Inflammatory Targets in Diabetic Nephropathy

Abstract

One of the most frequent complications in patients with diabetes mellitus is diabetic nephropathy (DN). At present, it constitutes the first cause of end stage renal disease, and the main cause of cardiovascular morbidity and mortality in these patients. Therefore, it is clear that new strategies are required to delay the development and the progression of this pathology. This new approach should look beyond the control of traditional risk factors such as hyperglycemia and hypertension. Currently, inflammation has been recognized as one of the underlying processes involved in the development and progression of kidney disease in the diabetic population. Understanding the cascade of signals and mechanisms that trigger this maladaptive immune response, which eventually leads to the development of DN, is crucial. This knowledge will allow the identification of new targets and facilitate the design of innovative therapeutic strategies. In this review, we focus on the pathogenesis of proinflammatory molecules and mechanisms related to the development and progression of DN, and discuss the potential utility of new strategies based on agents that target inflammation.

Keywords: diabetes; inflammation; renal disease.

Figure 1

Overview of the participation of inflammatory mechanisms in the pathophysiology of diabetic nephropathy. In the diabetic milieu, glucose, advanced glycation end products (AGEs), angiotensin II, and oxidative stress activate a variety of signaling cascades leading the production of chemokines and cytokines that drive monocyte infiltration and the development of inflammation. AGE, advanced glycation end product; nuclear transcription factor kappa B (NFκB); JAK-STAT, Janus kinase/signal transducer and activator of transcription; Nrf2, nuclear factor-2 erythroid related factor 2; VCAM1, vascular cell adhesion molecule 1; ICAM1, intercellular adhesion molecule; TGF-β, transforming growth factor beta; TNF, tumor necrosis factor alpha; IL, interleukin.