This prospective study showed that abdominal artery calcification was common in PD patients. Older age, longer PD duration, diabetes, and previous CVD were correlated with AACS in prevalent PD patients. Furthermore, high AACS was an independent predictor of subsequent cardio-cerebral vascular disease and all-cause mortality in the study cohort.
Abdominal artery calcification is particularly common in dialysis patients, with the overall prevalence ranging from one third to more than 80 percent[4, 14–16]. We reported an abdominal artery calcification prevalence of 57.2% in our PD patients, in correspondence with published meta results in Asia population[4]. There were a few cross-sectional studies suggesting that abdominal artery calcification might be less common in PD patients compared to HD patients[14], while other studies reported no advantage of one modality over the other[4, 17].
Vascular calcification is a sophisticated process and our results suggest both demographics and comorbidity might contribute to its development. Age is a traditional risk factor for vascular calcification [16, 18, 19]. With body aging, pathologies promoting calcium deposits such as lipid deposition and decrement of smooth muscle and elastin might occur in vessel walls [18],[20]. Prolonged exposure to uremic toxins and biocompatible dialysate could lead to sustained activation of calcification inducers along with the down-regulation of calcification inhibitors [21, 22]. It has been shown that the prevalence of vascular calcification in incident PD patients increases from 47–56% after 1 year on dialysis[23]. Diabetes closely associated with vascular calcification, and insulin resistance, oxidative stress, and hyperglycemia are possible mechanisms participating in [24, 25]. In consist with several other studies, a previous history of CVD was found to be associated with higher AACS [16, 19]. No relationship was found between phosphate, PTH and calcium and abdominal artery calcification in the present study, which were reported as accelerators of calcification in some observational studies[26, 27]. The lack of association may relate to the time-dependent high variability of these biochemical makers since our analysis only included the parameters measured at the enrollment.
Imaging examinations to investigate vascular calcification include CT scan, abdominal plain X-ray, mammography and vascular ultrasound[5–7]. The optimum diagnostic technique for vascular calcification remains unsettled. CT based imaging is outstanding in accuracy and reproducibility, yet plain radiography is a convenient and inexpensive alternative, and it delivers substantially lower radiation[28]. The predictive value of AACS based on lateral lumbar X-ray film for CVD and mortality has been validated in the general population[29, 30]. Moreover, it has been shown that AACS correlates with coronary artery calcification score by electron beam CT in HD population[31].
Previous studies had provided evidence of abdominal artery calcification as a prognostic factor in ESRD patients. The Calcification Outcome in Renal Disease (CORD) Study, a large prospective study conducted in 47 European dialysis centers, explored the relationship between AACS and all-cause mortality as well as nonfatal cardiovascular events in a cohort of 1084 dialysis patients, of which the vast majority were on HD. The investigators found AACS to be an independent predictor of the adverse outcomes[9]. A few studies focused on PD populations and found that abdominal artery calcification is a risk factor of both mortality and CVD occurrence, but were carried in a rather small population or with restricted age-bracket[32, 33]. This relatively larger cohort study with longer follow-up periods might help for the extrapolation of these findings in PD population. Recently, Mäkelä S et al reported that severe arterial calcification (AACS ≥ 7) rather than moderate calcification (1≤AACS<7) was associated with adverse outcomes in Finnish PD patients[34]. Comparatively, out study found that even mild calcification (AACS≤4) can double the risk of MACCE and death compared to the ones without abdominal artery calcification, and regular screening of abdominal artery calcification to identify PD patients with excess CVD risks are therefore suggested.
Therapeutic interventions to prevent the progression of vascular calcification may be of great value in these patients identified with high AACS, which requires the long-term implementation of systematic interventions targeting at multiple pathogenic components[8, 35]. Control of mineral metabolism was considered critical to reducing the vascular calcification progression, and non-calcium-based phosphate binders and/or 1.25 mmol/L calcium dialysate are suggested. Compared with 1.75 mmol/L calcium dialysate, utilization of 1.25 mmol/L calcium dialysate tended to decrease serum calcium level without inducing high turn-over bone lesion in PD patients[36, 37]. A meta-analysis reported that in CKD stage 3-5D patients, Agatston scores were significantly lower in patients treated with non-calcium-based phosphate binders than those on calcium-based binders, with a mean score difference of -95.26 (95%CI − 146.68 to − 43.84)[38]. Excessive use of activated vitamin D should be avoided in patients with severe vascular calcification, and parathyroidectomy is recommended for severe secondary hyperparathyroidism[35]. Limited evidence implied that no beneficial effect of cinacalcet treatment on arterial stiffness despite the remarkable lowering of the PTH level in PD patients[39, 40], and clearly further randomized controlled trials with better design are needed.
CVD is highly prevalent in ESRD patients and is the leading cause of death in dialysis patients that accounts for more than 50% of all-cause mortality[9]. The presence and extent of arterial calcification are regarded as one of the major determinants for CVD morbidity and mortality through multifaceted pathogenesis. In CKD population, arterial calcification is characterized by lesions that occur in the medial vascular wall, which exacerbates arterial stiffness termed as arteriosclerosis[41]. Arterial rigidity is measurable through pulse wave velocity (PWV). Numerous studies in CKD and ESRD patients have reported this positive correlation between increased arterial calcification and faster PWV[42]. It is responsible for escalated systolic blood pressure, decreased diastolic blood pressure, and widened pulsatile pressure[43]. Increased wave reflections and high pulse pressure are independent risk factors for mortality [44]. Elevated systolic pressure aggravates ventricle afterload and oxygen consumption, leads to left ventricular hypertrophy, and results in myocardial fibrosis, arrhythmias and congestive heart failure,[45]. 1 g/m2.7/month increase in left ventricular mass index was associated with a 62% increase in the incident risk of cardiovascular events in HD patients[46]. Decreased diastolic pressure limits coronary perfusion and promotes myocardial ischemia, which in turn urges myocardial infarction and lethal arrhythmias[47].
Coronary artery calcification (CAC) is the traditional marker for coronary atherosclerotic burden and direct causal factor in the pathogenesis of ischemic heart diseases[48]. There is an observed association between aortic stiffness and CAC[49]. The stiff arterial wall may be subjected to greater shear and intraluminal stresses as the result of increased pulsatile pressure, inducing vessel wall damage and endothelial cell dysfunction which are the crucial steps of coronary atherosclerosis [50].
There are several limitations in our study. First, the single-center study design limits the generalizability of our results. Second, as mentioned above we only included laboratory parameters and AACS at the baseline of the study. The lack of serial assessments leads to inevitable confounders. The presence of the longitudinal changes in the time-dependent variables may provide more solid information.