International Journal of Nephrology restricting the dose of calcium-based binders in patients with stage 5D CKD including those on PD, in the presence of persistent or recurrent hypercalcemia, arterial calciﬁcation, adynamic bone disease, and persistently low parathyroid hormone [75]. Vitamin D receptor activator (VDRA) has been the standard treatment for secondary hyperparathyroidism in patients with CKD. There is animal data to suggest that diﬀerent VDRAs have diﬀerential eﬀects on vascular calci- ﬁcation in uremia [40]. In the study by Mizobuchi et al., paricalcitol, a selective VDRA, showed no eﬀects on serum calcium, phosphorus and aortic calcium content in uremic animals in contrast to other VDRA such as calcitriol or doxercalciferol which increased serum calcium, phosphorus, and aortic calcium content. In addition, doxercalciferol treatment increased mRNA and protein expression of bone- related markers Runx2 and osteocalcin in the aorta, while paricalcitol did not [40]. Similar data suggest diﬀerential eﬀects of paricalcitol and calcitriol on aortic wall remodeling in uninephrectomized Apo-E knockout animals [76]. There are observational data to suggest that use of paricalcitol was associated with survival advantage over calcitriol in hemodialysis patients [77]. Randomized controlled trials will be required to determine whether paricalcitol may be associated with less progression of vascular calciﬁcation compared to other VDRA in the dialysis population. Cinacalcet hydrochloride is a calcimimetic agent that inhibits parathyroid hormone secretion from the parathy- roid cells by activation of the Ca receptor and emerges as a novel therapeutic agent for the treatment of secondary hyperparathyroidism in patients with CKD [78]. Previous double-blind randomized placebo-controlled trial showed that cinacalcet had comparable eﬃcacy in both hemodialysis and PD patients and eﬀectively reduced calcium, phospho- rus, and parathyroid hormone [79]. In the more recent 33-week ACHIEVE study that randomized hemodialysis patients to receive either cinacalcet and low-dose vitamin D analog or ﬂexible vitamin D analog, a more signiﬁcant reduction in parathyroid hormone (PTH) (median percent change, −47% versus −11%), calcium, and phosphorus was observed in the cinacalcet and low-dose vitamin D analog treatment group as compared to ﬂexible vitamin D analog group [80]. Studies in uremic animal models showed that calcimimetic is capable of inhibiting vascular calciﬁcation in contrast to calcitriol which induces vascular calciﬁcation [81, 82]. In the ADVANCE trial, a prospective, randomized, controlled trial that evaluated the progression of vascular and cardiac valve calciﬁcation in 360 prevalent adult hemodialysis patients with secondary hyperparathy- roidism after receiving treatment with cinacalcet plus low- dose vitamin D sterols versus ﬂexible doses of vitamin D sterols alone, a trend towards less progression of coronary artery Agatston calcium score was observed in the cinacalcet- treated group after 52 weeks versus the ﬂexible vitamin D sterol group but did not reach statistical signiﬁcance. The diﬀerence in the corresponding changes in volume scores between the two groups were, however, of statistical signiﬁcance. Furthermore, increases in calcium scores were consistently less in the aorta, aortic valve and mitral valve 5 among subjects treated with cinacalcet plus low-dose vitamin D sterols versus the ﬂexible vitamin D sterol group, and the diﬀerences were signiﬁcant at the aortic valve [83]. These data suggest that the use of cinacalcet may be associated with slower progression of vascular/valvular calciﬁcation as compared to ﬂexible vitamin D sterol-treated patients. We await the results of another randomized trial, namely, the EVOLVE (evaluation of cinacalcet HCl therapy to lower cardiovascular events) study to investigate whether cinacal- cet treatment may confer survival beneﬁt in hemodialysis patients with secondary hyperparathyroidism. There is so far no randomized controlled study in PD population that addresses the issue of vascular/valvular calciﬁcation and clinical outcomes in relation to VDRA or cinacalcet. Thus, we can only lend support from data in hemodialysis patients. Studies in in vitro cell culture model or ex vivo model suggested that aortic calciﬁcation requires the elevation of both calcium and phosphorus and that calcium rather than phosphate appears to have a more profound eﬀect on aortic calciﬁcation [63, 84]. However, in PD patients, a low calcium PD ﬂuid may be associated with exacerbation of secondary hyperparathyroidism [85]. Thus, to help reduce calcium loads yet without exacerbating secondary hyper- parathyroidism, the previous K/DOQI guideline suggested that the dialysate calcium concentration in hemodialysis or PD should be maintained at 2.5 meq/L (1.25 mmol/L) [86]. The more recent 2009 KDIGO guideline suggested that the dialysate calcium concentration in hemodialysis or PD patients should be between 2.5 (1.25 mmol/L) and 3 mEq/L (1.5 mmol/L) [75]. A dialysate calcium concentration above 3 meq/L (1.5 mmol/L) is not recommended in dialysis patients as it results in positive calcium balance and increased risk of hypercalcemia [87]. Therefore, maintaining a neutral calcium balance appeared a reasonable goal in managing PD patients. There is so far very little data on the eﬀect of dialysate calcium concentration on vascular calciﬁcation in PD patients. A small nonrandomized study suggested that patients receiving PD ﬂuid of high calcium concentration, namely 1.75 mmol/L showed an increase in arterial stiﬀening as compared to those using low calcium concentration PD ﬂuid which showed no change [88]. These preliminary data suggest that high calcium exposure through PD solution may play a role in progressive arterial stiﬀening through an increase in vascular calciﬁcation and warrant further investigation. 8. Conclusions Vascular and valvular calciﬁcations are equally highly preva- lent in ESRD patients receiving PD treatment as in hemodial- ysis patients and are predictive of an increased mortality and adverse cardiovascular outcomes. Current therapeutic strategies that may be of use in limiting progressive vascu- lar/valvular calciﬁcation in PD patients are largely linked to management of mineral bone disorder associated with CKD including control of hyperphosphatemia, avoiding hyper- calcemia, and control of secondary hyperparathyroidism. Randomized controlled trials will be required to determine