Endocannabinoid System and the Kidneys: From Renal Physiology to Injury and Disease

Abstract

Introduction: As the prevalence of kidney disease continues to rise worldwide, there is accumulating evidence that kidney injury and dysfunction, whether acute or chronic, is associated with major adverse outcomes, including mortality. Meanwhile, effective therapeutic options in the treatment of acute kidney injury (AKI) and chronic kidney disease (CKD) have been sparse. Many of the effective treatments that are routinely utilized for different pathologies in patients without kidney disease have failed to demonstrate efficacy in those with renal dysfunction. Hence, there is an urgent need for discovery of novel pathways that can be targeted for innovative and effective clinical therapies in renal disease states. Discussion: There is now accumulating evidence that the endocannabinoid (EC) system plays a prominent role in normal renal homeostasis and function. In addition, numerous recent studies have described mechanisms through which alteration in the EC system can contribute to kidney damage and disease. These include a potential role for cannabinoid receptors in tubulo-glomerular damage and fibrosis, which are common features of AKI, interstitial nephritis, glomerulopathy, and other conditions leading to AKI and CKD. Conclusion: These findings suggest that manipulating the EC system may be an effective therapeutic strategy for the treatment of kidney disease and injury. However, further mechanistic studies are needed to fully delineate the role of this system in various conditions affecting the kidneys. Furthermore, while most of the current literature is focused on the role of the EC system as a whole in renal pathophysiology, future studies will also need to clarify the contribution of each component of this system, including the EC mediators, in the pathogenesis of kidney disease and their potential role as part of a therapeutic strategy.

Keywords: acute kidney injury; chronic kidney disease; endocannabinoid; fibrosis; inflammation; nephropathy.

FIG. 1.

Roles of the endocannabinoid system in healthy kidney. Images adapted from Servier Medical Art “Kidney” licensed under CC 3.0, https://smart.servier.com/smart_image/kidney

FIG. 2.

Impact of various kidney disease models on receptors and ligands of the endocannabinoid system. Images adapted from Servier Medical Art “Kidney” licensed under CC 3.0, https://smart.servier.com/smart_image/kidney