Airi Kimura

Diabetic nephropathy is a major challenge in medicine. While a variety of mechanisms underlie the onset and progression of diabetic nephropathy, oxidative stress is critical because it promotes inflammation and creates a vicious cycle that induces podocyte injury, extracellular matrix accumulation, glomerulosclerosis, epithelial–mesenchymal transition, tubular atrophy, and proteinuria. There are various treatments for diabetic nephropathy, and each has its own limitations. Although the exact mechanisms by which polyphenols suppress diabetic nephropathy have not been elucidated, they may have antioxidant, anti-inflammatory, antifibrotic, and/or anti-apoptotic effects. They may also suppress endoplasmic reticulum stress and ameliorate mitochondrial dysfunction and dyslipidemia. Dietary polyphenols may be able to prevent the onset and slow the progression of diabetic nephropathy; they include resveratrol, quercetin, isoflavones, catechins, and anthocyanidins and have antioxidant, anti-inflammatory, antifibrotic, and anti-apoptotic effects through multiple molecular targets. Furthermore, they have shown few side effects. However, further research is needed to fully elucidate the molecular mechanisms by which polyphenols exert their effects and to clarify their optimal therapeutic use. In this review, we summarize reports published in the past five years regarding their effects on diabetic nephropathy and provide an overview of the potential of polyphenols.

The circulating renin–angiotensin system (RAS) is an endocrine system with key functions in maintaining blood pressure, fluid volume, and electrolytes. The RAS in the kidney (intrarenal RAS) plays a critical role in the onset and progression of kidney diseases. However, the mechanism underlying the onset and progression of diabetic nephropathy in relation to the expression and secretion of angiotensinogen (AGT) in the kidneys remains unclear. In this review, we present an overview of the intrarenal RAS and its role in diabetic nephropathy, as well as reviewing the evidence for the use of urinary AGT as a biomarker of this system in diabetic nephropathy. We also describe the roles of isoflavones in the context of diabetic nephropathy. The considered studies show that the intrarenal RAS—especially AGT—plays a diversified role in diabetic nephropathy; for instance, the increase in AGT due to oxidative stress is suppressed by polyphenols with antioxidant capacity, which is thought to affect the progression of diabetic nephropathy. Therefore, clarification of how polyphenols affect the onset and progression of diabetic nephropathy may provide insights into new treatments for this illness.