Abstract
An epidemiological relationship between urolithiasis and cardiovascular diseases has extensively been reported. Endothelial dysfunction is an early pathogenic event in cardiovascular diseases and has been associated with oxidative stress and low chronic inflammation in hypertension, coronary heart disease, stroke or the vascular complications of diabetes and obesity. The aim of this study is to summarize the current knowledge about the pathogenic mechanisms of urolithiasis in relation to the development of endothelial dysfunction and cardiovascular morbidities. Methods: A non-systematic review has been performed mixing the terms “urolithiasis”, “kidney stone” or “nephrolithiasis” with “cardiovascular disease”, “myocardial infarction”, “stroke”, or “endothelial dysfunction”. Results: Patients with nephrolithiasis develop a higher incidence of cardiovascular disease with a relative risk estimated between 1.20 and 1.24 and also develop a higher vascular disease risk scores. Analyses of subgroups have rendered inconclusive results regarding gender or age. Endothelial dysfunction has also been strongly associated with urolithiasis in clinical studies, although no systemic serum markers of endothelial dysfunction, inflammation or oxidative stress could be clearly related. Analysis of urine composition of lithiasic patients also detected a higher expression of proteins related to cardiovascular disease. Experimental models of hyperoxaluria have also found elevation of serum endothelial dysfunction markers. Conclusions: Endothelial dysfunction has been strongly associated with urolithiasis and based on the experimental evidence, should be considered as an intermediate and changeable feature between urolithiasis and cardiovascular diseases. Oxidative stress, a key pathogenic factor in the development of endothelial dysfunction has been also pointed out as an important factor of lithogenesis. Special attention must be paid to cardiovascular morbidities associated with urolithiasis in order to take advantage of pleiotropic effects of statins, angiotensin receptor blockers and allopurinol.
Highlights
In another case control study that examined the impact of coronary heart disease (CHD) risk factors on calcium oxalate (CaOx) stone formation, it was concluded that CaOx formers are significantly associated with several CHD risk factors, including smoking habit, hypertension, hypercholesterolemia, and obesity [129]
Cardiovascular disorders have been independently associated to urolithiasis disorders and lithiasic patients present a higher incidence of cardiovascular diseases, myocardial infarction and stroke with relative risks between 1.20 and 1.24
Endothelial dysfunction is the preclinical stage of atherosclerosis and is highly associated with cardiovascular morbidities
Summary
Budgetimpact analyses based on 65 million population (France) have established the annual cost of urolithiasis in €590 million [1]. It has recently been suggested a significantly increased risk of kidney stone development secondary to diet factors and has been associated with pathologies such as obesity, metabolic syndrome or diabetes [2]. These alterations are associated with chronic kidney disease (CKD) and epidemiological data indicate that obesity is an independent risk factor for the development of chronic kidney injury [3]. The aim of this review is to summarize the current knowledge and the latest findings on the pathogenic mechanisms underlying endothelial dysfunction in urolithiasis, paying special attention to the role of the reactive oxygen species (ROS) as an underlying mechanism
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