Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia

Shiizaki, Kazuhiro; Hatamura, Ikuji; Negi, Shigeo; Narukawa, Nobuhiko; Mizobuchi, Masahide; Sakaguchi, Toshifumi; Ooshima, Akira; Akizawa, Tadao

doi:10.1046/j.1523-1755.2003.00154.x

Cited by 52 publications

(44 citation statements)

References 27 publications

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“…It is possible for PTx-AT and percutaneous ethanol injection therapy to decrease the number of PTC that over-synthesize and secrete PTH. Moreover, we previously reported that percutaneous maxacalcitol injection therapy (PMIT) induces apoptosis in PTC and reduces the ultrasonographic PTG volume (10). However, regarding clinical investigations, more invasive examinations are difficult, and the development of direct injection into rat PTG enables further elucidation of these biochemical and cellular effects.…”

Section: Discussionmentioning

confidence: 99%

“…The subsequent intravenous administration of OCT maintained the reduction in serum iPTH level for 4 wk after DI-OCT in u-rats (data not shown). Moreover, we previously reported the maintenance of this decreased level for Ͼ12 wk after PMIT in a clinical investigation (10). The biologic response to medical treatments such as VD that leads to the suppression of PTH synthesis and PTC proliferation is mediated via VDR and CaSR in target cells.…”

Section: Discussionmentioning

confidence: 99%

“…Total RNA (2 g) was reverse-transcribed using oligo (dT) as a primer (Life Technologies) for reverse transcription-PCR (RT-PCR), as in a previous report (10). Subsequently, 1 l of the cDNA mixture was suspended in a total volume of 50 l of a solution that contained 50 mM KCl, 10 mM Tris-HCl, 1.2 mM MgCl 2 , 0.5 M of each primer, 200 M of each nucleotide, and 1 U of Ampli-TaqGold DNA Polymerase (Roche Molecular Systems, Branchburg, NJ).…”

Section: Isolation Of Total Rna and Reverse Transcription-pcr For Pthmentioning

confidence: 99%

“…The most commonly used agent is ethanol, and percutaneous ethanol injection therapy is as effective as PTx-AT (9). Moreover, we previously reported the clinical effects and safety of the direct injection of a highly concentrated VD or its analogue into the PTG of patients with very severe SHPT (10,11).…”

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Biochemical and Cellular Effects of Direct Maxacalcitol Injection into Parathyroid Gland in Uremic Rats

Shiizaki¹,

Negi²,

Hatamura

et al. 2005

Journal of the American Society of Nephrology

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The most important etiological factors of resistance to medical treatments for secondary hyperparathyroidism are the decreased contents of the vitamin D receptor (VDR) and Ca-sensing receptor (CaSR) in parathyroid cells and a severely swollen parathyroid gland (PTG) as a result of hyperplasia. The effects of direct maxacalcitol (OCT) injection into PTG in terms of these factors were investigated in this study. The PTG of Sprague-Dawley rats that were 5/6 nephrectomized and fed a high-phosphate diet were treated by a direct injection of OCT (DI-OCT) or vehicle (DI-vehicle). The changes in serum intact parathyroid hormone (PTH), Ca 2؉, and phosphorus levels, in VDR and CaSR expression levels in parathyroid cells, and in Ca 2؉ -PTH curves were examined. Apoptosis was analyzed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling method and DNA electrophoresis for PTG. DI-OCT markedly decreased serum intact PTH level, and a significant difference in this level between DI-OCT and DI-vehicle was observed. However, serum Ca 2؉ and phosphorus levels did not changed markedly in both groups. The upregulations of both VDR and CaSR, the clear shift to the left downward in the Ca 2؉ -PTH curve, and the induction of apoptosis after DI-OCT were observed. These findings were not observed in the DI-vehicle-treated rats. Moreover, these effects of DI-OCT were confirmed by the DI-OCT into one PTG and DI-vehicle alone into another PTG in the same rat. DI-OCT may introduce simultaneous VDR and CaSR upregulations and the regression of hyperplastic PTG, and these effects may provide a strategy for strongly suppressing PTH levels in very severe secondary hyperparathyroidism. S econdary hyperparathyroidism (SHPT) resulting from ESRD causes not only renal osteodystrophy but also cardiovascular disorders because of ectopic calcification in vascular tissues. A low level of parathyroid hormone (PTH) causes adynamic bone disease; easily increases serum calcium (Ca), phosphorus (P), and CaϫP levels; and may contribute to a poor prognosis in patients with ESRD. Thus, the maintenance of appropriate levels of PTH, Ca, and P is required for the improvement of the prognosis and quality of life of these patients (1-3).SHPT develops in conditions of P retention, low Ca level, and the inactivation of vitamin D (VD) (4 -6); therefore, the control of P level and supplementations of Ca and VD are necessary in patients with SHPT as preventive or medical treatment. However, advanced SHPT with severely swollen parathyroid glands (PTG) as a result of hyperplasia is resistant to these medical treatments because of the low contents of VD receptor (VDR) and Ca-sensing receptor (CaSR) in parathyroid cells (PTC) (7,8). When SHPT progresses into such status, it is considered irreversible. Thus, patients with very severe SHPT require parathyroidectomy-autotransplantation (PTx-AT), which may be complicated by some problems, such as the necessity of general anesthesia, the hyperor hypofunction of autotransplanted PTG, and mental suffering.The ...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Isolation Of Total Rna and Reverse Transcription-pcr For Pthmentioning

confidence: 99%

mentioning

confidence: 99%

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Biochemical and Cellular Effects of Direct Maxacalcitol Injection into Parathyroid Gland in Uremic Rats

Shiizaki¹,

Negi²,

Hatamura

et al. 2005

Journal of the American Society of Nephrology

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“…Alternatively to surgery, ultrasound-guided percutaneous fine-needle ethanol injection into nodular hyperplastic parathyroid glands is very common in Japan (Giangrande et al, 1992;Kitaoka et al, 1994;Fukagawa et al, 1999). Apart from ethanol, also calcitriol or novel VDRA can be directly placed into enlarged parathyroid glands using the same technique (Shiizaki et al, 2003). To date no specific guidelines considering sHPT treatment in hemodialysis patients on kidney transplant waiting list have been established.…”

Section: Parathyroidectomymentioning

confidence: 99%

Management of Secondary Hyperparathyroidism in Hemodialysis Patients

Zitt¹,

Neyer²

2011

Progress in Hemodialysis - From Emergent Biotechnology to Clinical Practice

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The kidney and bone metabolism: Nephrologists' point of view

et al. 2006

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The kidney plays an important role in the regulatory system for bone and mineral metabolism. In chronic kidney disease (CKD), various abnormalities, recently named CKD-mineral and bone disorder (CKD-MBD), may develop in this system. The optimal management of CKD-MBD should be achieved without increasing the risk of metastatic calcification, including that of blood vessels. Thus, it is quite important to identify severe cases of hyperparathyroidism refractory to medical therapy. The size of the parathyroid glands, serum levels of fibroblast growth factor (FGF)23, and, possibly, the overproduction of a novel form of parathyroid hormone (PTH), serve as useful markers for this purpose. Adynamic bone disease with low buffering capacity for calcium is another major cause of hypercalcemia in dialysis patients. Our recent studies suggest that indoxyl sulfate accumulated in uremic serum is responsible for the suppression of osteoblastic function. In order to maintain the bone quality in patients with CKD, bone changes due to aging, menopause, and malnutrition need to be considered by nephrolgists and non-nephrologists in collaboration.

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Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia

Abstract: PMIT is effective and safe for the treatment of refractory SHPT, and a locally high level of OCT suppresses PTH secretion and regresses parathyroid hyperplasia, which is involved in the induction of apoptosis of parathyroid cells.

Cited by 52 publications

References 27 publications

Biochemical and Cellular Effects of Direct Maxacalcitol Injection into Parathyroid Gland in Uremic Rats

Biochemical and Cellular Effects of Direct Maxacalcitol Injection into Parathyroid Gland in Uremic Rats

Management of Secondary Hyperparathyroidism in Hemodialysis Patients

The kidney and bone metabolism: Nephrologists' point of view

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