The present multicentre, cross-sectional study comprised 933 patients with dialysis-dependent CKD. AAC was investigated using plain lateral radiographs, which are widely available, easy to use, relatively inexpensive and involve low exposure to radiation. To our knowledge, this is the largest radiological documentation of arterial calcification in dialysis patients. The main findings were severe premature calcification of the abdominal aorta that was related to age, duration of dialysis and history of cardiovascular disease. Aortic calcification was most severe in front of the fourth lumbar segment and decreased towards the higher lumbar levels. Only one in five patients had no visible calcification in the abdominal aorta, whereas >50% had calcification in all four segments, indicating severe calcification.
Several radiological methods, such as EBCT, multislice spiral CT and plain radiographs, have been used to investigate aortic calcification [16,17
]. Such methods are costly and are primarily used for clinical research purposes in nephrology. A few studies have systematically investigated plain radiographs as a means of assessing calcification in dialysis patients [18,19
]. None of these methods have been accepted as a gold standard in cardiovascular risk assessment (reviewed in [20
]). The current study investigated X-rays of the abdominal aorta. In Belgium and the Netherlands, a special goal was to include up to 50% of peripheral hospitals. Without the more specific equipment available in university centres, a simple lateral lumbar X-ray affords them an easy inexpensive method for the initial screening of cardiovascular risk in their patients. The scoring system applied is a validated method developed on the basis of lateral lumbar X-rays from the general population in the Framingham heart study [10
], where it was proven to be predictive for cardiovascular risk and outcome [11,12
]. The baseline prevalence of calcification in that cohort, which had a mean age of 54 years, was 37% in men and 27% in women and increased significantly during the 25 years of follow-up. Kiel et al
] investigated 554 subjects using the same methodology and observed that, over a period of 25 years, AAC increased sixfold in men and eightfold in women in whom the change correlated to the degree of bone loss.
Several studies suggest that aortic calcification correlates with the findings in coronary arteries, which in turn predict all-cause mortality [5
]. In line with these studies are the findings that the severity of AAC is also an important indicator of cardiovascular disease and mortality. Calcification scored using the same system as in the present study was strongly related to the development of congestive heart failure, coronary heart disease and cardiovascular events in the general population [11,12
]. AAC remained as an independent predictor of risk even after the adjustment for traditional cardiovascular risk factors such as diabetes, older age, male gender, family history of coronary heart disease, systolic blood pressure, left ventricular hypertrophy, smoking, dyslipidaemia and body mass index [11
]. In the present study, a history of cardiovascular events was associated with 224% increased odds of calcification. Interestingly, Okuno and co-workers reported recently on a cohort of 515 haemodialysis patients showing that the presence of AAC was significantly associated with both all-cause and cardiovascular mortality during a mean follow-up of 51 months [14
There was a significant age-related increase in AAC in the present study, a finding that has previously been shown in both non-renal [10
] and renal [23
] patients. In the general population, calcific deposits in the posterior aortic wall have been shown to occur most commonly at the level of L4 and in the anterior wall at levels L3 and L4 [24
]. In the present study of ESRD patients, the most pronounced calcification was also detected at level L4, suggesting that the distribution of AAC is similar, but more extensive and premature in ESRD.
Although some reports on the general population [22
] have suggested that men are particularly prone to calcification, no significant sex-related difference was observed in the present study. The duration of dialysis correlates with calcification in the coronary [23
], carotid and peripheral arteries [8
], but the association is less clear in the thoracic aorta [23
]. In the present study, there was a significant relation between dialysis vintage and AAC: each year on dialysis increased the odds for AAC ≥1 by 11%. However, pulse pressure did not predict AAC scores, which is in line with the recent study by Bellasi and co-workers [13
], where no association was found between pulse pressure and coronary artery calcification.
In the CORD study, 19% of patients had no visible calcification in their abdominal aorta, even though some of them were >80 years of age. These findings are in line with certain previous observations [2
], and it has been suggested that these individuals rarely develop calcification at follow-up [2
]. However, in a recent longitudinal study, Asmus et al.
] followed 72 haemodialysis patients, of whom 41 used calcium-containing phosphate binders and 31 used sevelamer hydrochloride. A subset of these patients (15%) had no coronary or thoracic aortic calcification at baseline, but their calcification developed during 2 years of observation and was most prevalent in those receiving calcium-containing binders. Thus, it remains to be proven if the ‘non-calcified’ patients have some typical biochemical and/or genetic features that protect them from calcification. The analysis of the aortic X-rays at the 24-month follow-up of the CORD study will provide further insight into this question.
The present cross-sectional study has some limitations. The increased vascular calcification and its relationship to age and dialysis vintage are well known. In a recent study [13
] on 140 prevalent haemodialysis patients with a mean age of 55 years and dialysis vintage of 2.7 years, the mean AAC was 4.4, i.e. much lower than that in the present study on North European patients. Importantly, patients with severely reduced life expectancy were excluded. Furthermore, only those patients in whom parameters of arterial stiffness by applanation tonometry could be recorded were included; this measure was impossible in some patients with severe vascular disease and/or atrial fibrillation. Most likely this resulted in a favourable selection bias and the actual calcification burden of dialysis patients may be even more profound.
In conclusion, severe calcification of the abdominal aorta as detected by lateral lumbar radiography was found in this large cohort of dialysis patients from Northern Europe. The pattern of distribution was similar to previously reported findings in the general population in the Framingham heart study, with the most severe lesions detected at the L4 level decreasing towards L1. Importantly, a subset (19%) of dialysis patients had no evidence of calcification whereas the majority had extensive calcification involving the entire length of the abdominal aorta. Since AAC correlates with calcification at other sites (e.g. coronary arteries) and has been shown to have significant prognostic significance for cardiovascular events and mortality, this easy and inexpensive method may prove to be a useful alternative for CT-based techniques in epidemiological studies in patients with CKD. Furthermore, it may serve as a part of the cardiovascular risk assessment and as a guide to more sophisticated examinations as recently recommended by an international expert group [28
]. The ongoing CORD study will provide valuable information about the relationships between AAC, arterial compliance, their evolution during dialysis or after transplantation and their prognostic significance.