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

Ariel Rothner, Tom Gov, Liad Hinden, Alina Nemirovski, Joseph Tam*, Barak Rosenzweig*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish
Article number4216
JournalInternational Journal of Molecular Sciences
Volume24
Issue number4
DOIs
StatePublished - 20 Feb 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • N-acylethanolamines
  • endocannabinoids
  • partial nephrectomy
  • renal ischemia reperfusion

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