Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: Cause or association?
ABSTRACT Chronic kidney disease (CKD) is strongly associated with cardiovascular disease (CVD); a graded inverse relationship between estimated glomerular filtration rate (eGFR) and cardiovascular event rates has emerged from large-scale observational studies. Chronic kidney disease is also associated with endothelial dysfunction (ED) although the precise relationship with GFR and the "threshold" at which ED begins are contentious. Abnormal endothelial function is certainly present in late-stage CKD but data in early-stage CKD appear confounded by disease states such as diabetes and hypertension which themselves promote ED. Thus, the direct effect of a reduction in GFR on endothelial function and, therefore, cardiovascular (CV) risk is far from completely established. In human studies, the precise duration of kidney impairment is seldom known and the onset of CVD often insidious, making it difficult to determine exactly when CVD first appears in the context of CKD. Kidney donors provide a near-ideal experimental model of CKD; subjects undergo an acute change from normal to modestly impaired renal function at the time of nephrectomy and lack the confounding co-morbidity that has made observational studies of CKD patients so challenging to interpret. By examining changes in endothelial function in living kidney donors before and after nephrectomy, useful insight might be gained into the pathophysiology of CVD in CKD and help determine whether targeting ED or the renal disease itself has the potential to reduce CV risk.
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ABSTRACT: BACKGROUND: Pneumoperitoneum during laparoscopic surgery is known to affect visceral blood flow and result in oxidative stress. Whether epidural anesthesia will effectively reduce visceral ischemia and oxidative stress by blocking the sympathetic nervous system (SNS) during laparoscopic surgery has not been proven. METHODS: Forty-five patients who were to undergo robot-assisted laparoscopic prostatectomy were randomly assigned to the combined general-epidural anesthesia group (group GE, n = 22) or to the general anesthesia group (group G, n = 23). Blood pressure, heart rate, and the balance between sympathetic and parasympathetic nervous system activity as measured by heart rate variability were recorded at 10 min after induction of anesthesia (T1), 60 (T2) and 120 (T3) min after intra-abdominal CO(2) insufflation, and 10 min after returning the patient to the supine position following CO(2) exsufflation (T4). Arterial blood gas analysis and blood sampling for measurements of nitrite (NO(2-)) and malondialdehyde (MDA) were performed at all time points. RESULTS: Intraoperative mean blood pressure was significantly lower in group GE compared with group G. The low-frequency to high-frequency ratio was significantly increased after induction of pneumoperitoneum in group G but was unchanged in group GE. Plasma levels of nitrite decreased after pneumoperitoneum induction in group G while there was no change in group GE. A significant increase in MDA levels was seen in group G after pneumoperitoneum induction and were higher than group GE at T3 and T4. The 24-h urine output was higher in group GE than in group G on POD 1. The 24-h CrCl was higher in group GE on POD 1 but was not different between groups on POD 2. CONCLUSIONS: Combined epidural and general anesthesia effectively blocks SNS stimulation during laparoscopic surgery and reduces NO inactivation and oxidative stress.Surgical Endoscopy 10/2012; 27(3). DOI:10.1007/s00464-012-2536-5 · 3.31 Impact Factor
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ABSTRACT: End stage renal disease is associated with a very high risk of premature cardiovascular death and morbidity. Early stage chronic kidney disease (CKD) is also associated with an increased frequency of cardiovascular events and is a common but poorly recognised and undertreated risk factor. Cardiovascular disease in CKD can be attributed to two distinct but overlapping pathological processes, namely atherosclerosis and arteriosclerosis. While the risk of athero-thrombotic events such as myocardial infarction is elevated, arteriosclerosis is the predominant pathophysiological process involving fibrosis and thickening of the medial arterial layer. This results in increased arterial stiffness causing left ventricular hypertrophy and fibrosis and the exposure of vulnerable vascular beds such as the brain and kidney to high pressure fluctuations causing small vessel disease. These pathophysiological features are manifest by a high risk of lethal arrhythmia, congestive heart failure, myocardial infarction and stroke. Recent work has highlighted the importance of aldosterone and disordered bone mineral metabolism.Heart (British Cardiac Society) 10/2012; 99(6). DOI:10.1136/heartjnl-2012-302818 · 6.02 Impact Factor
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ABSTRACT: Patients with end-stage renal disease are characterized by extensive vascular calcification and high cardiovascular disease (CVD) risk. Calcification in end-stage renal disease patients represents at least two distinct pathologic processes. Calcification within the tunica intima frequently is associated with lipid-laden, flow-limiting atherosclerotic plaques. These appear as spotty areas of calcification interspersed with noncalcified arterial segments on plain radiography and generally are found near arterial branch points in medium-sized conduit arteries. In contrast, medial arterial calcification (MAC) involves deeper layers of the arterial wall; tends to affect the artery diffusely, appearing as a linear contiguous tram-track pattern of calcification on plain radiography; and often involves smaller muscular arteries such as the radial artery, intermammary arteries, and arteries in the ankle and foot. Both are related to CVD events, but potentially through different mechanisms. Atherosclerotic calcification may be marking the total burden of atherosclerosis, whereas MAC may lead to arterial stiffness and left ventricular hypertrophy. Existing data suggest that altered mineral metabolism may promote MAC, whereas heightened inflammation and oxidative stress contribute to atherosclerosis. Dysregulation of normal anticalcification factors and elastin degradation are common to both processes. Risk of vascular calcification also may be increased by the use of certain medications in the setting of chronic kidney disease. This review compares and contrasts known risk factors for MAC and atherosclerosis, describes existing and emerging technologies to distinguish between them, and reviews the existing literature linking each with CVD events in dialysis patients and in other settings.Seminars in Nephrology 03/2013; 33(2):93-105. DOI:10.1016/j.semnephrol.2012.12.011 · 2.94 Impact Factor