Cinacalcet-induced hypocalcemia in a cohort of European haemodialysis patients: predictors, therapeutic approaches and outcomes

Abstract

Background Calcimimetic treatment of secondary hyperparathyroidism in chronic dialysis patients is often followed by hypocalcemia. Methods We investigated the frequency, predictors, consequences and therapeutic responses following cinacalcet-induced hypocalcemia in an incident European hemodialysis cohort of 1068 patients with a cinacalcet prescription. Results Of 905 normocalcemic patients initiating cinacalcet, 67% developed hypocalcemia within 12 months: 68% mild, 23% moderate, 9% severe. Compared to persistently normocalcemic patients, those with severe hypocalcemia were more often diabetic, overweight, had cardiovascular disease, shorter dialysis vintage, used a catheter dialysis access, had fewer active vitamin-D sterols, and exhibited higher CRP and iPTH and lower calcium levels. Multivariate predictors of hypocalcemia included a catheter for vascular access, low albumin and high iPTH. Generally, no therapeutic intervention to prevent hypocalcemia was taken prior to cinacalcet initiation. After the hypocalcemic event, the most common clinical response was no change of the dialysis or medical regimen. Following the hypocalcemic event, iPTH remained low even in those with severe hypocalcemia. The number of deaths and cardiovascular events did not differ between patients with and without hypocalcemia within six months following cinacalcet initiation. Conclusion Two-thirds of cinacalcet initiated patients experienced hypocalcaemia with 9% being severe. Hypocalcemia was mostly asymptomatic, transient (with and without targeted intervention to correct it) and not associated with an increase in cardiovascular events or deaths.

Dialysate calcium concentration during calcimimetic treatment: a neglected issue

“…An integrated (but still empirical) approach encompassing all these factors is needed for a personalized d [Ca] prescription that takes into account the complexity of water and electrolyte fluxes during haemodialysis and which would predictably improve the management of calcium metabolism in CKD-5D patients. In the meanwhile, the results of the present study [1] is further reassuring on the safety of even severe asymptomatic hypocalcaemia associated with calcimimetic therapy.…”

“…At multivariate analysis, central vein catheter as vascular access, low albumin and high iPTH were among the predictors of hypocalcaemia [1]. As reported nearly two decades ago by Polaschegg et al [12], if the double-lumen of a central venous catheter is filled with citrate locking solutions, up to 15% of the solution is spilled into the blood of the patient, causing a decrease of plasma water ionized calcium concentration.…”

“…Interestingly, in the discussion the authors report that short-term adjustments of d[Ca] might not have been captured in severely hypocalcaemic patients and that, in any case, they had no clear evidence for any systematic trend towards higher d[Ca] in those with hypocalcaemia [1]. However, we would have possibly expected a decrease and not an increase in d [Ca].…”

“…In the paper by Louie et al [1], in comparison with those who were normocalcaemic, the patients with severe hypocalcaemia were more often diabetic, overweight, had cardiovascular disease, a shorter dialysis vintage, used a central vein catheter as dialysis access, were prescribed fewer active vitamin D sterols, and had higher C-reactive protein (CRP) Fig. 1 Calcium balance during dialysis is influenced by several factors: diffusion from dialysate to blood; convection from blood to dialysate; changes in pH from acidosis to alkalosis; increments in albumin concentration during dialysis and bone turnover.…”

“…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.…”