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去铁胺治疗铝中毒透析患者的临床经验。

Clinical experience with desferrioxamine in dialysis patients with aluminium toxicity.

作者信息

McCarthy J T, Milliner D S, Johnson W J

机构信息

Division of Nephrology and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.

出版信息

Q J Med. 1990 Mar;74(275):257-76.

PMID:2117295
Abstract

A desferrioxamine (DFO) infusion test, using a DFO dose of 36.9 +/- 11.2 mg/kg (mean +/- SD), was performed in 50 consecutive dialysis patients undergoing diagnostic bone biopsy. In 30 patients whose bones stained positively for aluminium the serum aluminium level increased by an average of 373 +/- 250.4 ng/ml. The increase in 20 aluminium-negative patients was 231 +/- 179.2 ng/ml (p less than 0.05). Aluminium-positive patients had lower levels of immunoreactive parathyroid hormone (336 +/- 442 muleq/ml) than aluminium-negative patients (1278 +/- 1400 muleq/ml; p less than 0.05). A change in serum aluminium level of greater than 200 ng/ml after the administration of DFO was 73 percent sensitive and 50 percent specific, and had a positive predictive value of 69 percent for detecting positive bone aluminium staining. The combination of a baseline immunoreactive parathyroid hormone level less than 200 muleq/ml and a change in serum aluminium of greater than 200 ng/ml after DFO was 90 percent specific and had a positive predictive value of 85 percent. In the second phase of our study, 28 dialysis patients with aluminium toxicity received long-term therapy (11.0 +/- 4.3 months) with DFO at an average starting dose of 41.7 +/- 17.1 mg/kg, administered once weekly. The four deaths which occurred during this treatment involved the only patients who had advanced dialysis dementia. Seven patients with less severe neurological symptoms responded favourably. Fractures decreased from 1.7 fractures/patient/year to 0.1 fracture/patient/year. Muscular strength and overall functional class were improved or stable in 25 patients; myalgias and arthralgias were also stable or improved in 19 patients. After 5-7 months of treatment, serum aluminium levels decreased from 401 +/- 262 ng/ml to 245 +/- 217 ng/ml (p less than 0.01); erythrocyte mean corpuscular volume increased from 86.3 +/- 10.91 fl to 94.1 +/- 9.23 fl (p less than 0.02); and serum calcium decreased from 10.4 +/- 0.94 mg/dl to 9.9 +/- 0.70 mg/dl (p less than 0.02). Serum immunoreactive parathyroid hormone levels remained stable in 25 patients, but severe hyperparathyroidism developed rapidly in three patients. Eight patients with transfusional iron overload had no change in serum ferritin levels. Iron depletion developed in six patients, with a decrease in serum ferritin from 251 +/- 229.8 micrograms/l to 45 +/- 29.3 micrograms/l, and they required parenteral iron supplementation. Significant side-effects occurring during long-term DFO administration were hypotension (11 patients), gastrointestinal upset (seven patients), porphyria cutaneous tarda-like lesions (three patients), and transient visual disturbance (one patient). There was a decrease in stainable bone aluminium in all nine patients with paired bone biopsy specimens (pre- and post-DFO).(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

对50例接受诊断性骨活检的连续性透析患者进行了去铁胺(DFO)输注试验,DFO剂量为36.9±11.2mg/kg(均值±标准差)。在30例骨铝染色呈阳性的患者中,血清铝水平平均升高373±250.4ng/ml。20例铝染色阴性患者的升高值为231±179.2ng/ml(p<0.05)。铝染色阳性患者的免疫反应性甲状旁腺激素水平(336±442muleq/ml)低于铝染色阴性患者(1278±1400muleq/ml;p<0.05)。DFO给药后血清铝水平变化大于200ng/ml,其敏感性为73%,特异性为50%,检测骨铝染色阳性的阳性预测值为69%。基线免疫反应性甲状旁腺激素水平低于200muleq/ml且DFO给药后血清铝变化大于200ng/ml,其特异性为90%,阳性预测值为85%。在我们研究的第二阶段,28例铝中毒的透析患者接受了DFO长期治疗(11.0±4.3个月),平均起始剂量为41.7±17.1mg/kg,每周给药1次。治疗期间发生的4例死亡病例均为患有晚期透析性痴呆的患者。7例神经症状较轻的患者反应良好。骨折发生率从1.7次/患者/年降至0.1次/患者/年。25例患者的肌肉力量和整体功能分级得到改善或保持稳定;19例患者的肌痛和关节痛也保持稳定或有所改善。治疗5 - 7个月后,血清铝水平从401±262ng/ml降至245±217ng/ml(p<0.01);红细胞平均体积从86.3±10.91fl增至94.1±9.23fl(p<0.02);血清钙从10.4±0.94mg/dl降至9.9±0.70mg/dl(p<0.02)。25例患者的血清免疫反应性甲状旁腺激素水平保持稳定,但3例患者迅速出现严重甲状旁腺功能亢进。8例输血性铁过载患者的血清铁蛋白水平无变化。6例患者出现铁缺乏,血清铁蛋白从251±229.8μg/l降至45±29.3μg/l,他们需要胃肠外补充铁剂。长期给予DFO期间出现的显著副作用包括低血压(11例患者)、胃肠道不适(7例患者)、迟发性皮肤卟啉病样病变(3例患者)和短暂视力障碍(1例患者)。在所有9例有配对骨活检标本(DFO治疗前后)的患者中,可染色骨铝均减少。(摘要截选至400字)

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