Shiizaki Kazuhiro, Hatamura Ikuji, Negi Shigeo, Narukawa Nobuhiko, Mizobuchi Masahide, Sakaguchi Toshifumi, Ooshima Akira, Akizawa Tadao
Center of Blood Purification Therapy, Wakayama Medical University, Wakayama, Japan.
Kidney Int. 2003 Sep;64(3):992-1003. doi: 10.1046/j.1523-1755.2003.00154.x.
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.
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.
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.
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.
高水平的甲状旁腺激素(PTH)被认为是透析患者预后不良和生活质量差的指标;因此,已开发出一种有效且安全的继发性甲状旁腺功能亢进(SHPT)治疗方法。
对20例对静脉注射帕立骨化醇(OCT)耐药的SHPT患者,在超声引导下对所有可检测到的增大的甲状旁腺进行连续6次经皮帕立骨化醇注射治疗(PMIT),随后静脉注射OCT。根据血清完整PTH、校正钙、磷和骨标志物水平的变化以及超声测定的甲状旁腺体积评估PMIT的临床效果。使用活检技术获取的甲状旁腺组织进行形态学检查、凋亡分析以及通过逆转录聚合酶链反应(RT-PCR)测定PTH mRNA表达水平。
PMIT及随后的静脉注射OCT在PMIT后至少12周显著降低了血清完整PTH水平和甲状旁腺体积,且无主要并发症。PMIT后获取的甲状旁腺组织显示甲状旁腺细胞存在部分缺陷、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记(TUNEL)阳性细胞数量显著增加、DNA电泳确定的梯状条带形成以及PTH mRNA表达水平降低。
PMIT治疗难治性SHPT有效且安全,局部高水平的OCT可抑制PTH分泌并使甲状旁腺增生消退,这与甲状旁腺细胞凋亡的诱导有关。