Effects of Lowering Dialysate Calcium Level on Progression of Coronary Artery Calcification and Bone Histomorphometry

Study Overview
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Brief Summary
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The high rate of cardiovascular complications in the dialysis population cannot be explained by traditional cardiovascular risk factors. One of such factors proposed to contribute to the cardiovascular mortality in dialysis patient population is vascular calcification possibly resulting from disturbances of calcium-phosphate metabolism. The aim of this study is to assess the effects of treatment with dialysate containing 1.75 or 1.5 mmol/L to 1.25 mmol/L calcium regarding coronary artery calcification and bone histomorphometry in hemodialysis patients.

Detailed Description
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Sample size calculations were based on previously reported changes in coronary artery calcification scores in hemodialysis patients during time (90% power with a two-sided, alpha error rate of 5%). Four hundred fifty-seven hemodialysis patients, taking drop-out rate into consideration, will be enrolled in this prospective-controlled study.The cases already being treated with calcium-based phosphate binder and dialysate containing 1.75 or 1.5 mmol/L calcium will be enrolled from eight hemodialysis centers.The cases will be randomized to two arms: Dialysate containing 1.25 mmol/L calcium + calcium-based phosphate binder group: Dialysate calcium will be reduced from 1.75 or 1.5 mmol/L to 1.25 mmol/L in this group. Patients will use calcium-based phosphate binder according to phosphate level. Dialysate containing 1.75 mmol/L calcium + calcium-based phosphate binder group (Control group): Dialysate calcium will remain or switched to 1.75 mmol/L and patients will be on calcium-based phosphate binder. The study will last for 18 months.Coronary artery calcification (Multi-slice CT), bone histomorphometry, and bone mineral density will be assessed in the beginning and at the end of the study. Coronary artery calcification and bone mineral density will be measured in all patients; bone histomorphometry will be assessed in 150 patients, 75 from each group.

Official Title
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The Effects of Lowering Dialysate Calcium Level on Progression of Coronary Artery Calcification and Bone Histomorphometry: Prospective, Randomized, Controlled Study

Conditions
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End-Stage Renal Disease, Hemodialysis

Intervention / Treatment
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* Drug: Low dialysate calcium
* Drug: high dialysate calcium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 80 years On maintenance bicarbonate hemodialysis scheduled thrice weekly, at least 12 hours/week To be treated with a dialysate containing 1.75 or 1.5 mmol/L calcium Willingness to participate in the study with a written informed consent Exclusion Criteria: To be scheduled for living donor renal transplantation To have serious life-limiting co-morbid situations, namely active malignancy, active infection, end-stage cardiac, pulmonary, or hepatic disease Pregnancy or lactating To be unable to give informed consent because of mental incompetence or a psychiatric disorder To be on vitamin D treatment within six months of randomization or having iPTH values over target levels (>300 pg/mL) Hypercalcemia (Ca >10.5 mg/dl) with use of dialysate containing 1.75 or 1.5 mmol/L calcium

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2<br>high dialysate calcium | Drug: high dialysate calcium<br>* 1.75 mmol/L dialysate calcium<br>|
| Active Comparator: 1<br>low dialysate calcium | Drug: Low dialysate calcium<br>* 1.25 mmol/L dialysate calcium<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of coronary artery calcification scores |  | eighteen months | 
| Changes in bone histomorphometry analysis |  | eighteen months | 
| Changes in bone mineral density |  | eighteen months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in intact PTH levels |  | eighteen months | 
| effects of dialysate with or without glucose (e.g intradialytic hypoglycemia and hypotension, arrythmia-by Holter ECG- and changes in HbA1c, insulin) |  | eighteen months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemodialysis, Coronary artery calcification, Adynamic bone disease, Dialysate calcium, Bone mineral density, Bone histomorphometry