International Journal of Nephrology and was similar to that of hemodialysis patients (50%) [35]. This is very similar to our survey showing that around 40% of Chinese PD patients had serum phosphorus level above the K/DOQI target [38]. One of the major clinical factors associated with hyperphosphatemia in PD patients was dietary protein intake. Residual renal function is the other signiﬁcant factor associated with serum phosphorus control in PD patients. Its importance outweighed that of PD clearance among those with preserved residual kidney function. On the other hand, among anuric PD patients, serum phosphorus showed the strongest correlation with PD clearance followed by normalized dietary protein intake [38]. Additionally, a total urea clearance of at least 2.0 and creatinine clearance of at least 60 L/wk per 1.73 m2 appeared to be optimal clearance targets that maintain serum phosphorus below 5 mg/dL in continuous ambulatory PD patients. Given that it is extremely diﬃcult to achieve a total weekly creatinine clearance of over 60 L with PD alone, these data suggest potential limitation of PD alone to achieve ade- quate phosphorus control in anuric PD patients. In keeping with these observations, our recent study demonstrated an increased prevalence of valvular calciﬁcation among anuric PD patients and was partly mediated via an increased calcium ∗ phosphorus product [39]. Apart from alterations in phosphorus metabolism, some of the therapeutic strategies for abnormal mineral metabolism and renal bone disease have been suggested to have the potential of worsening vascular calciﬁcation in ESRD patients [8, 40]. The use of very high doses of calcium- based binders for phosphorus control [8] as well as the administration of large doses of vitamin D analogs for con- trol of secondary hyperparathyroidism [40] may contribute to episodes of hypercalcemia and/or hyperphosphatemia and may thus aggravate vascular calciﬁcation. Chertow and coworkers have shown in a longitudinal study that calcium-based phosphate binders are especially associated with progressive coronary artery and aortic calciﬁcation in hemodialysis patients when mineral metabolism is poorly controlled [41]. Patients with low bone activity appeared to be particularly susceptible to worsening of vascular calciﬁca- tion and stiﬀening when exposed to an excess calcium load [42]. This may be due to the inability of adynamic bone to incorporate extra calcium load and thus increases the risk of extraskeletal calciﬁcation. 6. Pathogenesis of Vascular/Valvular Calciﬁcation Vascular/valvular calciﬁcation is now recognized to be an active, cellular-mediated process involving an osteogenic phenotypic change of vascular smooth muscle cells along with the dynamic interactions between calciﬁcation induc- ers and inhibitors. Inﬂammation may act as one of the potential stimulus for calciﬁcation. This is ﬁrst evident by the accumulation of macrophages and T-lymphocytes other than low-density lipoprotein and Lp(a) lipoprotein in early aortic valve calciﬁcation [43, 44]. Subsequent study from our group showed an important link between inﬂammation and valvular calciﬁcation in PD patients [17]. Among patients 3 with high calcium ∗ phosphorus product, the presence of both inﬂammation and malnutrition increased the preva- lence of valvular calciﬁcation as compared to those with no evidence of inﬂammation and malnutrition. Notably, even among patients with normal calcium ∗ phosphorus product, the presence of inﬂammation and malnutrition was associated with at least twofold increase in the prevalence of valvular calciﬁcation as compared to those with no inﬂammation or malnutrition at all [17]. These data suggest that inﬂammation is predictive of an increased risk of valvular calciﬁcation independent of calcium ∗ phosphorus product. The presence of inﬂammation also predicts a more adverse clinical outcome among PD patients with valvular calciﬁcation [45]. Histopathological study showed markedly increased expression of C-reactive protein messen- ger ribonucleic acid (mRNA) in the coronary vessels of renal patients compared to nonrenal patients in both calciﬁed and noncalciﬁed parts of arteries [29], suggesting that uremia itself was associated with increased vascular inﬂammation and that may mediate the development of vascular calciﬁca- tion. This is further supported by in vitro data showing that pooled uremic serum can induce accelerated calciﬁcation of vascular smooth muscle cells, regardless of the level of phosphorus. However, the exact uremic toxins that increase vascular calciﬁcation are currently not clear. In hemodialysis patients, C-reactive protein showed similar association with annualized change in coronary artery calcium score [46] and has been associated with progression of abdominal calciﬁcation [47]. Inﬂammation has also been inversely related to circulating fetuin-A or alpha-Heremans-Schmid glycoprotein (AHSG) in both hemodialysis and PD patients [48, 49]. These data add circumstantial evidence to support possible causal link between inﬂammation and calciﬁcation and warrant further investigation. Circulating calciﬁcation inhibitors are increasingly rec- ognized to play an important role in modifying the calci- ﬁcation risk of ESRD patients. The presence of extensive calciﬁcation in various organs including the kidneys, lungs, myocardium, skin, and blood vessels in AHSG or fetuin- A deﬁcient mice being fed a mineral and vitamin D rich diet provides novel evidence to support a crucial role of fetuin-A in inhibiting ectopic calciﬁcation [50]. Even though some studies suggested higher fetuin-A levels in PD than hemodialysis patients [51], lower serum fetuin-A was linked to an increased risk of all-cause mortality and cardiovascular death in both hemodialysis [48] and PD patients [49]. Lower fetuin-A was associated with more inﬂammation and valvular calciﬁcation in PD patients [49] and was inversely related to more aortic calciﬁcation in pediatric dialysis patients [52]. All these data lent supporting evidence that fetuin-A may be involved in inhibiting vascular and valvular calciﬁcation. Other circulating inhibitor such as pyrophosphate has recently been shown to be inversely related to the severity of coronary artery calciﬁcation [53] and its circulating level did not seem to be aﬀected by the severity of kidney disease, the modality of dialysis or inﬂammatory activity [53]. Matrix gla-protein (MGP) belongs to a family of the N- terminal γ-carboxylated (Gla) proteins that require a vitamin