Untangling the Knot in Diabetic Nephropathy: The Unanticipated Role of Glycocalyx in the Antiproteinuric Effect of Endothelin Receptor Antagonists.

Abstract

Diabetes is a devastating disease that is imposing itself as one of the largest health emergencies of the 21st century, and high blood glucose is the third-highest risk factor for premature mortality (1). In 2015, almost 5 million people aged 20–79 years died from diabetes and its related complications, which accounted for almost 15% of the overall causes of mortality among people in this age-group (1). With no effective prevention and management programs, the incidence of diabetes and its complications is dramatically increasing worldwide, imposing a substantial impact on the economy. Diabetic nephropathy (DN) affects 30–40% of patients with diabetes (2) and induces a progressive deterioration of renal function. Albuminuria independently associates with increased vascular mortality and morbidity in patients with diabetes (3), in patients with hypertension (4), and in the general population (5), and therefore is not only a sign of renal impairment and a key pathogenic element of renal disease progression but also a marker of more generalized vascular damage. Many studies have linked albuminuria with cardiovascular disease (CVD). A linear relationship was observed between albumin excretion and CVD risk (6), but the exact significance and mechanism of such a relationship are not yet understood. Microalbuminuria not only denotes renal capillary damage but also represents an early biological marker of vascular injury (7). Endothelial dysfunction has been implicated …