Cellular changes following direct vitamin D injection into the uraemia-induced hyperplastic parathyroid gland

Abstract

Background. Hyperplasia of the parathyroid gland (PTG) is associated not only with excessive secretion of parathyroid hormone (PTH) but also with changes in the parathyroid cell (PTC) characteristics (i.e. hyperproliferative activity and low contents of vitamin D and calcium-sensing receptors). The control of PTG hyperplasia is most important in the management of secondary hyperparathyroidism (SHPT), because the advanced stage of hyperplasia is considered irreversible. For the better control of the PTH level in dialysis patients with such advanced SHPT, percutaneous vitamin D injection therapy (PDIT) under ultrasonographic guidance was developed and various cellular changes caused by this treatment were also investigated using an animal model.Methods. The PTGs of Sprague–Dawley rats, which had been 5/6-nephrectomized and fed a high-phosphate diet, were treated with the direct injections of vitamin D agents, and cellular effects focusing the above-mentioned characters were investigated.Results. An adequacy of the direct injection technique into the rats’ PTGs and the successful effects of this treatment in various biochemical parameters were confirmed. Such characteristics of advanced SHPT were simultaneously improved; in particular, it was confirmed that this treatment may be effective in controlling PTG hyperplasia by, at least in part, apoptosis-induced cell death.Conclusions. A locally high level of vitamin D strongly may suppress PTH secretion and regress hyperplasia, which is involved in the induction of apoptosis in PTCs, based on the simultaneous improvements of cellular characters of advanced SHPT. The PTH control introduced by this treatment successfully ameliorated osteitis fibrosa (high bone turnover rate).

Surgical or medical therapy for severe hyperparathyroidism or chronic kidney disease? An appraisal of current practice guidelines

“…However, the systemic administration of calcitriol or its active derivatives, even in pulse therapy, gave discordant results in terms of PTG morphology (decrease in dimensions) or function (decrease in PTH levels, calcium-PTH curve left shift), probably because of the reduced number of VDR observed in nodular hyperplastic glands. Recently, Shiizaki et al reported reduction in PTG dimensions (evaluated by sonography), decrease in PTH levels and reversal of PTG responsiveness to calcium in patients with severe sHPT after direct intraparathyroidian injection of an active vitamin D derivative (maxacalcitol) (56). Moreover, they confirmed their clinical results in a mouse model of severe sHPT where apoptosis was demonstrated by light and electron microscopy, TUNEL method and DNA electrophoresis.…”

Suplemen Calcitriol Dosis Tinggi Mencegah Osteoporosis dan Memicu Urolitiasis pada Tikus Ovariektomi

“…Tingginya ekskresi Ca urin pada tikus yang diberi suplementasi calcitriol diduga akibat turunnya hormon paratiroid. Dilaporkan Seamans dan Casman (2009), Ramagnoli et al, (2008 dan Shiizaki et al, (2008) bah wa suplemen 1,25-dihidroksivitamin D 3 menurunkan sekresi hormon paratiroid. Menurut Mihai dan Fardon (2000) hormon paratiroid bekerja pada ginjal untuk meningkatkan reabsorpsi Ca, turunnya hormon paratiroid dengan demikian meningkatkan ekskresi Ca dalam urin.…”