Zheng Xiang, Zhang Weijie, Zhou Hua, Cao Ronghua, Shou Zhangfei, Zhang Shuwei, Cheng Ying, Chen Xuchun, Ding Chenguang, Tang Zuofu, Li Ning, Shi Shaohua, Zhou Qiang, Chen Qiuyuan, Chen Gang, Chen Zheng, Zhou Peijun, Hu Xiaopeng, Zhang Xiaodong, Na Ning, Wang Wei
Department of Urology, Capital Medical University Beijing Chaoyang Hospital, Beijing 100020, China.
Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430032, China.
Chin Med J (Engl). 2022 Jul 25;135(13):1597-603. doi: 10.1097/CM9.0000000000001866.
The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.
Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients' vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/ cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.
The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.
Chinese Clinical Trial Registry, ChiCTR1800017277.
肾移植后常用的基于钙调神经磷酸酶抑制剂（CNI）的免疫维持方案极大地提高了移植后早期移植物存活率；然而，移植物的长期预后并未得到显著改善。CNI药物的肾毒性是移植物长期预后不良的主要危险因素之一。西罗莫司（SRL）作为一种免疫抑制剂已在临床实践中应用20多年，并且已发现其对移植物无肾毒性作用。目前，肾移植后SRL应用的方案和时机各不相同，且临床数据稀缺。多中心前瞻性随机对照研究尤为罕见。本研究旨在探讨早期转换为低剂量CNI联合SRL对肾移植长期预后的影响。
在中国多个移植中心接受肾移植后四周标准方案（CNI+霉酚酸（MPA）+糖皮质激素）治疗的患者将纳入本研究。术后第5周，实验组患者将额外给予SRL，减少CNI药物剂量，停用MPA药物，并维持糖皮质激素治疗。此外，对照组患者将接受维持性标准治疗。记录患者在基线以及转换后第12、24、36、48、72和104周时的生命体征、血常规、尿常规、血液生化、血清肌酐、BK病毒（BKV）/巨细胞病毒（CMV）以及CNI药物和SRL的谷浓度。计算患者生存率、移植物生存率和估计肾小球滤过率，并记录伴随用药情况和不良事件。
研究数据将用于评估肾移植患者早期转换为低剂量CNIs联合SRL的疗效和安全性。
中国临床试验注册中心，ChiCTR1800017277。
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