Chronotherapy of high-dose active vitamin D3 in haemodialysis patients with secondary hyperparathyroidsm: a repeated dosing study

Abstract

Aims: Renal osteodystrophy is the major complication in patients with end-stage renal failure. Oral or intravenous vitamin D3 (D3) is given to these patients, but severe hypercalcaemia sometimes interrupts this therapy. This study was undertaken to determine whether the effectiveness and safety of D3 also depend on its dosing time during a repeated treatment.

Methods: A higher dose (3 micro g) was given orally to 13 haemodialysis patients at 08.00 h or 20.00 h for 12 months by a randomized, cross-over design.

Results: Three patients were withdrawn due to severe hypercalcaemia after switching from 08.00 h to 20.00 h dosings. The elevation in serum calcium concentration was significantly (P < 0.001) greater during the 08.00 h dosing in the remaining ten patients. Mean serum Ca concentration after the trial was 10.92 (95% confidence interval (CI) 10.79, 11.06) and 9.55 mg dl-1 (95% CI 9.30, 9.71) by 08.00 h and 20.00 h dosing, respectively. On the other hand, the suppression of the elevated serum parathyroid hormone (PTH) and subsequent increment in bone density were significantly greater during the 08.00 h dosing. Mean PTH concentration after the trial was 414 (95% CI 360, 475) and 220 pg ml-1 (95% CI 202, 249) by 08.00 h and 20.00 h dosing, respectively (P = 0.02). Mean increment of bone density after the trial was 22 (95% CI 8, 32) and 57 g cm-3 (95% CI 43, 83) by 08.00 h and 20.00 h dosing, respectively (P = 0.04).

Conclusion: These results indicate that a higher dose of oral D3 is more effective and safe after dosing at evening in patients with renal osteodystrophy.

Figure 1

Individual profile of serum Ca concentration in patient 11 (a), 12 (b) and 13 (c) who suffered from severe hypercalcaemia after switching from evening (□-□) to morning (○-○) dosings of D3.

Figure 1

Individual profile of serum Ca concentration in patient 11 (a), 12 (b) and 13 (c) who suffered from severe hypercalcaemia after switching from evening (□-□) to morning (○-○) dosings of D3.

Figure 1

Individual profile of serum Ca concentration in patient 11 (a), 12 (b) and 13 (c) who suffered from severe hypercalcaemia after switching from evening (□-□) to morning (○-○) dosings of D3.

Figure 2

Serum Ca (a) and P (b) concentrations during morning (□-□) and evening (○-○) dosings of D3. Mean ± SE, n = 10. *P < 0.05 vs morning trial.

Figure 2

Serum Ca (a) and P (b) concentrations during morning (□-□) and evening (○-○) dosings of D3. Mean ± SE, n = 10. *P < 0.05 vs morning trial.

Figure 3

Serum alkaline phosphatase (ALP) (a) and intact parathyroid hormone (PTH) (b) concentrations at morning (□-□) and evening (○- ○) dosings of D3. Mean ± SE, n = 10. *P < 0.05 vs morning trial.

Figure 3

Serum alkaline phosphatase (ALP) (a) and intact parathyroid hormone (PTH) (b) concentrations at morning (□-□) and evening (○- ○) dosings of D3. Mean ± SE, n = 10. *P < 0.05 vs morning trial.

Figure 4

Bone density (a) and its increment from pretreatment level (b) during morning (□-□) and evening (○- ○) dosings of D3. Mean ± SE, n = 10.

Figure 4

Bone density (a) and its increment from pretreatment level (b) during morning (□-□) and evening (○- ○) dosings of D3. Mean ± SE, n = 10.