Stewart D J, Mikhael N Z, Nanji A A, Nair R C, Kacew S, Howard K, Hirte W, Maroun J A
J Clin Oncol. 1985 Sep;3(9):1251-6. doi: 10.1200/JCO.1985.3.9.1251.
Autopsy tissues were obtained from 30 patients who had received cisplatin antemortem; the tissues were assayed for platinum by flameless atomic absorption spectrometry. Patients with antemortem evidence of renal toxicity had higher renal cortical platinum concentrations than did patients without evidence of kidney damage. In addition, patients with nephrotoxicity were more likely than patients without toxicity to have renal cortical platinum concentrations that were higher than renal medullary platinum concentrations. Overall, the two variables most closely associated with an increase in serum creatinine with treatment were renal cortical platinum concentration (P less than .02) and cumulative dose of cisplatin (P less than .05). These two variables were important independently of one another. Renal cortex platinum concentrations correlated inversely with time from last treatment until death, whereas hepatic platinum concentrations did not. In contrast, hepatic platinum concentrations correlated with dose of cisplatin while renal platinum concentrations did not. Our results suggest the following: (1) cisplatin-induced renal toxicity is tissue-platinum-concentration dependent and cisplatin-dose dependent; and (2) cisplatin may be handled differently at the molecular level in liver and kidney.
尸检组织取自30例生前接受过顺铂治疗的患者；采用无火焰原子吸收光谱法对组织中的铂进行检测。有生前肾毒性证据的患者，其肾皮质铂浓度高于无肾损伤证据的患者。此外，有肾毒性的患者比无毒性的患者更有可能出现肾皮质铂浓度高于肾髓质铂浓度的情况。总体而言，与治疗后血清肌酐升高最密切相关的两个变量是肾皮质铂浓度（P<0.02）和顺铂累积剂量（P<0.05）。这两个变量彼此独立且都很重要。肾皮质铂浓度与最后一次治疗至死亡的时间呈负相关，而肝铂浓度则不然。相反，肝铂浓度与顺铂剂量相关，而肾铂浓度则与剂量无关。我们的结果表明：（1）顺铂诱导的肾毒性取决于组织铂浓度和顺铂剂量；（2）顺铂在肝脏和肾脏的分子水平上可能有不同的处理方式。
