**5. CKD – MBD summary**

40 Chronic Kidney Disease

calcification, as compared with those of placebo. Even worse, the 4D study failed to show a benefit of atorvastatin treatment on the outcome of diabetic dialysis patients. Studies in progress like SHARP (Study of Heart and Renal Protection) and AURORA (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events) failed to show a better understanding of the benefits of correcting atherosclerotic risk factors on cardiovascular events and mortality in patients

An association of vascular calcification with high phosphate intake has so far not been directly demonstrated in uremic patients, probably owing to the fact that it is difficult, if not impossible, to assess phosphate (protein) intake in a quantitative manner over prolonged time periods. Indirect evidence for a role of oral phosphate, however, has recently been provided by Russo et al (Russo et al., 2007). They showed that in patients with CKD stage 3- 5, coronary artery calcification score progressed significantly over a time period of 2 years, in association with a significant increase in phosphaturia. Many pharmaco-epidemiologic studies have shown a survival benefit in CKD patients receiving active vitamin D derivatives, as compared to those who did not receive such treatments. Finally, let us not forget that association does not imply causation. We clearly need randomized prospective trials showing that active reduction of serum phosphorus, PTH, or alkaline phosphatases and normalization of serum calcium leads to an improvement in patient outcomes, and that specific treatments given to the patients improve outcome, as compared to either placebo or

To date, there are no published prospective studies in humans that have evaluated the impact of calcimimetics or calcitriol and vitamin D analogs on arterial calcification. However, a recent observational study showed a U-curve type of relationship between serum 1,25(OH)2D3 and arterial calcification in children and adolescents with CKD stage 5D. No such association existed between serum 25(OH)D and arterial calcification. In one study in adult patients with CKD stage 5, no independent association of serum 25(OH)D or 1,25(OH)2D3 levels with arterial calcification was observed, (London et al., 2007). Although the authors of another report identified an association between 25(OH)D deficiency and the magnitude of vascular calcification (Matias et al., 2009). The experimental data supporting less toxicity of vitamin D analogs compared with calcitriol are not completely consistent across studies, but, in general, support the claim that there is reduced calcification with equivalent PTH lowering with different vitamin D analogs (Lopez et al., 2008**).** Experimental studies showed differential effects of calcimimetics and calcitriol on extraosseous calcification, the former being neutral or protective, the latter being a dose-dependent risk factor for calcification. In our studies, we have analysed the role of chronic renal failure (CRF) on the arterial wall changes including atherosclerosis and vascular calcifications in CRF apoE-/- mice experimental model (Massy, Ivanovski et al. 2005). Furthermore, we have studied the effect of different non-calcium (Phan et al., 2005) and calcium phosphate binders (Phan et al., 2008) and role of control of phosphatemia on vascular calcification and atherosclerosis (Ivanovski et al. 2009). We have also showed for the first time that the phosphate binder La carbonate is capable of preventing both uremia-enhanced vascular calcification and atherosclerosis in experimental model of CKD (Nikolov et al., 2011). These effects were comparable to those of sevelamer on vascular calcification and atherosclerosis,

as previously reported by us for sevelamer-HCl in this model (Phan et al., 2008).

with CKD stages 3–5 and 5D (Baigent et al., 2003).

other treatments (Drueke and McCarron, 2003).

Mineral and bone disorders are complex abnormalities that cause morbidity and decreased quality of life in patients with CKD. To enhance communication and facilitate research, a new term has been established, CKD–Mineral and Bone Disorder (CKD-MBD), to describe the syndrome of biochemical, bone, and extraskeletal calcification abnormalities that occur in patients with CKD. Also, it has been recommended that the term renal osteodystrophy be used exclusively to define alterations in bone morphology associated with CKD. The latter can be further assessed by histomorphometry, with results reported on the basis of a classification system that includes parameters of turnover, mineralization, and volume. The international adoption of the proposed uniform terminology, definition, and classification to describe these two disorders caused by CKD enhanced communication, facilitated clinical decision making, and can promote the evolution of evidence based clinical-practice guidelines worldwide. This issue of Advances in CKD further describes the clinical manifestations and pathophysiology of CKD-MBD. The optimal management of CKD-MBD (Chronic Kidney Disease – Mineral and Bone Disorder) should be achieved without increasing the risk of metastatic calcification, including that of blood vessels.
