We searched PubMed and Medline in April, 2012, with search terms that included but were not restricted to “chronic kidney disease”, “chronic kidney failure”, “glomerular filtration rate”, or “albuminuria”, in combination with “cardiovascular morbidity”, “cardiovascular mortality”, “cardiovascular risk”, “myocardial infarction”, or “heart failure”. Further publications were identified from references cited in relevant articles. We also relied on our own familiarity with the scientific
SeriesChronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention
Introduction
Bright1 wrote in 1836, “The obvious structural changes in the heart have consisted chiefly of hypertrophy...and what is most striking, out of fifty-two cases…no valvular disease could be detected in thirty-four…This naturally leads us to look for some less local cause”, and “It is observable, that the hypertrophy of the heart seems, in some degree, to have kept pace with the advance of disease in the kidneys; for in by far the majority of cases, when the heart was increased, the hardness and contraction of the kidney bespoke the probability of long continuance of the disease.” Bright was the first to report the association between chronic kidney disease and cardiovascular abnormalities. He suggested that the altered quality of the blood in patients with renal disease affected the peripheral vasculature, particularly the capillaries, in a way that required increased force to propel the blood around the body.2 By taking the view that renal disease is the primary disorder and cardiovascular changes are secondary, Bright established the concept of the renal origin of cardiovascular disease. Many studies have since confirmed and extended this association, and explanations have been sought. As part of this Series on global kidney disease, we discuss the relation between chronic kidney disease and cardiovascular risk. We present available information on the epidemiology, pathophysiological mechanisms, and prevention of chronic kidney disease and aim to provide guidance for future research.
Section snippets
Cardiovascular risk
As discussed by Eckardt and colleagues3 in this Series, chronic kidney disease is defined as impaired kidney function or raised proteinuria that are confirmed on two or more occasions at least 3 months apart. The estimated glomerular filtration rate is the recommended method of assessment. The preferred equation to calculate estimated glomerular filtration rate is that of the Chronic Kidney Disease Epidemiology Collaboration (commonly known as the CKD-EPI), which takes into account sex, age,
Pathophysiological mechanisms
Increased cardiovascular risk in individuals with chronic kidney disease is due partly to the high prevalence of traditional risk factors, such as hypertension and diabetes. The associations of kidney function and albuminuria with cardiovascular risk are, however, independent of these traditional cardiovascular risk factors. Thus, non-traditional kidney-specific mechanisms make notable contributions to cardiovascular risk. Elucidation of these mechanisms could reveal ways to lessen the
Prevention of cardiovascular disease
Cardiovascular disease can be prevented by lifestyle and pharmacological interventions. In low-income countries lifestyle modifications might be particularly useful. The prevention of cardiovascular disease in patients with chronic kidney disease is generally focused on achieving the best possible control of traditional cardiovascular risk factors (Table 1, Table 2). In view of the progressive increase in cardiovascular risk as kidney function declines, however, prevention of loss of kidney
Diagnosis and treatment of established cardiovascular disease
Patients with recognised symptoms of acute coronary syndromes are generally referred to hospital, where the diagnostic work-up routinely consists of electrocardiography, measurement of cardiac damage biomarkers, and, sometimes, coronary angiography. In cases of confirmed acute coronary syndrome, percutaneous thrombolysis or coronary artery bypass grafting are used, followed by medical treatment and lifestyle advice to prevent recurrence. Patients with chronic kidney disease are disadvantaged at
Future challenges and goals
Recommendations for prevention and treatment in patients with chronic kidney disease (Table 1, Table 2) are, unfortunately, based on only a small number of trials that have investigated cardiovascular disease specifically in populations of patients with chronic kidney disease. Most of these trials were underpowered to assess hard endpoints for clinical outcomes. Analyses of subpopulations of patients with chronic kidney disease in large cardiovascular randomised, controlled trials are sparse,
Conclusions
Since Bright's first description of the association between chronic kidney disease and cardiovascular disease, we have come a long way. Many epidemiological studies have confirmed this association and established that it is not only due to the fact that these two diseases share common risk factors, such as smoking, obesity, hypertension, hypercholesterolaemia, and diabetes. Mechanisms specific to chronic kidney disease promote vascular disease and, therefore, substantially increase the burden
Search strategy and selection criteria
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