Laboratory of Diabetic Nephropathy, Department of Medical Sciences, University of Turin, Turin, Italy.
Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
Kidney Int. 2018 Aug;94(2):252-258. doi: 10.1016/j.kint.2018.01.024. Epub 2018 Apr 27.
The endogenous cannabinoids anandamide and 2-arachidonoylglycerol bind to the cannabinoid receptors of type 1 and 2. These receptors are also the binding sites for exogenous, both natural and synthetic, cannabinoids that are used for recreation purposes. Until recently, cannabinoids and cannabinoid receptors have attracted little interest among nephrologists; however, a full endocannabinoid system (ECS) is present in the kidney and it has recently emerged as an important player in the pathogenesis of diabetic nephropathy, drug nephrotoxicity, and progressive chronic kidney disease. This newly established role of the ECS in the kidney might have therapeutic relevance, as pharmacological modulation of the ECS has renoprotective effects in experimental animals, raising hope for future potential applications in humans. In addition, over the last years, there has been a number of reported cases of acute kidney injury (AKI) associated with the use of synthetic cannabinoids that appear to have higher potency and rate of toxicity than natural Cannabis. This poorly recognized cause of renal injury should be considered in the differential diagnosis of AKI, particularly in young people. In this review we provide an overview of preclinical evidence indicating a role of the ECS in renal disease and discuss potential future therapeutic applications. Moreover, we give a critical update of synthetic cannabinoid-induced AKI.
内源性大麻素如花生四烯酸乙醇胺和 2-花生四烯酰甘油与 1 型和 2 型大麻素受体结合。这些受体也是外源性大麻素（包括天然和合成大麻素）的结合位点，这些大麻素被用于娱乐目的。直到最近，肾病学家对大麻素和大麻素受体的关注甚少；然而，肾脏中存在完整的内源性大麻素系统（ECS），并且最近它已成为糖尿病肾病、药物肾毒性和进行性慢性肾病发病机制中的重要参与者。ECS 在肾脏中的这种新确立的作用可能具有治疗相关性，因为 ECS 的药理学调节在实验动物中具有肾脏保护作用，这为未来在人类中的潜在应用带来了希望。此外，在过去几年中，有许多报道的与使用合成大麻素相关的急性肾损伤（AKI）的病例，这些病例似乎比天然大麻具有更高的效力和毒性。这种未被充分认识的肾损伤原因应在 AKI 的鉴别诊断中考虑，尤其是在年轻人中。在这篇综述中，我们提供了临床前证据的概述，表明 ECS 在肾脏疾病中的作用，并讨论了潜在的未来治疗应用。此外，我们对合成大麻素诱导的 AKI 进行了批判性更新。
