LAUSR

Hypocalcaemia is a well-known effect of the treatment of secondary hyperparathyroidism when using calcimimetics. In a retrospective, observational, study, which was published recently in this Journal [1], Louie et al. investigated the frequency, predictors, and consequences of cinacalcetinduced hypocalcaemia in a cohort of over one thousand haemodialysis patients. They found that hypocalcaemia occurred in more than two third of the treated patients and was mild in many cases. Nonetheless, in one third it was moderate (1.87– < 2.0 mmol/L; 23%) or even severe (< 1.87 mmol/L; 9%). These results coming from a “realworld” setting raise questions on the true potentially negative impact of hypocalcaemia per se or of its treatment, including the increase of dialysate calcium concentration. In this study, intact parathyroid hormone (iPTH) did not increase following hypocalcaemia and, most importantly, the rates of death and cardiovascular events were comparable between hypocalcaemic and non-hypocalcaemic patients. Moreover, non-significant changes occurred in the dialysis schedule and in drug prescriptions over the study. However, a dialysate calcium concentration > 1.5 mmol/L was used in a significant percentage of patients. In the presence of hypocalcaemia, this is expected to increase significantly the intradialytic calcium mass balance, at standard ultrafiltration rate, with possibly unfavourable clinical effects in the long term. Considering that the cardiovascular follow up was limited to 12 months, this question cannot be answered by the data of this study. Correcting hypocalcaemia by increasing dialysate calcium means giving the patient a large amount of calcium in a few hours and in the wrong moment (i.e., simultaneously with the correction of metabolic acidosis!). The management of electrolyte balance is critical in chronic kidney disease (CKD), sometimes requiring emergency intervention in life-threatening situations. In patients with CKD stage-5 dialysis (CKD-5D), the management of electrolyte balance is even more complicate, since haemodialysis is usually performed three times a week for 4 h with a great impact, among the rest, on the body fluid compartments, electrolyte mass balance and concentrations. In this respect, the role of the dialysate composition is of key importance, in particular for calcium. Indeed, CKD 5D patients are at high risk of cardiovascular and parenchymal calcifications, which heavily affect long-term outcome; the regulation of calcium metabolism is hence critical. In this context, the choice of an adequate dialysate calcium concentration (d[Ca]) is an important aspect. Despite this, the topic has been hotly debated, and many grey areas still need clarifications. To confirm this, most of the recommendations of recent guidelines are mainly based on experts’ opinions, with only a few based on evidence [2]; and the adequate d[Ca] in relation to the patient ionized plasma water calcium concentration is among the debated issues [3, 4], particularly when using calcimimetics for the treatment of secondary hyperparathyroidism (SHPT). Today, calcimimetics, such as cinacalcet and etelcalcetide, represent the treatment of choice of SHPT in many patients. Differing from vitamin D sterols, they do not increase serum levels of calcium phosphate and fibroblast growth factor 23 (FGF23) (a hormone associated with cardiovascular mortality in dialysis patients [5]). Nonetheless, they produce hypocalcaemia, which inevitably affects intradialytic calcium balance. There is general agreement that an adequate d[Ca] is needed to prevent or at least reduce the clinical complications of severe SHPT, including cardiovascular, parenchymal * Sandro Mazzaferro [email protected]