Overview of the renin-angiotensin system in diabetic nephropathy

Diabetes mellitus is a multifactorial hyperglycemic condition characterized by biochemical, molecular, and genetic variables, and leads to kidney dysfunction. Diabetic nephropathy (DN), referred to as diabetic kidney disease, is one of the major microvascular complications of diabetes, which is a major cause of end-stage renal disease and, consequently, high mortality. When DN occurs, it stimulates the renin-angiotensin system (RAS), one of the most significant indicators of developing renal impairment. Intrarenal RAS elements are upregulated in patients with DN, whereas systemic RAS elements are downregulated. Therefore, it is well accepted that the intra-renal RAS plays a key role in the onset of DN, characterized by the presence of protein in the urine and progressive decline in kidney function. RAS has two axes: 1- the renin, angiotensin-converting enzyme (ACE), angiotensin II (Ang II), and Ang II type 1 receptor (AT 1 R), 2- (ACE2, Ang 1-7, Ang 1-9, AT 2 receptor (AT 2 R), and Mas receptor (MasR). Blocking RAS with ACE inhibitors (ACEIs) and Ang II receptor blockers (ARBs) is currently a conventional therapy to protect the kidneys and inhibit DN progression and development in people with type 1 and type 2 diabetes.