Bover_EU_Renal.qxp 9/7/07 9:27 am Page 18
Phosphorus Control
Slowing the Progression of Vascular Calcification in
Chronic Kidney Disease Patients
a report by
Jordi Bover, Cristina Canal, Susana G Pérez, Ricardo J Bosch and José A Ballarín
Fundació Puigvert, Hospital de la Santa Creu i Sant Pau, Barcelona; Universitat Autònoma de Barcelona/FP
and Physiology Department, Universidad de Alcalá de Henares, Madrid
Chronic kidney disease (CKD) and particularly end-stage renal disease actively regulated, cell-mediated process resulting from an imbalance
(ESRD) are linked to accelerated vascular disease. One component of this between promoters and inhibitors of mineralisation that has a lot
complex is vascular calcification (VC), a process associated with high of similarities with skeletal mineralisation. Stem cells may be exposed
morbidity as well as elevated cardiovascular (CV) mortality rates in CKD to signals that lead to the initiation of an osteogenic differentiation
patients. VC has also been increasingly recognised in patients with programme.
17
It is also known that multiple proteins and osteogenic
diabetes and osteoporosis. The inverse relationship between bone and markers – such as bone morphogenetic proteins, matrix
VC is becoming an area of great interest,
1
but the pathophysiology and γ-carboxyglutamic acid protein (MGP) and others – are expressed by
connections among bone, VC and poor outcomes are not yet completely vascular smooth muscle cells (VSMCs),
18
VSMCs have also been shown to
understood. Coronary VC is used as a surrogate marker of atherosclerosis express core-binding factor α-1 (Cbfα1)/Runx2 and Sox9
19
– pivotal
since it correlates positively with coronary atherosclerotic plaque burden transcription factors leading VSMCs to osteoblastic and chondrocytic
and plaque instability.
2,3
Despite a poor correlation with angiographic phenotypic differentiation. At the sites of calcification, specific final
findings, calcium scores are an independent predictor of unfavourable products of osteoblast cell-lines such as osteocalcin or alkaline
outcomes in ESRD patients.
3,4
VC is not a new phenomenon, but rather phosphatase have been detected.
18
In any case, when mineral imbalance
a rediscovered one,
5
and it is considered a ‘non-traditional’ CV risk factor occurs, synergistic effects are observed when elevated levels of calcium
contributing to the disproportionate mortality among patients with CKD.
6
and phosphate appear together.
20,21
Additionally, in the presence of
increased intracellular phosphate, the sodium-dependent phosphate
The Scope of the Problem co-transporter Pit-1 signals through Cbfα1 to induce osteoblastic
Vascular calcification is a common feature in both prevalent and incident differentiation of vascular cells.
21
dialysis patients,
4,7–9
due not only to the increasing numbers of elder and
diabetic patients in dialysis programmes, but also to the uraemic milieu Not all proteins regulating VC are locally produced at their site of
favouring VC at the expense of bone demineralisation.
10
Even young and action. A systemic negative acute-phase-reactant protein such as
pre-dialysis patients often have VC.
11–13
The availability of new drugs fetuin-A is an important circulating factor that acts as a potent inhibitor
beyond calcium-containing phosphate binders (CCPBs) and old active of hydroxyapatite crystal formation and expansion.
22,23
Inflammation
forms of vitamin D have also attracted additional interest to VC. We have reduces hepatic fetuin-A synthesis, and it has been shown that fetuin-
also learned that it is not only the severe forms of secondary A levels are significantly lower in haemodialysis patients and are
hyperparathyroidism that are associated with VC: low levels of inversely related to C-reactive protein.
23
Other local and circulating
parathyroid hormone (PTH), probably by preventing the calcium- inhibitors of VC – such as pyrophosphates or magnesium – are altered
buffering ability of bone, could also favour the increasing prevalence of in ESRD patients.
24
low-turnover adynamic bone disease and VC.
14
Resistance to the action
of PTH is a well-known feature of CKD;
15–16
thus, treatment guidelines Both intimal and medial (Mönckeberg’s) calcification – associated with
recommend higher than normal PTH levels to maintain normal bone increased mortality through atherosclerosis and arteriosclerosis,
turnover and avoid VC. respectively – are present in patients with CKD. It is not the scope of this
article to analyse thoroughly either the pathophysiology of VC, the
Over the past few years, we have also learned that VC is not just a passive differences between intimal and medial VC or the different techniques
deposition of calcium and phosphorus in the vascular wall,
10
but also an available to assess VC in CKD patients; however, we suggest that the
readers review some very good artcles on these topics.
1,3,21,25,26
Jordi Bover is a member of the Nephrology Department,
Fundació Puigvert, Hospital de la Santa Creu i Sant Pau,
Attenuation of Progression of Vascular
Barcelona and Professor of Nephrology Research at Calcification by Sevelamer
Universitat Autonoma de Barcelona/FP. His principal
A high phosphate burden not only induces severe secondary
research interests are chronic kidney disease (CKD) and the
pathophysiology of the CKD-mineral and bone (MBD)
hyperparathyroidism, but also blocks all possible attenuating counter-
disorder. He has published extensively on numerous aspects
regulatory mechanisms.
16,27
Moreover – in addition to age – diabetes,
of renal disease in prestigious international journals and has
dialysis vintage or hypertension, hyperphosphataemia, hypercalcaemia
contributed chapters to key international nephrology
textbooks and Spanish counterparts. Dr Bover completed his
(and thus a high calcium and phosphate product), a high intake of
nephrology specialisation and PhD in Barcelona.
calcium by CCPBs, proteinuria, oxidative stress and inflammatory factors
E: jbover@fundacio-puigvert.es have all been related to VC.
1,11–12,20–21,26,28–29
The contribution of CCPBs to
VC has been disputed by others.
29,30
Hyperphosphataemia has been
18 © TOUCH BRIEFINGS 2007
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