比较动力学的尿毒症毒素p-cresol与肌酐在老鼠和肾功能衰竭。

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Lesaffer G迪斯美特R D 'Heuvaert T, Belpaire调频,Lameire N, Vanholder R

比较动力学的尿毒症毒素p-cresol与肌酐在老鼠和肾功能衰竭。

肾脏Int。2003年10月,64 (4):1365 - 73。doi: 10.1046 / j.1523-1755.2003.00228.x。

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12969155 (在PubMed

]

文摘

背景:p-cresol,广泛代谢成p-cresylglucuronide鼠,与几个生化和生理改变目前的血液透析尿毒症,而不是删除充分策略。其体内动力学行为的知识可能有助于改善当前删除策略。方法:我们研究的动力学行为通过静脉注射p-cresol(10毫克/公斤)在大鼠与正常和肾功能下降,并比较结果与获得肌酐在类似条件下(60毫克/公斤)。肾功能衰竭得到5/6肾切除术。p-cresol和p-cresylglucuronide分析了用反相高效液相色谱法(rp)。之间的关系p-cresylglucuronide峰高和底层的p-cresol决心与beta-glucuronidase葡糖苷酸水解后。我们计算尿排泄与没有考虑p-cresylglucuronide p-cresol。此外,总、肾和non-renal间隙,半衰期,和体积p-cresol分布计算。结果:在4小时内,p-cresol血清浓度显示只有一个最小的老鼠与降低肾功能下降(t1/2 = 11.7 + / - 0.4小时),而与正常大鼠肾功能(t1/2 = 1.4 + / - 0.7小时)。类似的观察是为p-cresylglucuronide。 In rats with normal renal function, 21.0 +/- 10.0% of the injected p-cresol was excreted in urine as p-cresol and 60.7 +/- 25.0% as p-cresylglucuronide; in rats with renal failure, the respective amounts were 6.7 +/- 7.5% and 32.0 +/- 25.3% (P < 0.05 vs. normal renal function) (total recovery 81.81 +/- 31.07% vs. 38.50 +/- 32.09%, P < 0.05). The volume of distribution of p-cresol was approximately 4 times larger than that of creatinine, but was not significantly affected by renal failure. Not only renal, but also non-renal and total clearance, were much lower in rats with decreased renal function. CONCLUSION: The present data sheds a light on the kinetic behavior of p-cresol in uremic patients; the large volume of distribution, especially, might explain the inadequate dialytic removal of p-cresol. In addition, a substantial amount of p-cresol is removed by metabolism, and both renal and non-renal clearance are disturbed in uremia.

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