Dyslipidemia promotes the progression of diabetic nephropathy, and lipid-lowering therapies such as statins provide protective effects on renal function and cardiovascular outcomes.
Does lipid-lowering therapy improve renal function and reduce albuminuria in patients with diabetic nephropathy?
Dyslipidemia plays a critical role in the progression of diabetic nephropathy, and lipid-lowering therapies such as statins may provide renal protection through Rho-kinase inhibition.
Diabetic nephropathy (DN) not only is a major cause of end-stage renal disease (ESRD) in developing and developed countries but also plays a critical role as a risk factor for cardiovascular disease. The pathogenesis of DN is multifactorial and remains to be elucidated. It is well known that dyslipidemia is frequently complicated with diabetes. Recently, dyslipidemia has been recognized to be involved in the progression of DN. In general, diabetic dyslipidemia is caused by impaired action of lipoprotein lipase (LPL) that is localized to the endothelial cells, resulting in increased serum levels of increased triglyceride (TG) and decreased high-density lipoprotein cholesterol (HDL-C). Smaller size and modified low-density lipoprotein (LDL), such as glycated and oxidized LDL, play important roles to induce vascular and renal cellular dysfunction. Previous studies demonstrated that dyslipidemia enhances macrophage infiltration and excessive extracellular matrix (ECM) production in the glomeruli under diabetic conditions, leading to the development of DN. Clinical studies have demonstrated that lipid-lowering therapy shows a protective effect on the renal function. It is well known that statins reduce albuminuria in patients with DN. A series of our studies indicated that this effect is mediated by Rho-kinase inhibition. Rho-kinase plays a key role in the pathogenesis of DN by activating the inflammatory pathway, including oxidative stress, NF-κB, and hypoxia inducible factor (HIF)-1. Intriguingly, Rho-kinase inhibitors have been shown to attenuate glomerulosclerosis as well as atherosclerosis. Therefore, Rho-kinase could be a promising therapeutic target for both DN and cardiovascular disease.
Kawanami et al. (Thu,) conducted a review in Diabetic nephropathy with dyslipidemia. Lipid-lowering therapy was evaluated. Dyslipidemia promotes the progression of diabetic nephropathy, and lipid-lowering therapies such as statins provide protective effects on renal function and cardiovascular outcomes.