Is atherosclerosis accelerated in young patients with end-stage renal disease? The contribution of paediatric nephrology.

The concept of an acceleration of atherosclerosis due to end-stage renal disease (ESRD) was first proposed by Lindner et al. [1] who observed a very high incidence of myocardial infarction in the Seattle haemodialysis population in 1974. Subsequent studies have confirmed a high prevalence of atherosclerotic lesions in dialysis patients by autopsy [2], by in vivo examination of iliac artery specimens [3] and by coronary angiography [3,4]. Approximately 50% of mortality in the dialysis population is due to cardiovascular disease (CVD) and the risk of death from CVD is elevated 30-fold for patients with ESRD compared with the general population [5]. Similarly, the incidence of CVD is much increased after renal transplantation [6]. The epidemic of CVD in ESRD may be explained by a unique accumulation of risk factors for atherosclerosis [7]. However, it has been widely debated whether the high mortality is due to an acceleration of atherosclerosis promoted by ESRD per se or to pre-existing co-morbidity from other causes. For both of these conflicting views there is evidence from retrospective as well as prospective studies [8–11]. Apart from these data, two lines of reasoning argue against the concept of accelerated classical atherosclerosis in ESRD. Firstly, many studies have not found any, or only a weak, correlation of cardiac death with hyperlipidaemia [12], even though the lipoprotein profile is clearly atherogenic in chronic renal failure, on dialysis and after transplantation [13,14]. This may be due to a number of reasons, including confounding factors (malnutrition associated with low cholesterol levels), strong effects of other non-traditional risk factors [Lp(a), inflammatory state] and oxidative modification of lipoproteins (not necessarily associated with an increase in lipoprotein particles) [15]. Nevertheless, this is in strong contrast to the fact that hyperlipidaemia has been shown to be a cardinal risk factor for atherosclerosis in the general population, characterized by a continuous and graded relationship with death from cardiac causes as well as total mortality [16–18]. Similarly, treatment of hyperlipidaemia is associated with a reduction in mortality from cardiac causes and overall mortality, but this has yet not been demonstrated in patients with ESRD. Secondly, mortality from cardiac causes in patients with ESRD in the US and in Europe is only partly due to ischaemic heart disease and myocardial infarction [19]. Although significant regional differences in contributing factors exist within Europe [20], the majority of deaths are associated with several other cardiac causes, such as arrhythmia, cardiomyopathy, cardiac arrest, pulmonary oedema and cardiac failure from other causes such as valvular heart disease. Therefore, although it is common to group these diagnoses as ‘cardiac causes’, this may actually confuse the issue; in the absence of carefully conducted mortality studies (including autopsy data), a diagnosis of arrhythmia could reflect coronary artery disease, but also other causes such as hyperkalaemia (diet errors, uncompliance, acidosis). Thus, only a fraction of ‘cardiac deaths’ may actually result from atherosclerosis. Therefore, it is obviously of interest to study this question in a young population without pre-existing multiple co-morbidities, i.e. young patients with ESRD occurring in childhood, who are now progressing into adulthood due to the accessibility of dialysis and transplantation at young age in Western countries [21].