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癌症化疗引起的肾毒性,特别强调顺铂毒性。

Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity.

作者信息

Ries F, Klastersky J

出版信息

Am J Kidney Dis. 1986 Nov;8(5):368-79. doi: 10.1016/s0272-6386(86)80112-3.

Abstract

Renal failure in cancer patients is a common problem in oncology; this complication is frequently multifactorial in origin. Several antineoplastic agents are potentially nephrotoxic; previous renal impairment as well as combinations with other nephrotoxic drugs may increase the risk of nephrotoxicity during administration of chemotherapy. Methotrexate-related renal damage most frequently occurs with high-dose therapy and can be avoided by forced alkaline diuresis and administration of folinic acid. Renal dysfunction secondary to semustine (CH3-CCNU) is clearly related to cumulative doses in excess to 1,200 mg/m2; the onset may be delayed and renal failure progress despite drug discontinuation. Streptozotocin is also nephrotoxic and may cause proteinuria and renal tubular acidosis; progressive renal failure can be predicted by a close monitoring of proteinuria and prevented by drug discontinuance. Mitomycin-associated renal failure frequently presents with signs of microangiopathic hemolytic anemia; renal failure is usually delayed but occasionally, it may be rapidly progressive despite drug discontinuance. Cisplatin nephrotoxicity is clearly dose-related and used to be considered dose limiting. Renal insufficiency can be prevented by hydration and forced diuresis; in addition, hyperhydration with mannitol-induced saline diuresis may allow administration of high doses and thus circumvent the dose-limiting effect of cisplatin-induced renal toxicity. Cisplatin-induced renal magnesium wasting occurs frequently and should be supplemented. Other approaches to reduce cisplatin nephrotoxicity are currently under investigation and are discussed.

摘要

癌症患者的肾衰竭是肿瘤学中的常见问题;这种并发症的病因通常是多因素的。几种抗肿瘤药物具有潜在的肾毒性;既往肾功能损害以及与其他肾毒性药物联合使用可能会增加化疗期间发生肾毒性的风险。甲氨蝶呤相关的肾损害最常发生于高剂量治疗时,可通过强制碱性利尿和给予亚叶酸来避免。司莫司汀(环己亚硝脲)继发的肾功能障碍显然与累积剂量超过1200mg/m²有关;发病可能延迟,即使停药肾衰竭仍会进展。链脲佐菌素也具有肾毒性,可能导致蛋白尿和肾小管酸中毒;通过密切监测蛋白尿可预测进行性肾衰竭,并通过停药来预防。丝裂霉素相关的肾衰竭常伴有微血管病性溶血性贫血的体征;肾衰竭通常延迟出现,但偶尔即使停药也可能迅速进展。顺铂肾毒性显然与剂量相关,过去曾被认为是剂量限制性的。通过水化和强制利尿可预防肾功能不全;此外,用甘露醇诱导的盐水利尿进行过度水化可能允许给予高剂量,从而规避顺铂诱导的肾毒性的剂量限制作用。顺铂诱导的肾镁流失经常发生,应予以补充。目前正在研究并讨论其他降低顺铂肾毒性的方法。

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