Memoli B, De Nicola L, Libetta C, Scialò A, Pacchiano G, Romano P, Palmieri G, Morabito A, Lauria R, Conte G
Department of Nephrology, University Federico II of Naples, Italy.
Am J Kidney Dis. 1995 Jul;26(1):27-33. doi: 10.1016/0272-6386(95)90149-3.
Recombinant interleukin-2 (rIL-2) is widely used in patients with advanced cancer to enhance killer cell functions. However, the main drawback of rIL-2 therapy is the frequent development of oliguric acute renal failure (ARF), presumably due to a vascular leak syndrome. The aim of this study was to evaluate the effect of low-dose dopamine infusion on this form of ARF. Nine patients with metastatic renal cancer and previous unilateral nephrectomy were treated with a continuous intravenous infusion of rIL-2 (3 x 10(6) Cetus units/m2/d) for 5 days (study A). After 1 week, all the patients repeated the same cycle, but with the addition of a continuous intravenous infusion of dopamine (2 micrograms/min/kg body weight) that was started at the third day of treatment (study B). During study A, all patients showed a progressive (up to 34%) decrease of creatinine clearance. After rIL-2 withdrawal, these alterations persisted and were associated with a reduction in urinary output, sodium urinary excretion, and plasma protein. In study B, dopamine administration after renal function impairment (delta glomerular filtration rate = -44%) led to a prompt improvement of creatinine clearance. Creatinine clearance showed a further significant enhancement after the withdrawal of both drugs, reaching a value within the baseline range on the third day of follow-up. Similarly, the decline in urinary output and sodium excretion during rIL-2 was promptly counteracted by dopamine; in addition, after withdrawal of rIL-2 and dopamine, plasma protein levels were normalized. In conclusion, our data suggest that rIL-2-induced ARF in cancer patients is due to renal hypoperfusion mainly caused by a reduction in oncotic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
重组白细胞介素-2(rIL-2)广泛应用于晚期癌症患者以增强杀伤细胞功能。然而,rIL-2治疗的主要缺点是常发生少尿型急性肾衰竭(ARF),推测是由于血管渗漏综合征所致。本研究的目的是评估小剂量多巴胺输注对这种形式的ARF的影响。9例转移性肾癌且先前已行单侧肾切除术的患者接受连续静脉输注rIL-2(3×10⁶西图斯单位/平方米/天),共5天(研究A)。1周后,所有患者重复相同疗程,但在治疗第3天开始加用连续静脉输注多巴胺(2微克/分钟/千克体重)(研究B)。在研究A期间,所有患者肌酐清除率均呈进行性下降(高达34%)。停用rIL-2后,这些改变持续存在,并伴有尿量、尿钠排泄和血浆蛋白减少。在研究B中,在肾功能损害(肾小球滤过率下降44%)后给予多巴胺导致肌酐清除率迅速改善。停用两种药物后肌酐清除率进一步显著提高,在随访第3天达到基线范围内的值。同样,多巴胺迅速抵消了rIL-2治疗期间尿量和钠排泄的下降;此外,停用rIL-2和多巴胺后,血浆蛋白水平恢复正常。总之,我们的数据表明,癌症患者中rIL-2诱导的ARF是由于主要由胶体渗透压降低引起的肾灌注不足。(摘要截短至250字)