Dual Renin-Angiotensin-Aldosterone System Inhibition for the Treatment of Diabetic Kidney Disease: Adverse Effects and Unfulfilled Promise

Abstract

Diabetic nephropathy (DN) is a major complication of diabetes mellitus (DM) affecting individuals with type 1 or type 2 DM and is the leading cause of chronic kidney disease and end-stage kidney disease (ESKD) in the USA. Estimates of disease burden are projected to increase, with prevalence of nearly one in five adults by 2050. The role of renin-angiotensin-aldosterone system (RAAS) inhibition in delaying the progression of DN utilizing angiotensin-converting enzyme inhibitors or angiotensin receptor blockers has been well established in multiple controlled trials. Given greater reduction of proteinuria with dual RAAS blockade compared to monotherapy alone, the potential benefit of dual therapy on progression of DN has been tested in three large randomized clinical trials. Unfortunately, results from these studies demonstrated lack of benefit of dual blockade on renal or cardiovascular outcomes in patients with diabetes. The overall objectives of this review are to provide both the rationale for dual blockade as potential therapy as well as review the literature of its use in patients with DN.

Ursolic Acid Attenuates High Glucose-Mediated Mesangial Cell Injury by Inhibiting the Phosphatidylinositol 3-Kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR) Signaling Pathway

“…The morbidity of diabetes has increased rapidly in the past decade. Diabetic nephropathy (DN) is a serious complication of diabetes and is the most common cause of end-stage renal disease [ 1 ]. A typical pathological feature of DN [ 2 ], glomerulosclerosis is primarily manifested as deposition of extracellular matrix (ECM) proteins, such as collagen and fibronectin (FN), in the mesangial area, and the resulting reduced filtration surface area of glomerular capillaries leads to further progression of DN [ 3 ].…”