Obesity and Diabetes are chronic diseases that are now reaching epidemic proportions. Both have been described as catalysts for a number of conditions, most notably cardiovascular disease, retinal disease and chronic kidney disease (CKD). The latter is the single most frequent cause of end-stage-renal disease (ESRD) in Western societies. CKD affects approximately 30% of patients with diabetes, and is strongly associated with cardiovascular morbidity and mortality. It also develops early in the course of obesity and the metabolic syndrome. In fact, obese individuals have a threefold greater risk to develop ESRD. CKD and ESRD impose a substantial burden on global health-care resources, and despite successful intervention trials, progressive loss of renal function and ESRD still occurs in many patients. Thus, new strategies for therapy are needed.
Altered activation of the endocannabinoid system has been recently demonstrated in various diabetic complications, including CKD. CB1 receptors are expressed in different kidney cells and their blockade has the potential to reverse CKD in animal models. However, there remain a number of pertinent issues that will eventually enhance our understanding of the role of CB1 receptor and its therapeutic potential in CKD. For instance, (i) To what extent are the improved metabolic effects mediated globally, peripherally or via a specific cell type within the kidney? and (ii) To what extent are the observed improvements in renal damage mediated by a specific organelle within the renal cells? These are critical questions with respect to developing a more specific drug for the diseased kidney.