Lipid oxidative stress and the anti-inflammatory properties of statins and ACE inhibitors

Observational studies in different populations indicate a positive relationship between dyslipidemia, cardiovascular events, and kidney disease progression. Patients with chronic renal diseases usually present with conditions (inflammation, oxidative stress) that can induce quantitative and qualitative changes in lipoprotein composition, making these particles more atherogenic. Several large randomized trials have shown that lowering cholesterol with statins reduces coronary mortality and morbidity across a wide range of cholesterol levels. Moreover, statins ameliorated renal function and structure in experimental models of progressive renal disease as well as in patients with proteinuric disease. It has been hypothesized that statins may directly modulate intracellular signaling systems involved in cellular proliferation, inflammatory, and fibrogenic responses. In addition, studies in animals have shown that the mevalonate pathway also may be involved in the regulation of the renin-angiotensin system, providing the rationale for the use of statins in combination with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor antagonists, 2 classes of drugs that have evidenced beneficial effects in different forms of renal diseases. Preliminary studies have shown that a multidrug approach may induce remission of proteinuria, lessen renal injury, and protect from loss of function in those patients whose condition does not fully respond to a single treatment.