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重组白细胞介素-2持续输注对儿童肾脏的影响。

Renal effects of continuous infusion of recombinant interleukin-2 in children.

作者信息

Cochat P, Floret D, Bouffet E, Francks C R, Favrot M C, Philip T, David L

机构信息

Paediatric Renal Unit, E. Herriot Hospital, Lyon, France.

出版信息

Pediatr Nephrol. 1991 Jan;5(1):33-7. doi: 10.1007/BF00852838.

DOI:10.1007/BF00852838
PMID:2025534
Abstract

Recombinant interleukin-2 (rIL-2) is a new promising treatment for cancer, but is associated with severe renal toxicity. This study is the first to analyse the renal effects of rIL-2 in children. Twenty-one cycles of continuous rIL-2 infusion were studied in 15 patients; mean age was 6.9 years and average weight 18.9 kg. Interstitial fluid retention and oliguria (baseline, 1.7 ml/kg per hour; nadir, 0.5 mg/kg per hour) were associated with hypotension (baseline, 101/56 mm Hg; nadir, 85/43 mm Hg) and decreased intravascular volume (plasma renin activity increased x 10). Weight gain (+7.9%) was observed in 13 cycles whereas weight loss (-6.3%) was shown in 8 cycles because of digestive and cutaneous losses, mainly in the youngest patients. This prerenal azotaemia was characterized by a decrease in creatinine clearance (from 101 to 36 ml/min per 1.73 m2) and a low fractional excretion of sodium (FENa) (from 0.70% to 0.09%). Hypotension and hypovolaemia needed vascular filling (n = 12), dopamine (n = 7) and interruption of rIL-2 (n = 2). Most abnormalities occurred as early as day 2 of therapy and were always reversible after a short period with sodium leakage (diuresis = 2.2 ml/kg per hour, FENa = 2.01%). Hypophosphataemia was associated with low urinary excretion of phosphorus, suggesting an increased uptake of inorganic phosphorus by rapidly proliferating lymphoid cells.

摘要

重组白细胞介素-2(rIL-2)是一种新的有前景的癌症治疗药物,但与严重的肾毒性相关。本研究首次分析了rIL-2对儿童肾脏的影响。对15例患者进行了21个周期的rIL-2持续输注研究;平均年龄为6.9岁,平均体重为18.9千克。间质液潴留和少尿(基线值为每小时1.7毫升/千克;最低点为每小时0.5毫克/千克)与低血压(基线值为101/56毫米汞柱;最低点为85/43毫米汞柱)和血管内容量减少(血浆肾素活性增加10倍)相关。13个周期观察到体重增加(+7.9%),而8个周期出现体重减轻(-6.3%),原因是消化和皮肤丢失,主要发生在最年幼的患者中。这种肾前性氮质血症的特征是肌酐清除率降低(从每1.73平方米101降至36毫升/分钟)和低钠排泄分数(FENa)(从0.70%降至0.09%)。低血压和血容量不足需要进行血管补液(n = 12)、使用多巴胺(n = 7)以及中断rIL-2治疗(n = 2)。大多数异常情况最早在治疗第2天出现,且在短时间内钠排泄增加(尿量 = 每小时2.2毫升/千克,FENa = 2.01%)后总是可逆的。低磷血症与尿磷排泄减少相关,提示快速增殖的淋巴细胞对无机磷的摄取增加。

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引用本文的文献

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J Cancer Res Clin Oncol. 1993;119(12):745-55. doi: 10.1007/BF01195347.
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Clinical toxicity of interleukin-2.

本文引用的文献

1
Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer.对转移性癌症患者进行自体淋巴因子激活的杀伤细胞和重组白细胞介素-2全身给药的观察。
N Engl J Med. 1985 Dec 5;313(23):1485-92. doi: 10.1056/NEJM198512053132327.
2
Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin 2.重组白细胞介素-2全身给药介导的血管内液体外渗
J Immunol. 1986 Sep 1;137(5):1735-42.
3
Effects of interleukin-2 on renal function in patients receiving immunotherapy for advanced cancer.
白细胞介素-2的临床毒性
Drug Saf. 1992 Nov-Dec;7(6):417-33. doi: 10.2165/00002018-199207060-00004.
白细胞介素-2对接受晚期癌症免疫治疗患者肾功能的影响。
Ann Intern Med. 1987 Jun;106(6):817-22. doi: 10.7326/0003-4819-106-6-817.
4
Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer.持续输注重组白细胞介素-2在晚期癌症过继性免疫治疗中的应用
N Engl J Med. 1987 Apr 9;316(15):898-905. doi: 10.1056/NEJM198704093161502.
5
A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone.关于使用淋巴因子激活的杀伤细胞和白细胞介素-2或单独使用高剂量白细胞介素-2治疗157例晚期癌症患者的进展报告。
N Engl J Med. 1987 Apr 9;316(15):889-97. doi: 10.1056/NEJM198704093161501.
6
Reduction of toxicity of interleukin-2 and lymphokine-activated killer cells in humans by the administration of corticosteroids.通过给予皮质类固醇降低白细胞介素-2和淋巴因子激活的杀伤细胞在人体内的毒性。
J Clin Oncol. 1987 Mar;5(3):496-503. doi: 10.1200/JCO.1987.5.3.496.
7
Actions of tumor necrosis factor on cultured vascular endothelial cells: morphologic modulation, growth inhibition, and cytotoxicity.肿瘤坏死因子对培养的血管内皮细胞的作用:形态学调节、生长抑制及细胞毒性。
J Natl Cancer Inst. 1986 Jun;76(6):1113-21.
8
Renal physiology of the prostaglandins and the effects of nonsteroidal anti-inflammatory agents on the kidney.前列腺素的肾脏生理学以及非甾体抗炎药对肾脏的影响。
Am J Nephrol. 1987;7(5):408-18. doi: 10.1159/000167510.
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Multiple organ failure during interleukin-2 administration and LAK cells infusion.在给予白细胞介素-2和输注淋巴因子激活的杀伤细胞期间出现多器官功能衰竭。
Intensive Care Med. 1988;14(6):666-7. doi: 10.1007/BF00256776.
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Metabolic and renal effects of interleukin-2 immunotherapy for metastatic cancer.白细胞介素-2免疫疗法对转移性癌症的代谢和肾脏影响。
Clin Nephrol. 1988 Sep;30(3):141-5.