Emerging roles of cannabinoid pathways in renal injury and repair.

Chronic kidney disease (CKD) is a significant health problem around the world. It can progress towards end-stage renal disease (ESRD), in which the current therapeutic options are dialysis and kidney transplant, which have several challenges in therapy compliance and finding a donor. There is a crosstalk between high blood pressure, diabetes, and obesity, which are the leading causes of CKD. The increased prevalence of these conditions, plus the ageing population, highlights the importance of finding new therapies to prevent and stop the progression of CKD. At the cellular level, CKD is characterized by the progressive loss of podocytes in the kidney glomeruli, reducing their filtration capacity. Other hallmarks of CKD are also part of acute kidney injury (AKI) pathogenesis, and both conditions are interlinked. The renal system expresses cannabinoid receptor types 1 and 2 (CB1 and CB2, respectively). There is evidence in animal models that targeting the cannabinoid receptors could modulate the progression of CKD and AKI. The role of cannabinoid signalling has not been sufficiently explored; several receptors that are not fully characterized have emerged as putative cannabinoid receptors (i.e., GPR55, GPR18, and GPR119), and some have been implicated in kidney pathophysiology. Moreover, cannabinoid receptors also interact and/or regulate other receptors (e.g., AT1, TRPV1, and PPARγ). Thus, there are several open questions regarding the role that cannabinoid signalling may play in the context of kidney diseases. In this mechanistic review, we examined the pharmacological actions of classic and emerging cannabinoid receptors on the renal system to identify potential therapeutic targets for kidney disease.