TY - JOUR
T1 - Percutaneous maxacalcitol injection therapy regresses hyperplasia of parathyroid and induces apoptosis in uremia
AU - Shiizaki, Kazuhiro
AU - Hatamura, Ikuji
AU - Negi, Shigeo
AU - Narukawa, Nobuhiko
AU - Mizobuchi, Masahide
AU - Sakaguchi, Toshifumi
AU - Ooshima, Akira
AU - Akizawa, Tadao
N1 - Funding Information:
Chugai Pharmaceutical Co., Ltd., Tokyo, Japan, supported this study by measuring serum OCT concentrations in patients treated by PMIT and providing OCT and its vehicle for animal experiments. This study was partially supported by a research grant from Renal Osteodystrophy Foundation. The authors thank Dr. Masafumi Kitaoka (Division of Endocrinology and Metabolism, Showa General Hospital, Tokyo, Japan) for the kind training in parathyroid intervention technique under ultrasonography.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - Background. A high level of parathyroid hormone (PTH) is considered to be an indicator of poor prognosis and a poor quality of life of dialysis patients; therefore, an effective and safe therapy for secondary hyperparathyroidism (SHPT) has been developed. Methods. In 20 patients with SHPT resistant to maxacalcitol (OCT) intravenously administered, all detectably enlarged parathyroid glands were treated by percutaneous maxacalcitol injection therapy (PMIT) under ultrasonographic guidance consecutively 6 times, which was followed by OCT that was intravenously administered. The clinical effects of PMIT were evaluated based on the changes in the serum intact-PTH, adjusted Ca, phosphorus, and bone marker levels, and the parathyroid gland volume determined by ultrasonography. Morphologic examination, apoptosis analysis, and PTH mRNA expression level determination by reverse transcription-polymerase chain reaction (RT-PCR) using parathyroid tissues obtained by a biopsy technique were performed. Results. PMIT and subsequent intravenous OCT administrations significantly decreased the serum intact-PTH level and parathyroid gland volume for at least 12 weeks after PMIT without major complications. Parathyroid tissues obtained after PMIT exhibited some partial defects of parathyroid cells, a marked increase in the number of the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)positive cells, the ladder formation determined by DNA electrophoresis, and the decrease in the PTH mRNA expression level. Conclusion. 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.
AB - Background. A high level of parathyroid hormone (PTH) is considered to be an indicator of poor prognosis and a poor quality of life of dialysis patients; therefore, an effective and safe therapy for secondary hyperparathyroidism (SHPT) has been developed. Methods. In 20 patients with SHPT resistant to maxacalcitol (OCT) intravenously administered, all detectably enlarged parathyroid glands were treated by percutaneous maxacalcitol injection therapy (PMIT) under ultrasonographic guidance consecutively 6 times, which was followed by OCT that was intravenously administered. The clinical effects of PMIT were evaluated based on the changes in the serum intact-PTH, adjusted Ca, phosphorus, and bone marker levels, and the parathyroid gland volume determined by ultrasonography. Morphologic examination, apoptosis analysis, and PTH mRNA expression level determination by reverse transcription-polymerase chain reaction (RT-PCR) using parathyroid tissues obtained by a biopsy technique were performed. Results. PMIT and subsequent intravenous OCT administrations significantly decreased the serum intact-PTH level and parathyroid gland volume for at least 12 weeks after PMIT without major complications. Parathyroid tissues obtained after PMIT exhibited some partial defects of parathyroid cells, a marked increase in the number of the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)positive cells, the ladder formation determined by DNA electrophoresis, and the decrease in the PTH mRNA expression level. Conclusion. 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.
KW - DNA fragmentation
KW - In vivo effects
KW - Interventional ultrasonography
KW - Secondary hyperparathyroidism
KW - Send-stage renal disease (ESRD)
KW - Vitamin D analogue
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U2 - 10.1046/j.1523-1755.2003.00154.x
DO - 10.1046/j.1523-1755.2003.00154.x
M3 - Article
C2 - 12911549
AN - SCOPUS:0041429578
SN - 0085-2538
VL - 64
SP - 992
EP - 1003
JO - Kidney international
JF - Kidney international
IS - 3
ER -