腹泻对肾移植受者他可莫司血药浓度的影响

Effect of diarrhea on tacrolimus blood trough levels in kidney transplantation recipients

目的:观察腹泻对肾移植受者他克莫司谷浓度的影响,并探讨其发生的可能原因和机制。方法:观察了肾移植术后出现腹泻的患者27例,在他克莫司和环孢素治疗组中分别有20例和7例。观察了围腹泻期药物剂量及谷浓度变化,并进行了与腹泻相关病原学检查。结果:在腹泻期间分别有15例(75%)和2例(28.6%)患者他克莫司和环孢素谷浓度明显升高。通过抗感染、减低霉酚酸酯剂量及止泻等综合治疗,腹泻治愈,他克莫司谷浓度在腹泻愈后3～17 d内下降至治疗范围。结论:腹泻是引起他克莫司谷浓度升高的重要因素。腹泻期间应适当减低他克莫司剂量和密切监测他克莫司谷浓度变化。

Objective：To observe the effect of diarrhea on tacrolimus （Tac） trough levels in renal transplant reciepients, and to analyze possible factors and mechanisms contributed to the episode. Methodology：Twenty-seven cases with diarrhea were observed after renal transplantation. 20 cases were received triple immunosuppressive protocols in Tac incombination with myeophenolate mofetil （MMF） and prednisone, and 7 cases were in cyclosporine ineombination with MMF and prednisone, respectively. We retrospectively reviewed changes of Tac and eyelosporine trough levels before, during and after diarrhea, respectively. Moreover, some etiological laboratory tests related to diarrhea, such as feces routine test, feces smear and rotavirus immunodetection in feces specimen, were performed. Results：Diarrhea mainly resulted from MMF-induced and gastroenteritis after transplantation. The Tac trough levels were significantly elevated during diarrhea in 15 （ 75% ） recipients, whereas there were only 2 （ 28. 6% ） with elevated cyclosporine trough levels in the observed patients, compared with therapeutical ranges before diarrhea episode. The combined therapy, including treatment of antidiarrhoeal drug, reducing MMF doses and administration of antibiotics, had a good efficacy on diarrhea. The Tae trough levels were returned to target range between 3 - 17 days since the patients stopping diarrhea. The cyclosporine trough levels decreased below therapeutical ranges on day 2 after reducing dose. All of the patients have not any a episode of acute rejection during observation. Effect of diarrhea on levels of serum creatinine was not found in this study. Conclusion： Diarrhea following kidney transplantation could significantly result in elevated Tac but not cyclosporine trough levels. Until fully recovery from diarrhea, Tac trough levels were gradually returned to therapeutical range. Disruption of the intestinal epithelial barrier cells and non-specific colonic absorption of Tac may lead to extreme elevations in blood Tac levels. In order to prevent any a possible toxical effect of high blood Tac concentration during diahhea, antibiotic therapy to diarrhea, reduction of MMF dose, and modulation of Tac dosage are necessary.