronic peripheral inflammatory pain [i.e., injections of complete Freund’s adjuvant (CFA) into the hind paw], and 2) chronic administration of corticosterone hemisuccinate (CORT) in drinking water. We measured Neutrophil Gelatinase-Associated Lipocalin (NGAL) protein levels in renal cortical tissue (immunofluorescence analysis) and urine (ELISA assay) as biomarkers of renal inflammation and injury. Additionally, NOD-like receptor protein 3 (NLRP3), a marker of neuroinflammatory responses and a key contributor to renal inflammation and fibrosis, was quantified in the renal cortical tissue of both models. Creatinine clearance was measured to estimate glomerular filtration rate (GFR) as an indicator of kidney function. Our results showed that NGAL expression in renal tissue increased and correlated with higher urinary NGAL levels in both models. These increases were associated with impaired renal function, reflected by reduced GFR. Moreover, we found a strong negative correlation between lower GFR and enhanced emotional behaviors (correlation coefficients: -0.90 for Control, -0.71 for CFA, and -0.45 for CORT). Immunofluorescence analysis revealed elevated NLRP3 expression in renal cortical tissue in both models. Overall, these findings support our hypothesis that chronic stress impairs kidney function and contributes to behavioral deficits. They further suggest that NLRP3 activation mediates the link between reduced kidney function and emotional abnormalities under chronic stress. In summary, we propose that urinary NGAL serves as a marker of impaired kidney function and emotional disturbances under chronic stress, highlighting NLRP3-mediated inflammation as a potential therapeutic target. This research was supported by Des Moines University IOER Research & Grant Awards #03-20-08 and #03-22-08 (VD and FDS). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.