The Effect of Increasing Dialysate Calcium on Serum Calcification Propensity in Subjects With Secondary Hyperparathyroidism and End-Stage Kidney Disease
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Secondary Hyperparathyroidism
- Sponsor
- Iain Bressendorff
- Enrollment
- 48
- Primary Endpoint
- Difference in serum calcification propensity (T50)
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
Brief Summary
Patients with end-stage kidney disease (ESKD) have an increased risk of cardiovascular mortality. High parathyroid hormone (PTH) from secondary hyperparathyroidism leads to increased efflux of phosphate and calcium from bone, which exacerbates vascular calcification and increases the risk of bone fractures. The main driving factor for secondary hyperparathyroidism is hypocalcaemia caused by low levels of 1,25-dihydroxy vitamin D and pharmacological supplementation with activated vitamin D and oral calcium-containing phosphate-binders are used to control secondary hyperparathyroidism. The amount of calcium used in this context is controversial, as higher calcium load in blood may theoretically increase vascular calcification. Conversely, by alleviating the efflux of phosphate and calcium from bone due to secondary hyperparathyroidism, increasing the load of calcium might actually prevent vascular calcification.
To study this further, we wish to conduct a randomised double-blinded controlled clinical trial of increasing dialysate Ca from 1.25 mmol/L (standard dialysate concentration) to 1.50 mmol/L in patients with ESKD and secondary hyperparathyroidism on maintenance haemodialysis (HD). The overall effect of increased dialysate calcium will be gauged by its effect on serum calcification propensity (T50) and on markers of bone turnover.
Investigators
Iain Bressendorff
MD PhD
Herlev Hospital
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years.
- •Treatment with thrice-weekly maintenance HD for ESKD for \> 3 months.
- •Dialysate calcium of 1.25 mmol/L (standard concentration).
- •Plasma ionised calcium \< 1.35 mmol/L (average of last 3 months).
- •Plasma intact PTH \> 14 ρmol/L.
- •Plasma total alkaline phosphatase \>90 U/L
- •Negative pregnancy test and use of highly effective and safe contraception.
- •Able to give written informed consent.
Exclusion Criteria
- •Treatment with peritoneal dialysis.
- •Clinical bone fracture within the last 6 months.
- •Treatment with bisphosphonates, denosumab, romosozumab, or teriparatide within the last 3 months.
- •Other diseases or conditions, which, in the opinion of the site investigator, would prevent participation in or completion of the trial.
- •Pregnancy or breastfeeding.
Outcomes
Primary Outcomes
Difference in serum calcification propensity (T50)
Time Frame: 28 days
Between-groups difference in T50 at day 28 adjusted for T50 at day 0
Secondary Outcomes
- Difference in procollagen 1 intact N-terminal propeptide (P1NP)(28 days)
- Difference in tartrate-resistant acid phosphatase 5b (TRAcP 5b)(28 days)
- Difference in calciprotein monomers (CPM)(28 days)
- Difference in bone-specific alkaline phosphatase (bALP)(28 days)
- Difference in parathyroid hormone (PTH)(28 days)
- Difference in primary calciprotein particles (CPP-1)(28 days)
- Difference in primary calciprotein particles (CPP-2)(28 days)
- Difference in plasma ionised calcium (iCa)(28 days)
- Difference in plasma magnesium (Mg)(28 days)
- Difference in all above variables(28 days)
- Difference in plasma phosphate (PO4)(28 days)