College of Medicine, University of Cincinnati, Cincinnati, Ohio.
Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada.
JAMA Surg. 2021 Apr 1;156(4):307-314. doi: 10.1001/jamasurg.2020.6929.
The complications of corticosteroids make the inclusion of these drugs in immunosuppressive protocols for kidney transplant patients undesirable. However, cessation of corticosteroids is associated with a higher risk of short-term rejection, and the long-term outcomes of patients withdrawn from corticosteroids remain uncertain.
To compare long-term kidney transplant outcomes of patients randomized to continue or withdraw corticosteroids.
DESIGN, SETTING, AND PARTICIPANTS: This prospective multicenter randomized double-blind placebo-controlled trial was conducted between November 1999 and December 2002 with linkage to a mandatory national registry with validated outcome ascertainment until June 8, 2018. The study included 28 kidney transplant centers in the United States, including 386 low- to moderate-immune risk adult recipients of a living or deceased donor kidney transplant without delayed graft function or short-term rejection in the first week after transplant. Analyses were intention to treat. Analysis began September 2018 and ended June 2019.
Patients were randomized to receive tacrolimus and mycophenolate mofetil with or without corticosteroids 7 days after transplant.
Kidney allograft failure from any cause including death and allograft failure censored for patient death defined by the requirement for long-term dialysis or repeat transplant.
Of 385 patients, 191 were assigned to withdraw from corticosteroids (mean [SD] age, 46.5 [12.1] years), and 194 patients were assigned to continued corticosteroids (mean [SD] age, 46.3 [12.6] years). The median (interquartile range) follow-up time was 15.8 (12.0-16.3) years after transplant. The adjusted hazard ratios of allograft failure from any cause including death was 0.83 (95% CI, 0.62-1.10; P = .19) and for allograft failure censored for patient death was 0.78 (95% CI, 0.52-1.19; P = .25) and did not differ between the patients assigned to withdraw from corticosteroids vs assigned to continued corticosteroids. Results were consistent in a per-protocol analysis among 223 patients who continued the trial-assigned treatment of corticosteroid withdrawal (n = 114) or corticosteroids (n = 109) through at least 5 years after transplant. The outcomes of trial participants in either treatment group did not differ from similarly treated contemporary registry patients who met trial eligibility criteria and were treated with the same immunosuppressive drugs.
Long-term corticosteroids may not be necessary as part of a calcineurin-based multiple drug immunosuppressive regimen in low- to moderate-immune risk kidney transplant recipients.
皮质类固醇的并发症使得将这些药物纳入肾移植患者的免疫抑制方案中变得不理想。然而，停止使用皮质类固醇会增加短期排斥反应的风险，并且停用皮质类固醇的患者的长期预后仍不确定。
比较继续或停用皮质类固醇的肾移植患者的长期肾脏移植结局。
设计、地点和参与者：这是一项前瞻性多中心随机双盲安慰剂对照试验，于 1999 年 11 月至 2002 年 12 月进行，并与强制性国家注册中心进行了链接，该注册中心对验证后的结局进行了确认，直到 2018 年 6 月 8 日。该研究包括美国 28 个肾移植中心，包括 386 名低至中度免疫风险的成人活体或已故供体肾移植受者，无移植后第 1 周延迟移植物功能或短期排斥反应。分析采用意向治疗。分析于 2018 年 9 月开始，2019 年 6 月结束。
患者在移植后 7 天随机接受他克莫司和霉酚酸酯加或不加皮质类固醇。
任何原因导致的移植肾失功，包括死亡和因长期透析或重复移植而需要长期透析或重复移植的患者定义的移植肾失功。
在 385 名患者中，191 名被分配停用皮质类固醇（平均[SD]年龄，46.5[12.1]岁），194 名被分配继续使用皮质类固醇（平均[SD]年龄，46.3[12.6]岁）。移植后中位（四分位距）随访时间为 15.8（12.0-16.3）年。所有原因导致的移植物失功（包括死亡）的调整后风险比为 0.83（95%CI，0.62-1.10；P=0.19），因患者死亡而对移植物失功进行校正的风险比为 0.78（95%CI，0.52-1.19；P=0.25），两组间无差异。在 223 名继续接受试验分配的皮质类固醇停药（n=114）或皮质类固醇（n=109）治疗至少 5 年的患者中进行方案意向治疗分析时，结果一致。在接受同样治疗的当代注册患者中，试验参与者的结局与符合试验入选标准且接受相同免疫抑制药物治疗的患者相似。
在低至中度免疫风险的肾移植受者中，长期皮质类固醇可能不是钙调神经磷酸酶为基础的多种药物免疫抑制方案的必要组成部分。
