Cigarette smoking as a risk factor for atherosclerosis and renal disease: novel pathogenic insights

Cigarette smoking is the major cause of preventable morbidity and mortality in the United States. It is a major risk factor for atherosclerotic vascular disease and recently was identified as an important risk factor in the progression of chronic kidney disease. Several compounds in cigarette smoke, including nicotine and reactive aldehydes (eg, acrolein), have been implicated as mediators of endothelial dysfunction and atherosclerosis in smokers. In addition, studies have demonstrated that nicotine induces endothelial dysfunction in humans and accelerates atherosclerosis in animals. Large clinical trials have suggested that cigarette smoking is a risk factor for progression of chronic kidney disease in diabetics and nondiabetics, and in polycystic kidney disease, lupus nephritis, and IgA nephropathy. Recent studies suggest that nicotine has powerful mitogenic effects and induces extracellular matrix production in human mesangial cells via reactive oxygen species generation. These effects of nicotine may play a major role in the pathogenic mechanisms that mediate the deleterious effects of smoking in renal disease.