Cross-Talk between the Kidney and the Cardiovascular System

Abstract

In recent years, increasing evidence has been provided that even minor renal dysfunction is a powerful cardiovascular risk factor that induces typical cardiovascular alterations and thus predisposes to coronary heart disease as well as to noncoronary cardiovascular problems. This first had been noted in patients with diabetes but now has been confirmed amply in patients without diabetes as well. Numerous heterogeneous abnormalities have been described in patients with early renal dysfunction (e.g., microalbuminuria, reduced estimated GFR). One final common pathway seems to be endothelial cell dysfunction. The link between albuminuria and generalized endothelial cell dysfunction (as indicated by diminished flow-mediated vasodilation, markers of endothelial cell dysfunction, sloughed off endothelial cells, and high transcapillary albumin escape rate) is unclear. In patients with early renal dysfunction, a long list of classical and nonclassical cardiovascular risk factors have been identified: Elevated asymmetric dimethyl-L-arginine concentrations, markers of microinflammation, oxidative stress, features of metabolic syndrome, abnormal adipokine concentrations, dyslipidemia, inappropriate activation of the renin-angiotensin system, and sympathetic overactivity. The mechanisms that link dysfunction of the kidney and the cardiovascular system are being sought. The most interesting unifying concept, however, is deranged fetal programming linking nephron underdosing to the increased cardiovascular risk.

Asymmetric Dimethylarginine and Clinical Outcomes in Chronic Kidney Disease

“…Furthermore, in CKD patients, cardiovascular disease is the major cause of death, which cannot be entirely explained by the clustering of the traditional cardiovascular risk factors (3). It has been hypothesized that this excessive risk can be attributed, at least in part, to endothelial dysfunction and reduced bioavailability of nitric oxide (NO), which might play a pivotal role in the initiation and progression of atherosclerosis and might be a potential link between cardiovascular disease and CKD (4). In addition, endothelial dysfunction assessed by acetylcholine-stimulated vasodilation has been shown to be associated with the decline of renal function in hypertensive patients (5).…”

Smoking

“…A tight relationship between CKD and CVD has become apparent: On the one hand, CKD and its epiphenomena increase the risk for CVD (8); on the other hand, CVD accounts for the majority of morbidity and mortality in patients with CKD (6,9). Diabetes and hypertension are widely acknowledged risk factors for kidney damage, and data increasingly indicate that smoking can have a negative effect on the kidney (for review, see references [10 -12]).…”

High White Blood Cell Count and Low Estimated Glomerular Filtration Rate Are Independently Associated With Serum Level of Monocyte Chemoattractant Protein‐1 in a General Population

“…atherosclerotic heart disease, 18,19 our present observations suggest that elevation of MCP-1 levels could link to CKD to the increased risk of CVD in a general population. The present study did not clarify how decreased eGFR levels were independently correlated with serum MCP-1 levels.…”

“…17 Recent clinical observations have shown that even minor renal dysfunction is associated with the increased risk of future cardiovascular events in a general population. 18,19 Now chronic kidney disease (CKD) is one of the risk factors of cardiovascular disease (CVD) in humans, and the concept of so-called cardiorenal syndrome has received much attention. 20 -22 Although several possible mechanisms that could link to CKD to CVD have been proposed so far, 23,24 given the proatherosclerotic properties of MCP-1, it is conceivable that MCP-1 may contribute to the increased risk of CVD in CKD patients.…”