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? In older men, plasma concentration of cystatin C, probably as a marker of mild renal disease, is a strong independent predictor of both vascular and nonvascular mortality. Death rates amongst people with chronic kidney disease requiring dialysis are about 10 to 100 times greater than those in the general population, with much of this excess mortality being from vascular causes [1]. Chronic kidney disease (CKD) [defined as an estimated glomerular filtration rate (eGFR) of http://www.selleckchem.com/products/avelestat-azd9668.html that people with CKD have 30% to 80% higher risks http://www.selleckchem.com/products/a-1331852.html of all-cause mortality [3�C6]. Whilst the absolute risk of death increases exponentially with decreasing renal function, there is considerable uncertainty about the shape and strength of any associations of mild-to-moderate renal impairment with vascular and nonvascular mortality. In particular, it is unclear if the risks of vascular disease increase only when renal function drops below a certain threshold. Some of the uncertainties about the shape and strength of the associations of renal function with vascular diseases relate to an insufficient number of events examined in previous studies, variable inclusion of people with prior vascular disease at enrolment, incomplete adjustment for other risk factors and the insensitivity of creatinine as a marker of renal function in people with normal or mildly impaired renal function [7�C10]. Since renal function declines with age and the absolute risks of death and disease increase with age, there is a need to assess the relevance of mild-to-moderate reductions in renal function for cause-specific mortality in older people. Such an assessment should take account of known cardiovascular risk factors (including lifetime blood pressure) and avoid reliance on creatinine-based estimates of GFR. Cystatin C, a nonglycosylated basic http://www.selleck.cn/products/PLX-4720.html protein produced at a constant rate by all nucleated cells, has been proposed as a more sensitive marker of renal function than creatinine and particularly in the setting of mild renal impairment [10�C12]. Cystatin C is filtered by the renal glomerulus and metabolized by the proximal tubule. In contrast with creatinine, blood cystatin C concentrations appear to be much less affected by age, sex or muscle mass. The aims of this study were to assess the shape and strength of the associations of cystatin C with vascular and nonvascular mortality, after taking account of prior disease and other risk factors, in a prospective cohort study of 5371 older men followed for an average of 11?years. Between 1967 and 1970, 19?019 male civil servants aged 40�C69?years working in London were recruited into the Whitehall study [13, 14].