{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:55:41Z","timestamp":1789052141680,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T00:00:00Z","timestamp":1676851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Israel Science Foundation (ISF)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Renal ischemia\u2013reperfusion (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 \u2018traditional\u2019 IR-injury \u2018preventive drugs\u2019, our data support future research on the role of the ECS and its manipulation in renal IR.<\/jats:p>","DOI":"10.3390\/ijms24044216","type":"journal-article","created":{"date-parts":[[2023,2,20]],"date-time":"2023-02-20T06:37:59Z","timestamp":1676875079000},"page":"4216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Systemic Changes in Endocannabinoids and Endocannabinoid-like Molecules in Response to Partial Nephrectomy-Induced Ischemia in Humans"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0247-742X","authenticated-orcid":false,"given":"Ariel","family":"Rothner","sequence":"first","affiliation":[{"name":"Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Gov","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6905904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0307-4350","authenticated-orcid":false,"given":"Liad","family":"Hinden","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2598-0119","authenticated-orcid":false,"given":"Alina","family":"Nemirovski","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0948-0093","authenticated-orcid":false,"given":"Joseph","family":"Tam","sequence":"additional","affiliation":[{"name":"Obesity and Metabolism Laboratory, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barak","family":"Rosenzweig","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6905904, Israel"},{"name":"Department of Urology, Chaim Sheba Medical Center, Ramat Gan 5265601, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.eururo.2019.02.011","article-title":"European Association of Urology Guidelines on Renal Cell Carcinoma: The 2019 Update","volume":"75","author":"Ljungberg","year":"2019","journal-title":"Eur. 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