Endocannabinoid responses to relief of obstruction in acute injured kidney: a prospective observational study

Background: The endocannabinoid system (ECS) regulates homeostasis, inflammation, and organ-specific function. In the kidney, ECS activity modulates renal hemodynamics, and its overactivation is linked to chronic injury. However, the importance of the ECS involvement in acute kidney injury (AKI) remains unclear. This study aimed to characterize changes in circulating endocannabinoid (eCB) levels before and after relief of upper urinary tract obstruction (UUTO), to better understand ECS dynamics during acute renal dysfunction. These findings may inform the development of novel biomarkers and therapeutic targets for renal injury. Objectives: To characterize changes in circulating eCB levels before and after relief of UUTO, and to compare responses between patients with and without AKI. Design: Prospective observational cohort with paired, within-person sampling. Methods: Patients presenting to the emergency department with acute renal colic due to obstructive urolithiasis who underwent kidney decompression within 24 h were prospectively enrolled. Clinical, laboratory, and imaging data plus paired blood samples for eCB analysis were collected pre and post-drainage. Patients were divided into two groups: those who had AKI at presentation, and non-AKI controls. Serum eCBs were quantified, and fold changes compared using nonparametric analysis. Results: Twenty-two patients enrolled (10 had AKI and 12 served as non-AKI controls). Serum N-acylethanolamines (NAEs) showed divergent responses between the two groups. In AKI, N-arachidonoylethanolamine (AEA), N-palmitoylethanolamine, and N-oleoylethanolamine increased following drainage (p = 0.06, 0.008, 0.08). In contrast, patients without AKI demonstrated a reduction in NAE levels, with a significant AEA drop (p = 0.03) after obstruction relief. Notably, the fold-change in NAE levels post-drainage was significantly higher in patients with AKI compared to those without AKI. Conclusion: Circulating NAEs increase following relief of obstruction in patients with acute renal dysfunction, suggesting a potential role for ECS activation in the pathophysiology of UUTO-induced kidney injury. These findings highlight the ECS as a promising target for further investigation as a possible therapeutic avenue in AKI. Trial registration: Not applicable.