Murakami Kazutaka, Miyachi Hiromi, Watanabe Asako, Kawamura Nahoko, Fujii Mikiko, Koide Shigehisa, Murase Masamitsu, Kushimoto Hiroko, Hasegawa Midori, Tomita Makoto, Hiki Yoshiyuki, Sugiyama Satoshi
Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Toyoake 470-1192, Japan.
Clin Exp Nephrol. 2004 Jun;8(2):134-8. doi: 10.1007/s10157-004-0283-1.
Maxacalcitol (22-oxacalcitriol; OCT) is a novel vitamin D analogue. In previous clinical studies, OCT was administered three times a week to hemodialysis patients with refractory secondary hyperparathyroidism (2HPT), in whom it acted by inhibiting parathyroid hormone secretion, as well as causing mildly elevated serum calcium. However, intravenous injection of OCT, which requires frequent visits to the outpatient clinic, degrades the quality of life of patients with continuous ambulatory peritoneal dialysis (CAPD) who otherwise visit the clinic only once or twice per month. In the present study, we investigated whether transperitoneal absorption of OCT inhibited intact parathyroid hormone (i-PTH) in CAPD patients when the OCT was added to the peritoneal dialysis fluid.
Peritoneal dialysis fluid containing 20 micro g of OCT was injected into the peritoneal cavity of five CAPD patients. The serum and peritoneal fluid levels of OCT, i-PTH, calcium, and phosphate were measured before and after treatment.
The mean concentration of OCT in peritoneal dialysis fluid rapidly decreased, from 25268.0 pg/ml at 0 h to 1694.0 pg/ml at 2 h and 44.9 pg/ml at 4 h. In contrast, the mean serum OCT level increased from the pretreatment level, which was below the detection limit of the assay, to 656.0 pg/ml at 0.5 h and a peak of 759.0 pg/ml at 1 h, and thereafter gradually decreased, to 713.8 pg/ml at 2 h and 555.8 pg/ml at 4 h. Mean i-PTH significantly decreased, to 83.9% of the baseline level, at 1 h (P < 0.05) and thereafter stayed at around 90%. No consistent trends in calcium and phosphate levels were observed in the five patients.
By injecting OCT into the peritoneal cavity, i-PTH levels could be significantly decreased. These findings indicate the therapeutic efficacy of intraperitoneal administration of OCT for CAPD patients.
马沙骨化醇(22-氧杂骨化三醇;OCT)是一种新型维生素D类似物。在以往的临床研究中,OCT每周给药三次用于治疗难治性继发性甲状旁腺功能亢进(2HPT)的血液透析患者,它通过抑制甲状旁腺激素分泌发挥作用,同时导致血清钙轻度升高。然而,静脉注射OCT需要患者频繁到门诊就诊,这降低了持续性非卧床腹膜透析(CAPD)患者的生活质量,这些患者通常每月仅到门诊就诊一两次。在本研究中,我们调查了将OCT添加到腹膜透析液中时,OCT经腹膜吸收是否能抑制CAPD患者的全段甲状旁腺激素(i-PTH)。
将含有20μg OCT的腹膜透析液注入5例CAPD患者的腹腔。在治疗前后测量血清和腹膜液中OCT、i-PTH、钙和磷的水平。
腹膜透析液中OCT的平均浓度迅速下降,从0小时时的25268.0 pg/ml降至2小时时的1694.0 pg/ml和4小时时的44.9 pg/ml。相比之下,血清OCT平均水平从低于检测限的预处理水平升高,在0.5小时时达到656.0 pg/ml,1小时时达到峰值759.0 pg/ml,此后逐渐下降,2小时时为713.8 pg/ml,4小时时为555.8 pg/ml。平均i-PTH在1小时时显著下降至基线水平的83.9%(P<0.05),此后维持在90%左右。5例患者的钙和磷水平未观察到一致的变化趋势。
通过将OCT注入腹腔,可显著降低i-PTH水平。这些发现表明腹腔内给予OCT对CAPD患者具有治疗效果。