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Nephron 1990;55:380-385

Effects on Serum Parathyroid Hormone of Intravenous Treatment with Alphacalcidoi in Patients on Chronic Hemodialysis Sverker Ljunghall, Peter Althoff, Bengt Fellstrom. Biserka Marjanovic, Jonas Nisell, Lars Weiss, L eif Wide Departments of Internal Medicine at Sundsvall, Vdsteris, Mora and Karlstad Hospitals and the Departments of Internal Medicine and Clinical Chemistry, University Hospital, Uppsala, Sweden

Key Words. Parathyroid hormone • Secondary hyperparathyroidism • Chronic renal failure • Calcium • Vitamin D • Alphacalcidoi

Introduction The relationship between parathyroid hormone (PTH), calcium, phosphorus and vitamin D metabolism in chronic renal insufficiency is complex and the under­ standing is still far from clear. It is, however, well docu­ mented that the serum level of PTH rises early in renal failure and often continues to increase with the decline in renal function. Although the actual increase in the serum PTH level may vary, from mild elevation to concentra­ tions many times the upper limit of normal, nearly all renal failure patients show some degree of secondary hyperparathyroidism (HPT) [I, 2). Recognition of the role of l,25(OH)2D3(calcitriol) as a key hormone in the control of calcium and phosphorus homeostasis has led to the concept that deficiency of the active metabolite of vitamin D contributes to the reduc­ tion of plasma calcium and hence to the stimulation of

PTH secretion by decreasing intestinal calcium absorp­ tion and/or by blunting PTH-induced calcium resorp­ tion from bone [3]. When calcitriol is given orally, how­ ever, hypercalcemia is common and even then PTH may not change markedly [4-7] The parathyroid glands possess specific receptors for calcitriol, which decreases the levels of pre-proPTH mRN A in a specific, reversible and dose-dependent fash­ ion from physiologic to pharmacologic levels [8]. It has also been demonstrated in vitro that calcitriol inhibits secretion of PTH regardless of the ambient calcium con­ centrations [9-12], A possible direct effect of this com­ pound has recently been explored in clinical studies. In an investigation where calcitriol was given intravenously to hypocalcemic patients on chronic hemodialysis there was a reduction of elevated PTH levels already before there was any significant increase in the serum calcium level [13],

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Abstract. Secondary hyperparathyroidism is common in chronic renal failure and is due to inadequate synthesis of calcitriol, the active metabolite of vitamin D. Intravenous administration of alphacalcidoi, a synthetic analogue which is metabolized to calcitriol, was given during 12 weeks to 51 patients on chronic hemodialysis in doses between 1and 4 pg/diaiysis session. The treatment caused a modest rise, by 0.25 mmol/l, in serum calcium but a 60% reduction of intact serum PTH concentrations. Most patients acquired normal PTH values and hypercalcemia was easily avoided by dose adjustments. There was a significant reduction in serum PTH within the 1st week before the serum calcium concentrations were increased, but after that time the induced suppression of PTH was correlated to the induced rise in serum calcium. These observations are compatible with the view that calcitriol exerts both a direct inhibition of PTH release and increases the gland's sensitivity to calcium. The major implication of the study is that intravenous treatment with alphacalcidoi is of great clinical value since it is easy to administer and provides suppression of hypersecretion of PTH with few side effects.

Intravenous Treatment with Alphacalcidol

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Table 1. Mean values( ±SD ) before and during treatment with alphacalcidol Time, weeks 0 Calcium (2.20-2.60). mmol/l Phosphate (0.76-1.44), mmol/l PTH (10-55), ng/l PTH (geometric mean)

1

2

3

4

8

12

2.20 ±0.16 2.24 ±0.19 2.30±0.2I*** 2.42 ±0.22*** 2.50 ±0.23*** 2.44±0.I9*** 2.45 ±0.25*** 2.29 ±0.79 2.26 ±0.58 2.07±0.50 2.12±0.52 2.27 ±0.50 2.39 ±0.65** 2.38 ±0.39* 168 ±247 126 ±227 135 ± 199 132 ±209 255 ±291 223 ±248 210 ± 275 160 140** 84*** 49*** 65*** 58*** 113***

The values in parentheses represent normal range. *p

Effects on serum parathyroid hormone of intravenous treatment with alphacalcidol in patients on chronic hemodialysis.

Secondary hyperparathyroidism is common in chronic renal failure and is due to inadequate synthesis of calcitriol, the active metabolite of vitamin D...
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