Despite multiple therapeutic options, the incidence of diabetic nephropathy remains worrisome. Time has therefore come to undertake a new approach based on some breakthrough not only in medical biology but also in structural biology, chemistry, pharmacology and even computer science. Recent investigations have tried to translate several target molecules or factors identified by basic researches into clinical medicine, as delineated in this. Classical factors contributing to the pathology of diabetic nephropathy, e.g., hypertension, hyperglycemia, hyperinsulinemia, and hyperlipidemia, are now amenable to treatment. Current therapies however do not fully prevent its renal complications. Recent studies, mainly performed in experimental animals, have identified newer culprits in the pathogenesis, such as hypoxia, advanced glycation, oxidative stress, and other bioactive molecules. Animal experiments highlight the fact that reno-protection is not necessarily linked to hemodymanic (blood pressure) or metabolic (glycemic and lipid controls) alterations but appears rather associated with an improved hypoxia, oxidative stress, and/or advanced glycation. To assess the respective contribution of each of these mediators, small molecular weight compounds were designed to interfere with each factor or target molecule. It is indeed important to acquire tools to evaluate and confirm our hypotheses and to translate experimental results into clinical practice. Copyright by Medycyna Praktyczna. Krakbw 2009.
- Advanced glycation
- Oxidative stress
- Plasminogen activator inhibitor-1 (PAI-1)