Mărunţelu Ion, Nistor Claudiu Eduard, Cristea Bogdan Mihai, Rotarescu Corina Andreea, Caragea Andreea Mirela, Tizu Maria, Constantinescu Ileana
Center for Immunogenetics and Virology, Fundeni Clinical Institute, Bucharest, Romania.
"Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania.
Ann Transplant. 2022 Aug 12;27:e937267. doi: 10.12659/AOT.937267.
BACKGROUND Kidney transplantation is the most recommended treatment in chronic kidney disease. The recipient's immune system reacts to a kidney graft as to an alloantigen by producing antibodies (anti-human leukocyte antigens [HLAs]). Although immunosuppressive therapy is used to overcome this problem, the long-term survival of a kidney graft after 5 years remains low. This retrospective study from a single center in Romania of 347 renal transplant patients treated with tacrolimus, mycophenolate, and steroids aimed to evaluate the association between anti-HLA antibodies and 5-year graft survival. MATERIAL AND METHODS Anti-HLA antibodies were screened and identified using the Luminex method, while tacrolimus levels were monitored using the chemiluminescent assay. RESULTS Twenty-seven patients had pre-existing anti-HLA antibodies, while 320 patients did not. Of the 320 patients, 15% developed anti-HLA antibodies following kidney transplantation. The intrapatient minimum blood level of tacrolimus (cut-off value: 4.6 ng/mL) after transplantation was significantly associated with the risk of de novo anti-HLA antibodies (P<0.001). In patients with or without de novo anti-HLA antibodies, the 5-year allograft survival rate was 77.1% vs 90.8% (P=0.004). After Bonferroni correction, donor age (P=0.001), and donor type (P<0.0001) were statistically associated with the risk of allograft rejection. CONCLUSIONS This study showed that anti-HLA antibodies at 5 years after kidney transplantation were significantly associated with graft failure. The findings support previous studies and indicate that monitoring of anti-HLA antibodies should be considered in patients with renal transplant.
肾移植是慢性肾脏病最推荐的治疗方法。受者的免疫系统会将肾移植视为同种异体抗原，从而产生抗体（抗人类白细胞抗原 [HLA]）。尽管使用免疫抑制疗法来克服这一问题，但肾移植5年后的长期存活率仍然很低。这项来自罗马尼亚单一中心的回顾性研究，对347例接受他克莫司、霉酚酸酯和类固醇治疗的肾移植患者进行了研究，旨在评估抗HLA抗体与5年移植肾存活率之间的关联。
使用Luminex方法筛选和鉴定抗HLA抗体，同时使用化学发光法监测他克莫司水平。
27例患者术前就存在抗HLA抗体，而320例患者没有。在这320例患者中，15%在肾移植后产生了抗HLA抗体。移植后患者体内他克莫司的最低血药浓度（临界值：4.6 ng/mL）与新发抗HLA抗体的风险显著相关（P<0.001）。在有或没有新发抗HLA抗体的患者中，5年移植肾存活率分别为77.1%和90.8%（P=0.004）。经Bonferroni校正后，供体年龄（P=0.001）和供体类型（P<0.0001）与移植肾排斥风险在统计学上相关。
本研究表明，肾移植后5年的抗HLA抗体与移植肾失败显著相关。这些发现支持了先前的研究，并表明肾移植患者应考虑监测抗HLA抗体。
