Coronary artery calcifications in children and young adults treated with renal replacement therapy

Editor's note Please see also Editorial comment by I. B. Salusky and W. G. Goodman, pp. 1738–1742. Sir, Cardiovascular disease (CVD) and death from cardiac causes, especially from myocardial infarction, is a major threat to patients treated with renal replacement therapy (RRT) both during the period of dialysis and after renal transplantation [1,2]. It therefore seems of great clinical importance to identify patients at high risk for CVD as early as possible. Coronary artery calcifications (CAC) are associated with all histological stages of atherosclerosis and are strongly associated with clinical symptoms of CVD. Recently, electron beam computed tomography (EBCT) has been introduced as a new noninvasive, cost‐saving technique for the detection of CAC. With this method, minute amounts of calcium can be detected, localized and quantified within a very short time. Recent clinical studies have demonstrated that the amount of coronary artery calcium is related to histological plaque area and to overall plaque volume [3]. CAC detected by EBCT in symptomatic as well as asymptomatic adult patients are associated with an elevated cardiovascular morbidity and mortality. Moreover, the absence of calcific deposits on EBCT scan implies the absence of significant angiographic coronary narrowing [4,5]. In a recent study adult haemodialysis patients (mean age 55 years) had a remarkably high incidence of CAC, as well as mitral and aortic valve calcifications [6]. We sought the presence of CAC by EBCT in asymptomatic children and young adults treated with RRT and retrospectively reviewed their medical records for the presence of classical risk factors for atherosclerosis as well as evidence of severe hyperparathyroidism. Participation was voluntary. There was no control group in this study, but it can be assumed that the normal CAC score in this age group is 0 [7]. Since 1997 we studied a total of 16 children and young adults aged 14–39 years (median 26.5 years, seven female and nine male) treated with RRT. The duration of RRT treatment ranged from 2.5 to 21 years (Table 1). All patients were studied by EBCT and three patients (patients KC, SC, DM) underwent exercise thallium scintigraphy. Coronary foci with a CT density of 130 Hounsfield units and an area of 4 adjacent pixels (1.03 mm2) were determined to represent coronary artery calcium. In the presence of EBCT coronary calcification, a lesion score was calculated by multiplying the area of the hyperattenuating focus (130–199 HE=1, 200–299 HE=2, 300–399 HE=3, >400 HE=4). The mean calcium score was determined as the sum of all lesion scores. Fifteen coronary segments were classified according to the suggestion of the American Heart Association [5]. The EBCT‐scan was abnormal in a total of six patients. CAC were demonstrated in four cases in the right coronary artery, in four cases in the left circumflex artery and in another five cases in the left anterior descending artery. The abnormal CAC scores ranged from 1 to 807. The thallium scan was normal in three patients. Only one patient (patient KC) had a history of severe hyperparathyroidism; at the time of investigation, serum iPTH levels in our patients ranged from 3 to 313 ng/ml. It is of interest, that only one patient (SD) without CAC had therapy‐resistant, prolonged hypercalcaemia and hyperphosphataemia. In all other patients calcium and phosphate serum levels were adequately controlled by the administration of phosphate binding agents (Table 1). These data indicate that even adolescents and young adults treated with RRT may have significant coronary calcifications. Our study was uncontrolled and the percentage of patients with calcifications (37.5%) may not reflect the true prevalence of CVD in this population. However, cardiac death is the main cause of mortality in children and adolescents treated with RRT [8]. The absence of clinical symptoms in afflicted patients is in sharp contrast to the degree of calcification, since haemodynamically significant stenoses with more than 50% narrowing have been found associated with an EBCT score above 500. We conclude that severe but asymptomatic coronary calcifications may be present in a high percentage of young patients treated with RRT, even after successful renal transplantation. It is possible that this represents a specific form of vasculopathy and the development of calcification is accelerated in patients with ESRD resulting in a ‘uraemic’ atherosclerosis, characterized more by sclerosis and calcification than by atheroma. Early identification of young patients with a high risk for CVD should be an issue of high priority for prevention of CVD in patients with RRT; our study indicates that EBCT may be a suitable tool. aPlasma levels of calcium and phosphate; median of last 3 months. bTotal time of treatment with phosphate binding agents; alh=aluminiumhydroxide. aPlasma levels of calcium and phosphate; median of last 3 months. bTotal time of treatment with phosphate binding agents; alh=aluminiumhydroxide.