Therapeutic potential of pro-resolving mediators in diabetic kidney disease

Abstract

Renal microvascular disease associated with diabetes [Diabetic kidney disease - DKD] is the leading cause of chronic kidney disease. In DKD, glomerular basement membrane thickening, mesangial expansion, endothelial dysfunction, podocyte cell loss and renal tubule injury contribute to progressive glomerulosclerosis and tubulointerstitial fibrosis. Chronic inflammation is recognized as a major pathogenic mechanism for DKD, with resident and circulating immune cells interacting with local kidney cell populations to provoke an inflammatory response. The onset of inflammation is driven by the release of well described proinflammatory mediators, and this is typically followed by a resolution phase. Inflammation resolution is achieved through the bioactions of endogenous specialized pro-resolving lipid mediators (SPMs). As our understanding of SPMs advances 'resolution pharmacology' based approaches using these molecules are being explored in DKD.

Keywords: Glomerulosclerosis; Hyperglycemia; Inflammation; Lipoxins; Polyunsaturated fatty acids; Specialized pro-resolving mediators; Tubulointerstitial fibrosis.