• Calcium
• cardiac arrest
• emergency department
• outcomes
• survival

• Delta calcium
• Delta magnesium
• Hemodialysis
• QTc prolongation

• Calcium
• Cross-Sectional Studies
• Electrocardiography
• Electrolytes
• Female
• Hemodialysis Units, Hospital
• Humans
• Long QT Syndrome/etiology
• Magnesium
• Male
• Renal Dialysis/adverse effects
• Risk Factors
• Urologic Diseases
• Water-Electrolyte Imbalance/etiology

• Arrhythmia
• Cardiovascular disease
• Dialysis
• Kidney
• Sudden cardiac death

• Cardiovascular Diseases/complications
• Cardiovascular Diseases/genetics
• Case-Control Studies
• Child, Preschool
• Death, Sudden, Cardiac/epidemiology
• Death, Sudden, Cardiac/etiology
• Humans
• Kidney Failure, Chronic/complications
• Kidney Failure, Chronic/genetics
• Kidney Failure, Chronic/therapy
• Renal Dialysis/adverse effects

• R01 DK100306 NIDDK NIH HHS
• UL1 TR002529 NCATS NIH HHS

Secondary hyperparathyroidism (SHPT), a complication of haemodialysis, is commonly treated with calcimimetics. The impact of dialysates containing different calcium (Ca) concentrations on clinical efficacy of calcimimetics are unclear. We examined whether dialysate Ca concentrations influence the efficacy and dosing of etelcalcetide with concomitant drugs.

We performed post hoc analyses of a 52‐week, open‐label, multicentre study of etelcalcetide in Japanese SHPT patients to determine whether dialysate Ca influences the therapeutic effects of etelcalcetide with concomitant drugs. We evaluated the differences in serum intact parathyroid hormone (iPTH), corrected Ca (cCa) and phosphate levels among three dialysate Ca concentration groups (2.5, 2.75 or 3.0 mEq/L Ca). Tartrate‐resistant acid phosphatase 5b (TRACP‐5b) and bone alkaline phosphatase (BAP) levels were also compared. Since the dialysate Ca concentration may influence dose adjustment, we assessed the etelcalcetide and concomitant drug doses.

There were no clinically meaningful differences in iPTH, cCa and phosphate levels among the 2.5, 2.75 and 3.0 mEq/L groups (n = 34, 64 and 35, respectively) over 52 weeks. At Week 52, more than 82%, 71% and 67% of patients had iPTH, cCa and phosphate levels within target ranges (60‐240 pg/mL, 8.4‐10.0 mg/dL and 3.5‐6.0 mg/dL, respectively) across the three groups. TRACP‐5b and BAP levels decreased by Week 52 regardless of dialysate Ca. Changes in etelcalcetide and concomitant drug doses were generally similar in each group.

The efficacy and dosing of etelcalcetide with concomitant drugs were essentially unaffected by the dialysate Ca concentration. Patients showed improvements in bone hypermetabolism during treatment.

This is a small observational study of the effect of dialysate calcium concentrations on etelcalcetide with concomitant drugs in secondary hyperparathyroidism. No statistically significant differences were found between the different dialysate calcium groups suggesting that calcium concentrations in the dialysate do not modulate the effect of etelcalcetide.

• bone metabolism
• calcimimetics
• calcium dialysate
• etelcalcetide
• secondary hyperparathyroidism

• Calcimimetics
• Controversies in management of secondary hyperparathyroidism
• Phosphate binders
• Secondary hyperparathyroidism
• Vitamin D analogs

• Calcimimetic Agents/therapeutic use
• Chelating Agents/therapeutic use
• Humans
• Hyperparathyroidism, Secondary/drug therapy
• Hyperparathyroidism, Secondary/etiology
• Hyperphosphatemia/drug therapy
• Hyperphosphatemia/etiology
• Hypocalcemia/drug therapy
• Hypocalcemia/etiology
• Parathyroid Hormone/blood
• Phosphorus/blood
• Renal Insufficiency, Chronic/complications
• Vitamin D/therapeutic use

• K23 DK114556 NIDDK NIH HHS

• Sudden cardiac death
• electrolytes
• hemodialysis
• volume

Prolonged QT interval in hemodialysis patients may be associated with sudden cardiac death, however, few studies examined the longitudinal associations of modifiable factors such as serum and dialysate concentrations of calcium, potassium, and magnesium with corrected QT (QTc) prolongation in incident hemodialysis patients.

In 330 in-center hemodialysis participants from the PACE study who were followed up for one year, we examined the associations of predialysis serum electrolytes (total calcium [Ca], corrected Ca [cCa], ionized Ca [iCa], potassium [K], magnesium [Mg]), dialysate (dCa and dK), and serum-to-dialysate gradient measures with QTc interval and prolongation (≥460 ms in women and ≥ 450 ms in men).

At the first study visit, 47% had QTc prolongation. Lower iCa and K were associated with longer QTc interval independent of potential confounders (QTc difference = 8.55[95% CI: 2.13, 14.97] ms for iCa; QTc difference = 9.89[1.58, 18.20] ms for K). Lower iCa was also associated with a higher risk of QTc prolongation. At 1 year of follow-up, 31% had persistent QTc prolongation. In longitudinal analyses, the associations of iCa and K with QTc interval remained significant, and lower K was associated with a higher risk of QTc prolongation while the association of iCa with QTc prolongation was borderline statistically significant. Serum Mg, dCa or dK, and respective gradients were not associated with QTc interval or prolongation.

Prolonged QTc is very common in incident hemodialysis participants and persists over follow-up. Ionized Ca and K are consistently inversely associated with QTc prolongation, which suggests closer monitoring for a low calcium or potassium level to mitigate risk.

The online version of this article (10.1186/s12882-019-1282-5) contains supplementary material, which is available to authorized users.

• Arrhythmia
• Electrolytes
• Hemodialysis
• QT interval
• QT prolongation

Dialysate calcium concentration (d[Ca]) might have a cardiovascular impact in patients on haemodialysis (HD) since a higher d[Ca] determines better hemodynamic tolerability. We have assessed the influence of d[Ca] on global longitudinal strain (GLS) by two-dimensional echocardiography using speckle-tracking imaging before and in the last hour of HD. This is an observational crossover study using d[Ca] 1.75 mmol/L and 1.25 mmol/L. Ultrafiltration was the same between interventions; patients aged 44 ± 13 years (N = 19). The 1.75 mmol/L d[Ca] was associated with lighter drop of blood pressure. Post HD serum total calcium was higher with d[Ca] 1.75 than with 1.25 mmol/L (11.5 ± 0.8 vs. 9.1 ± 0.5 mg/dL, respectively, p < 0.01). In almost all segments strain values were significantly worse in the peak HD with 1.75 mmol/L d[Ca] than with 1.25 mmol/L d[Ca]. GLS decreased from −19.8 ± 3.7% at baseline to −17.3 ± 2.9% and −16.1 ± 2.6% with 1.25 d[Ca] and 1.75 d[Ca] mmol/L, respectively (p < 0.05 for both d[Ca] vs. baseline and 1.25 d[Ca] vs. 1.75 d[Ca] mmol/L). Factors associated with a worse GLS included transferrin, C-reactive protein, weight lost, and post dialysis serum total calcium. We concluded that d[Ca] of 1.75 mmol/L was associated with higher post dialysis serum calcium, which contributed to a worse ventricular performance. Whether this finding would lead to myocardial stunning needs further investigation.

• mineral metabolism
• vitamin d
• cinacalcet
• phosphorus
• parathyroid hormone

• Calcimimetic Agents/therapeutic use
• Calcitriol/therapeutic use
• Calcium/metabolism
• Chelating Agents/therapeutic use
• Dialysis Solutions
• Drug Therapy, Combination
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors/metabolism
• Humans
• Kidney Failure, Chronic/metabolism
• Kidney Failure, Chronic/therapy
• Parathyroid Hormone/blood
• Phosphorus/metabolism
• Renal Dialysis
• Vitamin D/therapeutic use

• P30 DK096493 NIDDK NIH HHS
• R01 DK111952 NIDDK NIH HHS

• Humans
• Hyperparathyroidism, Secondary
• Kidney Failure, Chronic

• U01 DK099930 NIDDK NIH HHS
• R01 DK076116 NIDDK NIH HHS
• R01 DK081374 NIDDK NIH HHS
• K24 DK093723 NIDDK NIH HHS
• R01 DK094796 NIDDK NIH HHS

• Epidemiology
• Haemodialysis
• Mechanism
• Sudden cardiac death

The removal of calcium during hemodialysis with low calcium concentration in dialysis fluid is generally slow, and the net absorption of calcium from dialysis fluid is often reported. The details of the calcium transport process during dialysis and calcium mass balance in the extracellular fluid, however, have not been fully studied.

Weekly cycle of three dialysis sessions with interdialytic breaks of 2-2-3 days was monitored in 25 stable patients on maintenance hemodialysis with calcium concentration in dialysis fluid of 1.35 mmol/L. Total and ionic calcium were frequently measured in blood and dialysate. The volume of fluid compartments was measured by bioimpedance.

Weekly dialytic removal of 12.79 ± 8.71 mmol calcium was found in 17 patients, whereas 9.48 ± 8.07 mmol calcium was absorbed per week from dialysis fluid in 8 patients. Ionic calcium was generally absorbed from dialysis fluid, whereas complexed calcium (the difference of total and ionic calcium in dialysis fluid) was removed from the body. The concentration of total calcium in plasma increased slightly during dialysis. The mass of total and ionic calcium in extracellular fluid decreased during dialysis in patients with the dialytic removal of calcium from the body and did not change in patients with the absorption of calcium from dialysis fluid.

We conclude that about one third of patients on dialysis with calcium 1.35 mmol/L in dialysis fluid may absorb calcium from dialysis fluid and therefore individual prescriptions of calcium concentration in dialysis fluid should be considered for such patients.