End-stage Kidney Disease, Secondary Hyperparathyroidism
Conditions
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.
Interventions
OTHERDialysate calcium 1.50 mmol/L
Increased dialysate calcium of 1.50 mmol/L (as compared to standard dialysate calcium of 1.25 mmol/L)
Sponsors
Iain Bressendorff
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Blinding of participants and investigators. Dialysis nurses will be aware of treatment assignment.
Intervention model description
Randomised, double-blind, parallel-group, controlled clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in serum calcification propensity (T50) | 28 days | Between-groups difference in T50 at day 28 adjusted for T50 at day 0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in primary calciprotein particles (CPP-1) | 28 days | Between-groups difference in CPP-1 at day 28 adjusted for CPP-1 at day 0 |
| Difference in bone-specific alkaline phosphatase (bALP) | 28 days | Between-groups difference in bALP at day 28 adjusted for bALP at day 0 |
| Difference in procollagen 1 intact N-terminal propeptide (P1NP) | 28 days | Between-groups difference in P1NP at day 28 adjusted for P1NP at day 0 |
| Difference in tartrate-resistant acid phosphatase 5b (TRAcP 5b) | 28 days | Between-groups difference in TRAcP 5b at day 28 adjusted for TRAcP 5b at day 0 |
| Difference in parathyroid hormone (PTH) | 28 days | Between-groups difference in PTH at day 28 adjusted for PTH at day 0 |
| Difference in primary calciprotein particles (CPP-2) | 28 days | Between-groups difference in CPP-2 at day 28 adjusted for CPP-2 at day 0 |
| Difference in plasma ionised calcium (iCa) | 28 days | Between-groups difference in iCa at day 28 adjusted for iCa at day 0 |
| Difference in plasma phosphate (PO4) | 28 days | Between-groups difference in PO4 at day 28 adjusted for PO4 at day 0 |
| Difference in plasma magnesium (Mg) | 28 days | Between-groups difference in Mg at day 28 adjusted for Mg at day 0 |
| Difference in all above variables | 28 days | Within-groups difference in all above variables at day 28 adjusted for values at day 0 |
| Difference in calciprotein monomers (CPM) | 28 days | Between-groups difference in CPM at day 28 adjusted for CPM at day 0 |
Contacts
Primary ContactIain Bressendorff, MD PhD
Backup ContactDitte Hansen, MD PhD
Outcome results
None listed