Caspofungin for preventing fungal infection after kidney transplantation using donation after cardiac death donors: a prospective controlled trial

doi:10.3969/j.issn.2095-4344.2017.32.018

Abstract

Abstract:

BACKGROUND: Caspofungin, a novel echinocandins systemic antifungal agent, has been shown to exert broad-spectrum antibacterial effect on deep fungal infections, which is superior to or equivalent with the role of amphotericin B, but there is no report on its application for preventing fungal infection after renal transplantation.
OBJECTIVE: To analyze the difference in high risk factors of fungal infection after kidney transplantation using donation after cardiac death donors and living-related donor kidney transplantations, and to explore the feasibility and safety of caspofungin to prevent fungal infection after kidney transplantation using donation after cardiac death donors.
METHODS: This was a prospective, single-center, controlled trial finished at the Department of Kidney Transplantation, the First Affiliated Hospital of Zhengzhou University, Henan Province, China. Totally 188 patients undergoing primary kidney transplantation without history of fungal infection and use of antifungal drugs between January 2012 and August 2013 were enrolled, including kidney transplantation with donation after cardiac death donors (n=102, trail group), and kidney transplantation with living-related donors (n=86, control group). The CYP3A5 genotype was determined preoperatively. All patients received tacrolimus+mycophenolate mofetil+prednisone triple immunosuppression after transplantation. The trial group was subjected to caspofungin therapy for 2 weeks. The risk factors for fungal infection in the two groups were compared, and the effects of caspofungin on the tacrolimus concentration, tacrolimus concentration/dose were detected in the recipients with same CYP3A5 genotype recipients at 1 and 2 weeks, and 1, 3 and 6 months postoperatively. The liver and kidney function, adverse events and fungal infections were recorded at different time points. This trial was registered with the Chinese Clinial Trial Registry (Regitration number: ChiCTR-OON-17013342).
RESULTS AND CONCLUSION: The survival rate of patient/kidney was 98.4% and 97.3% respectively, 97 cases in the trial group and 86 controls competed 6-month follow-up. Preoperative hemodialysis time, hemoglobin value, cold ischemia time, warm ischemia time, intraoperative blood transfusion volume, time of central venous catheter kept in situ, methylprednisolone usage, ATG usage, serum creatinine reduced level at 1 week, thrombocytopenia and duration of postoperative body temperature > 38 ℃ were the risk factors for fungal infection in the trail group relative to the control group. The fungal infection rate in the trial and control groups was 0% and 2.3%, respectively, at 6 months of follow-up. The serum creatinine level in the trail group was significantly higher than that in the control group at 1 month postoperatively (P < 0.05), and the level showed no significant difference between two groups at other time points (P > 0.05). After 2 weeks of caspofungin treatment, the concentrations of tacrolimus and tacrolimus concentration/dosage did not differ significantly in different CYP3A5 genotype recipients (P > 0.05). Caspofungin might induce some adverse reactions, especially electrolyte disturbance with an incidence of 21.6%, but there was no significant difference between two groups (P > 0.05). These findings imply that kidney transplantation using donation after cardiac death donors presents with various risk factors for fungal infection compared with living-related donor kidney transplantation. Furthermore, caspofungin is effective and safe for preventing fungal infection and has no effect on tacrolimus concentration; therefore, it can be used as a new anti-fungal agent after kidney transplantation.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Key words: Kidney Transplantation, Anti-fungal Agents, Echinocandins, Tissue Engineering

CLC Number:

R318

Shang Wen-jun, Wang Zhi-gang, Suo Jing-jun, Li Jin-feng, Pang Xin-lu, Feng Yong-hua, Liu Lei, Xie Hong-chang,Feng Gui-wen. Caspofungin for preventing fungal infection after kidney transplantation using donation after cardiac death donors: a prospective controlled trial[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(32): 5189-5196.

Figures/Tables 3

2.1 试验状态试验已经完成，数据已经收集完毕。目前正在进行临床试验的补注册。以下是试验结果。 2.2 一般情况受者随访6个月人/肾存活率分别为98.4%，97.3%。试验组102例，1例术后40 d发生移植动脉栓塞而死亡，1例术后8 d因急性心肌梗死而猝死，1例术后1个月因肝囊肿治疗无效而死亡，经穿刺脓液培养未发现真菌；发生急性排斥反应4例，2例经甲强龙1.0-1.5 g冲击后逆转，2例术后1周因移植肾破裂而切除；发生移植肾功能延迟恢复2例，2个月后肾功能恢复；至随访6个月试验组共入组97例。对照组86例全部获得随访，发生急性排斥反应3例，经加强龙1.0-1.5 g冲击后均逆转；发生移植肾功能延迟恢复1例，1个月后肾功能恢复。患者详细基线资料详见表1。 2.3 肾移植术后真菌感染高危因素在众多肾移植术后真菌感染高危因素中，下列因素试验组与对照组相比差别显著(P < 0.05)：术前透析时间、血红蛋白值、冷缺血时间、热缺血时间、术中输血量、中心静脉导管留置时间、甲强龙用量、ATG用量、1周时血肌酐下降幅度、血小板减少症和术后体温> 38 ℃持续时间，即试验组相对对照组更易引起术后真菌感染，详见表2。 2.4 肾移植术后感染情况试验组术后发生感染18例(18.6%)，其中肺部感染17例，泌尿系感染1例，合并CMV感染2例，未发现真菌感染者；对照组术后发生肺部感染15例(17.4%)，其中病原学确诊合并白色念珠菌感染2例，合并CMV感染1例；两组患者给予抗生素和(或)抗病毒药物，确诊真菌感染者给予卡泊芬净治疗后均治愈。两组随访6个月，真菌感染率分别为0%、2.3%。 2.5 两组肾移植术后血肌酐值比较术后1周试验组血肌酐高于对照组(P < 0.05)，随后各随访时间点两组血肌酐值差异无显著性意义(P > 0.05)。详见表3、图2。 2.6 卡泊芬净对不同CYP3A5基因型受者他克莫司谷浓度和和他克莫司谷浓度/剂量比值影响各随访时间点比较均无差异(P > 0.05)。详见表4、5。 2.7 卡泊芬净安全性统计术后可能与卡泊芬净有关的不良反应，以电解质紊乱发生率最高，为21.6%；但试验组与对照组比较差异均无显著性意义(P > 0.05)，具体结果见表6。"

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