Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention.

Chronic kidney disease1 (CKD) is a worldwide public health problem. In the United States, there is a rising incidence and prevalence of kidney failure, with poor outcomes and high cost. The number of individuals with kidney failure treated by dialysis and transplantation exceeded 320 000 in 1998 and is expected to surpass 650 000 by 2010.1,2 There is an even higher prevalence of earlier stages of CKD (Table 1).1,3 Kidney failure requiring treatment with dialysis or transplantation is the most visible outcome of CKD. However, cardiovascular disease (CVD) is also frequently associated with CKD, which is important because individuals with CKD are more likely to die of CVD than to develop kidney failure,4 CVD in CKD is treatable and potentially preventable, and CKD appears to be a risk factor for CVD. In 1998, the National Kidney Foundation (NKF) Task Force on Cardiovascular Disease in Chronic Renal Disease issued a report emphasizing the high risk of CVD in CKD.5 This report showed that there was a high prevalence of CVD in CKD and that mortality due to CVD was 10 to 30 times higher in dialysis patients than in the general population (Figure 1 and Table 2).6–18 The task force recommended that patients with CKD be considered in the “highest risk group” for subsequent CVD events and that treatment recommendations based on CVD risk stratification should take into account the highest-risk status of patients with CKD. The major goal of this statement is to review CKD as a risk factor for development of CVD. As background, we shall also review the definition of CKD and classification of stages of severity of CKD, the spectrum of CVD in CKD and differences from the general population, and risk factors for CVD in CKD. Definition and Classification of Stages of Severity and Types of CKD In 2002, the NKF published clinical practice guidelines on evaluation, classification, and risk stratification in CKD.3 In these guidelines, CKD is defined as either (1) kidney damage for 3 months, as confirmed by kidney biopsy or markers of kidney damage, with or without a decrease in glomerular filtration rate (GFR), or (2) GFR 60 mL · min 1 per 1.73 m for 3 months, with or without kidney damage (Table 1). Kidney damage is ascertained by either kidney biopsy or markers of kidney damage, such as proteinuria, abnormal urinary sediment, or abnormalities on imaging studies. The finding of proteinuria not only defines the presence of CKD but also has important implications for diagnosis of the type of kidney disease and is associated with a worse prognosis for both kidney disease progression and the development of CVD. Proteinuria is variously defined (Table 3).3,19–21 Measurement of albumin-to-creatinine ratio or total protein-tocreatinine ratio in untimed “spot” urine samples is recommended for assessment of proteinuria.3 GFR 60 mL · min 1 per 1.73 m is selected as the cutoff value for definition of CKD because it represents a reduction by more than half of the normal value of 125 mL · min 1 per 1.73 m in young men and women, and this level of GFR is associated with the onset of laboratory abnormalities characteristic of kidney failure, including increased prevalence and severity of several CVD risk factors. Estimation of GFR from serum creatinine and prediction equations including age, sex, race, and body size is recommended to avoid the