Oxidative Stress, Lipoproteins and Angiotensin II— The Unholy Triade in the Pathogenesis of Renal Fibrosis

Renal fibrosis usually indicates irreversible tissue damage, irrespective of the initial cause. Thus, it is most relevant to understand mechanisms leading to renal fibrosis. Oxidative stress has emerged as an important factor contributing to tissue damage, and oxidative stress is enhanced in a variety of inflammatory disease states relevant for the kidney. It is therefore the purpose of this Chapter to discuss the role of oxidative stress in the development of renal fibrosis. Inflammation is generally associated with enhanced oxidative stress, and since multiple factors contribute to inflammation [such as cytokines (e.g., interleukin-6, tumor necrosis factor α), infection, ischemia reperfusion injury, homocysteine, advanced glycation end products, atherogenic lipoproteins, or angiotensin II], multiple factors can cause enhanced oxidative stress. Here we will focus on the role of atherogenic lipoproteins, particularly oxidized low density lipoproteins, and the activated renin angiotensin system, for several reasons: firstly, these factors are well characterized as proinflammatory and as stimulators of superoxide-generating enzymes; secondly, the contribution of these factors to tubulointerstital fibrosis has frequently been described; and thirdly, we already possess pharmacological tools to efficiently lower their activity. Thus, this Chapter highlights the interplay of oxidative stress, atherogenic lipoproteins, and the renin angiotensin system in the pathophysiology of renal fibrosis and discusses potential treatment options.