The ups and downs of dialysate calcium concentration in haemodialysis patients.

The absence of consensus on what should be the ideal dialysate calcium (DCa) concentration in haemodialysis patients is in part explained by the continuously changing therapeutic practice, but also on the scanty evidence that has been produced on this topic. The lack of consistent studies in this field is in part due to a number of methodological limitations for the assessment of both the global external and dialysis calcium balance. Some recent studies, one of which was published in the present issue of the NDT Journal, have added some important information in this field. The main aim of the present editorial is to comment on these recent contributions and also to focus on the foremost limitations and difficulties in the execution of calcium balance studies and their interpretation. The question of what should be the ideal dialysate calcium (DCa) concentration has troubled nephrologists from the earliest days of the dialysis history and still troubles them. The persistence of uncertainties concerning this issue is in part due to the continuously changing scenario in the therapeutic approach to the control of secondary hyperparathyroidism (SHP) and of the related mineral metabolism changes. In fact, at the very beginning of the dialysis history, a DCa close to the physiological concentration of ionized calcium (iCa) in the blood (1.25 mmol/ L) was used. At that time, no effective drug was available for the control of SHP and consequently hypocalcaemia and severe SHP were almost invariably observed. To overcome these problems, in the following years, a DCa of 1.75 mmol/L was recommended [1], which was used for a long time, even after calcium-based phosphate binders (PiBs) almost completely replaced aluminum hydroxide and when calcitriol and other potent vitamin D analogues became available. This translated into an increased extraand intra-dialytic burden of calcium, an over-suppression of parathyroid hormone (PTH) with a consequent increased prevalence of adynamic bone disease (ABD) and probably an increased risk of the occurrence of vascular calcifications. The initial awareness of a possible unacceptable positive calcium balance drove nephrologists to lower again the DCa content to 1.50 mmol/L, which was the most widely used concentration in the late nineties. Furthermore, this awareness developed even more after the K/DOQI guidelines, edited in 2003, recommended going back to an even lower DCa (1.25 mmol/L), in association with the suggestion of using a limited maximal dose of calcium-based PiBs [2]. However, also this position continues to date to be the object of conflicting opinions which hamper the achievement of a consensus on this matter [3–6]. It is also worth stressing that for the most part, this controversy is also justified by the dearth of clinical and/or experimental evidence needed for filling the large knowledge gaps concerning many critical aspects related to both the global and the dialysis calcium balance. Very recently, some papers (one of which has been published in the present issue of NDT) added some additional and, in my opinion, important points in this much debated subject [7–9]. In light of these recent studies, I would like to briefly comment on some of the main unsolved questions concerning calcium balance in haemodialysis patients, considered as both the global external and the dialysis-limited balance. The global external calcium balance (GECaB) can be simply defined as the algebraic sum of the calcium intake minus calcium losses (GECaB in healthy people is broadly described in Figure 1). In a healthy and metabolically stable person, with the assumption that the net calcium movement from and to the internal compartments (the bone-exchangeable pool, mineralized bone compartments, other internal miscible pools, intracellular stores, etc.) is null, GECaB is expected to be close to 0, with the urinary calcium excretion matching the net intestinal calcium absorption (ICaA) (dietary minus fecal calcium amount). However, this basic assumption is not altogether true since these as yet not completely defined ‘internal calcium compartments’ are far from being in a constant steady-state condition, i.e. the inward and outward transfers do not completely match each other at any given time. Hence, for a precise assessment of the real GECaB and the net ICaA we should measure the amount of calcium of the diet and the calcium losses through the