Bidirectional Nature of Cardiovascular and Kidney Disease

Cardiovascular disease (CVD) is the principal cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD promotes hypertension and dyslipidemia. Diabetes causes diabetic nephropathy, leading to the progression of renal failure. These traditional cardiovascular risk factors can promote CVD development. In addition, inflammatory mediators such as cytokines, chemokines, adhesion molecules, fibroblast growth factor 23, homocysteine, or reactive oxygen species are often elevated and the renin–angiotensin system, endothelin, and the sympathetic nervous system are frequently activated in patients with CKD, accelerating atherosclerosis and/or left ventricular hypertrophy. Mineral dysregulation accompanied by reduction of vitamin D, hyperphosphatemia, and hyperparathyroidism in CKD patients promotes vascular calcification associated with end-stage renal disease. Accelerated atherosclerosis then leads to increased prevalence of coronary artery disease, peripheral arterial disease, arterial stiffness, left ventricular hypertrophy, and cerebrovascular disease. On the other hand, renal dysfunction can result from diminished renal perfusion secondary to low cardiac output in left ventricular failure, peripheral arterial disease, and atherosclerosis and increased renal vasoconstriction mediated by neurohormonal and autonomic activation. Thus, traditional and non-traditional cardiovascular risk factors serve as cardiovascular and kidney risk factors. Consequently, kidney and cardiovascular dysfunction bidirectionally promote chronic renal failure and congestive heart failure. Whether differences in CVD in CKD patients suggest preventative or therapeutic strategies unique to this population remains unclear. Randomized controlled clinical trials must confirm the effectiveness of current pharmacological and interventional therapies modifying traditional and novel cardiovascular risk factors in patients at each stage of CKD, with or without unique co-morbidities.