Calcium and the saga of the binders: accumulating controversy, or building consensus?

Abstract

At the heart of the oral phosphate binder debate is whether, with the abandonment of aluminium as the main phosphate binder for dialysis patients and its substitution by calcium salts from the early 1980s, we have unleashed a ‘‘weapon of mass calcification’’ by engendering a positive ‘‘calcium balance’’ favouring extensive/progressive soft tissue calcification. More recently we have realized that the near endemic presence of calcium in the walls of blood vessels of chronic kidney disease patients cannot be viewed with either equanimity or passivity. The process of calcium deposition, in a crystalline structural form, is actively regulated. As such, of course, it has active promoters and inhibitors. Active players in the debate about this controversy include the manufacturers of non-calcium-containing phosphate binders, for whom making a convincing scientific and pharmaco-economic case for a potentially expensive change in prescribing practice has a high priority [1]. The most obvious, and worrying, manifestation of this soft-tissue calcification phenomenon is vascular calcification, with its potentially disastrous trio of cardiovascular complications: coronary artery disease, peripheral vascular disease, and arteriosclerosis [2]. The opening skirmishes in this conflict took place over a decade ago. Braun and his colleagues from Erlangen–Nurnberg [3] conducted what was a technology assessment––to see how the ultra-fast electron-beam CT scanner could interrogate the vascular calcium load in dialysis patients. Forty-nine prevalent dialysis patients were chosen for study, and contrasted with 102 age-matched subjects with suspected or angiographically-proven coronary artery disease. What was shown, in the words of the abstract of the paper, was that ‘‘the coronary artery calcium score was from 2.5-fold to 5-fold higher in the dialysis patients than in the non-dialysis patients’’. A stepwise, multiple regression analysis confirmed the importance of age and hypertension. No correlation between calcium, phosphate, or parathyroid hormone values and the coronary calcium score was identified; however, the calcium score was inversely correlated with bone mass in the dialysis patients (r = 0.47, P \ 0.05). The mitral valve was calcified in 59% of dialysis patients, while the aortic valve was calcified in 55%. A repeat examination of the dialysis patients D. J. A. Goldsmith (&) Renal Unit, Guy’s Hospital, London SE1 9RT, UK e-mail: david.goldsmith@gstt.nhs.uk