Ifosfamide metabolite chloroacetaldehyde causes Fanconi syndrome in the perfused rat kidney.
Ifosfamide metabolite chloroacetaldehyde causes Fanconi syndrome in the perfused rat kidney.
复制标题
异环磷酰胺代谢物氯乙醛在灌注的大鼠肾脏中引起范可尼综合征。
DOI：
10.1006/taap.1994.1241
复制
发表时间：
1994
影响因子：
3.8
通讯作者：
Springate,JE
中科院分区：
文献类型：
--
作者：
Zamlauski-Tucker,MJ;Morris,ME;Springate,JE
Renal proximal tubule dysfunction has been reported in patients treated with the chemotherapeutic agent ifosfamide. The present study investigated whether ifosfamide or its metabolites acrolein and chloroacetaldehyde would impair function in the isolated perfused rat kidney. Renal function was monitored before and after these chemicals were added to a modified Krebs-Ringer-bicarbonate perfusion medium containing 6.6 g/dl albumin and a mixture of substrates. No functional changes were observed when ifosfamide (470 μM) or acrolein (470 μM) was added to the perfusate. Addition of chloroacetaldehyde (210 μM) resulted in significant decreases in the fractional reabsorption of sodium (from 92 to 32%), glucose (from 97 to 46%), inorganic phosphate (from 88 to 22%), and inorganic sulfate (from 94 to 86%). There were no changes in glomerular filtration rate. PAH clearance also significantly decreased from 4.1 to 0.7 ml/min per gram of kidney weight, indicating impairment of proximal tubule organic acid secretion. This impairment was associated with a significant decline in the extraction ratio for PAH, suggesting abnormal PAH uptake at the basolateral membrane. These results show that chloroacetaldehyde causes generalized renal proximal tubule dysfunction and that it may be the ifosfamide metabolite responsible for nephrotoxic side effects,
