Vitamin D and Carboxy PTH Fragments in Coronary Calcification

• Status: Withdrawn
• Trial end date: 2009-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Arterial calcification within the coronaries and other vessels is greatly accelerated among patients with chronic or end-stage kidney disease. The mechanisms leading to increased calcification are unknown, but include hyperphosphatemia, hyperparathyroidism and altered vitamin D metabolism. Moreover, recent data demonstrates that circulating carboxy fragments of PTH (7-84) are physiologic antagonists of intact PTH (1-84) and may directly contribute to vascular calcification. Current PTH assays no not distinguish between intact and carboxy PTH fragments leading to an overestimation of intact PTH levels. Because second generation PTH assays detect both 1-84 and 7-84 PTH fragments, the use of vitamin D analogues to treat secondary hyperparathyroidism could lead to excessive suppression of 1-84 and a preponderance of carboxy PTH fragments. Moreover, increased administration of vitamin D analogues amy contribute to vascular calcifications. To investigate these questions, we plan to investigate the effect of managing new ESRD patients using conventional and third generation PTH assays on vitamin D administration and the development of coronary calcification. Hypothesis #1: Clinical management of secondary hyperparathyroidism in new hemodialysis patients using the Scantibodies 1-84/7-84 PTH ratio for one year will reduce the amount of Vitamin D administration resulting in reduced coronary calcification compared to patients in which PTH management is accomplished by conventional, second generation PTH assay.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Southeast Renal Research Institute
• Treatments: 1 alpha-hydroxyergocalciferol; Ergocalciferols; Vitamin D

Criteria

Inclusion Criteria:

1. Patient age > 18 and < 80 years of age

2. Patients receiving outpatient hemodialysis for > 3 or <24 months duration

3. Patients must have baseline coronary calcification defined as at one ROI (regions of interest with >130 Hounsfield units) in 1 or more coronary vessels

4. Patients must have a stable dose of phosphate binder for 30 days prior to study enrollment

Exclusion Criteria:

1. Patients intact PTH < 100 or > 1000 pg/ml

2. Patients on peritoneal dialysis

3. Patients with a previous parathyroidectomy

4. Patients with dry weight > 300 lbs

5. Patients with chronic atrial flutter or fibrillation

6. Patients receiving chronic coumadin therapy

7. Patients with known allergies to contrast dyes

8. Patients receiving current Cinacalcet therapy or during previous 30 days

9. Patients unable to take Metoprolol therapy

10. Patients with resting heart rate >100 and unresponsive to beta blockade

11. Patients with known pregnancy or unwilling to use contraception during the course of the study

12. Patients unable to tolerate the confines of CT scanner

13. Patients with a renal transplant within the previous 5 years

14. Patients with known aluminum toxicity

15. Patients undergoing recent PTCA or CABG within the previous 12 months

16. Patients with ESRD secondary to Sarcoidosis

17. Patients unwilling to use Selevamer as a primary phosphate binder