Systemic Changes in Endocannabinoids and Endocannabinoid-like Molecules in Response to Partial Nephrectomy-Induced Ischemia in Humans

Renal ischemia-reperfusion (IR), a routine feature of partial nephrectomy (PN), can contribute to the development of acute kidney injury (AKI). Rodent studies show that the endocannabinoid system (ECS) is a major regulator of renal hemodynamics and IR injury; however, its clinical relevance remains to be established. Here, we assessed the clinical changes in systemic endocannabinoid (eCB) levels induced by surgical renal IR. Sixteen patients undergoing on-clamp PN were included, with blood samples taken before renal ischemia, after 10 min of ischemia time, and 10 min following blood reperfusion. Kidney function parameters (serum creatinine (sCr), blood urea nitrogen (BUN), and serum glucose) and eCB levels were measured. Baseline levels and individual changes in response to IR were analyzed and correlation analyses were performed. The baseline levels of eCB 2-arachidonoylglycerol (2-AG) were positively correlated with kidney dysfunction biomarkers. Unilateral renal ischemia increased BUN, sCr, and glucose, which remained elevated following renal reperfusion. Renal ischemia did not induce changes in eCB levels for all patients pooled together. Nevertheless, stratifying patients according to their body mass index (BMI) revealed a significant increase in N-acylethanolamines (anandamide, AEA; N-oleoylethanolamine, OEA; and N-palmitoylethanolamine, PEA) in the non-obese patients. No significant changes were found in obese patients who had higher N-acylethanolamines baseline levels, positively correlated with BMI, and more cases of post-surgery AKI. With the inefficiency of 'traditional' IR-injury 'preventive drugs', our data support future research on the role of the ECS and its manipulation in renal IR.

Automated summary

Renal ischemia-reperfusion (IR) during partial nephrectomy (PN) can lead to acute kidney injury (AKI). The endocannabinoid system (ECS) is known to regulate renal hemodynamics and IR injury in rodent studies, but its clinical relevance is still unclear. This study assessed the changes in systemic endocannabinoid (eCB) levels induced by surgical renal IR in 16 patients. Baseline eCB levels were positively correlated with kidney dysfunction biomarkers. While renal ischemia did not affect eCB levels in all patients, non-obese patients showed an increase in N-acylethanolamines. Obese patients had higher baseline levels of N-acylethanolamines, which were positively correlated with BMI and had more cases of post-surgery AKI. These findings suggest further research on the role of the ECS in renal IR is warranted, considering the inefficiency of traditional preventative drugs.