M ild to moderate renal insufficiency now has emerged fully as a major public health problem. Population-based studies (1) and secondary analyses of intervention studies in hypertensive patients (2) and in selected patients at high cardiovascular risk (3) have shown coherently that classical risk factors such as hypertension, diabetes, hyperlipidemia, smoking, and overweight/obesity represent major correlates of renal dysfunction. Although its importance for prevention is still debated, convincing evidence was provided recently that low-grade inflammation, as measured by highly-sensitivity C-reactive protein (CRP), is an early marker of renal dysfunction and of cardiovascular events in the general population (4) and a risk factor for cardiovascular complications and progressive renal insufficiency in patients with chronic kidney disease (CKD) (5). We recently reported an association between mild to moderate renal impairment and the hemodynamic response to acetylcholine (ACh), an established test of endothelial function, in a large group of nevertreated individuals with uncomplicated essential hypertension (6). A corollary finding in this study was that renal function also was associated with serum CRP, suggesting that inflammation may be a critical factor mediating endothelial dysfunction and renal insufficiency in individuals with essential hypertension. Although merely associative, these observations in a carefully selected population of hypertensive individuals are important in that they may be hypothesis generating for understanding the high risk associated with mild to moderate renal insufficiency.In this study, we therefore performed a secondary analysis in the same database to test the influence of inflammation, as measured by serum CRP, on the association between altered hemodynamic response to ACh and mild to moderate renal insufficiency in individuals with essential hypertension. This analysis, based on multivariate modeling, suggests that inflammation is a critical factor in the chain of events that lead to renal dysfunction in hypertensive individuals.