Diabetes is one of the most common metabolic conditions that can significantly impair the overall quality of life. Diabetic nephropathy is a diabetes-associated renal damage condition and one of the most common diabetes-induced renal complications. The hyperglycaemia associated with diabetes is considered one of the key factors associated with the renal damage. The endocannabinoid system is a complex biological process involved in various physiological activities, while its impairment is directly associated with numerous pathological conditions as well. The components of the endocannabinoid system are widely distributed in the body, including in the renal tissues. Hence, alteration in the renal endocannabinoid system is associated with chronic kidney dysfunction conditions. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide that is produced on demand by almost all the cells in the body. Due to its myriad molecular targets, PEA is able to produce potent anti-inflammatory and antioxidant effects. While much focus has highlighted the potential therapeutic efficacy of exogenous PEA therapy in various painful conditions, its beneficial effect in diabetes-induced renal damage conditions is still largely unexplored. The current review study aimed to highlight the potential effect of PEA therapy in renal damage conditions, with particular emphasis on the molecular mechanisms involved for the same. The current review supports the use of PEA in diabetic conditions due to its myriad protective effects on renal tissues; thereby, the need for well-designed clinical studies to establish PEA’s renal protective efficacy in the diabetic population is warranted.

Diabetes, Chronic kidney disease, Palmitoylethanolamide, PPAR, TRPV, Nephropathy, Narrative review.