成人肾移植受者免疫管理的精准性：平衡类固醇暴露、排斥风险和感染结局

Precision in Immune Management: Balancing Steroid Exposure, Rejection Risk, and Infectious Outcomes in Adult Kidney Transplant Recipients.

作者信息

Koi Avery N, Johnson John C, Engebretsen Trine L, Mujtaba Muhammad A, Lea Alfred Scott, Stevenson Heather L, Kueht Michael L

机构信息

John Sealy School of Medicine, The University of Texas Medical Branch, Galveston, TX 77555-0609, USA.

Department of Surgery, Division of Multiorgan Transplant and Hepatobiliary Surgery, The University of Texas Medical Branch, Galveston, TX 77555-0609, USA.

出版信息

J Pers Med. 2024 Nov 14;14(11):1106. doi: 10.3390/jpm14111106.

DOI:10.3390/jpm14111106

PMID:39590598

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11595447/

Abstract

BACKGROUND/OBJECTIVES: With kidney transplant immunosuppression, physicians must balance preventing rejection with minimizing infection and malignancy risks. Steroids have been a mainstay of these immunosuppression regimens since the early days of kidney transplantation, yet their risks remain debated. Our study looks at the clinical outcomes of patients undergoing early steroid withdrawal (ESW) vs. steroid continuous (SCI) maintenance immunosuppression in adult kidney transplant recipients.

METHODS

A retrospective case-control study, utilizing propensity score-matching, was performed using the US Collaborative Network Database within TriNetX to evaluate renal transplant outcomes at one year in first-time kidney transplant adult patients (>18 years old) who were prescribed an ESW regimen (no steroids after post-transplant day 7 with maintenance tacrolimus [tac] + mycophenolic acid [MMP]/mycophenolate mofetil [MMF]) vs. SCI (tac + MMF/MMP + prednisone). Cohorts were matched on demographics, comorbidities, previously described risk factors for rejection, and induction immunosuppression. Primary outcomes included viral infections, pyelonephritis, and sepsis. Secondary outcomes included renal transplant rejection, death-censored allograft failure (eGFR < 15 mL/min), patient mortality, delayed graft function, and diabetes mellitus.

RESULTS

A total of 2056 patients were in each cohort after matching (mean age: 50.7-51 years, 17.9-20.0% African American, 60-60.6% male.) The SCI cohort had a significantly higher cumulative incidence of composite viremia (18 vs. 28.1%, ESW vs. SCI, < 0.01) driven by CMV, EBV, and BK virus. Post-transplant diabetes mellitus was significantly higher in the SCI cohort (3.21% vs. 5.49%, ESW vs. SCI, < 0.01). Delayed graft function was also higher in the SCI cohort (19.55% vs. 22.79%, ESW vs. SCI, < 0.01). Pyelonephritis (2.3 vs. 4.91%, ESW vs. SCI, < 0.01) and sepsis (2.15 vs. 5.95%, ESW vs. SCI, < 0.01) were higher in the SCI cohort. Rejection rates were similar between ESW and SCI (29 vs. 31%, ESW vs. SCI, = 0.41). There were significantly higher incidences of graft failure (4.9 vs. 9.9%, ESW vs. SCI, < 0.01) and mortality (0.8 vs. 2.1%, ESW vs. SCI, < 0.01) in the SCI cohort.

CONCLUSIONS

This well-matched case-control study suggests that ESW is associated with lower infectious outcomes, mortality, and graft failure without increasing rejection risk, supporting the potential benefits of ESW in kidney transplant patients.

摘要

背景/目的：在肾移植免疫抑制治疗中，医生必须在预防排斥反应与将感染和恶性肿瘤风险降至最低之间取得平衡。自肾移植早期以来，类固醇一直是这些免疫抑制方案的主要组成部分，但其风险仍存在争议。我们的研究观察了成年肾移植受者中接受早期停用类固醇（ESW）与持续使用类固醇（SCI）维持免疫抑制治疗的患者的临床结局。

方法

利用倾向得分匹配法进行一项回顾性病例对照研究，使用TriNetX内的美国协作网络数据库评估首次接受肾移植的成年患者（>18岁）在接受ESW方案（移植后第7天之后不使用类固醇，使用他克莫司[tac] + 霉酚酸[MMP]/霉酚酸酯[MMF]维持治疗）与SCI方案（tac + MMF/MMP + 泼尼松）治疗一年后的肾移植结局。根据人口统计学、合并症、先前描述的排斥反应风险因素和诱导免疫抑制情况对队列进行匹配。主要结局包括病毒感染、肾盂肾炎和脓毒症。次要结局包括肾移植排斥反应、死亡审查的移植物功能衰竭（估算肾小球滤过率[eGFR]<15 mL/分钟）、患者死亡率、移植肾功能延迟恢复和糖尿病。

结果

匹配后每个队列共有2056例患者（平均年龄：50.7 - 51岁，非裔美国人占17.9 - 20.0%，男性占60 - 60.6%）。SCI队列中由巨细胞病毒、EB病毒和BK病毒引起的复合病毒血症累积发生率显著更高（ESW组为18%，SCI组为28.1%，P<0.01）。SCI队列中移植后糖尿病的发生率也显著更高（ESW组为3.21%，SCI组为5.49%，P<0.01）。SCI队列中移植肾功能延迟恢复的发生率也更高（ESW组为19.55%，SCI组为22.79%，P<0.01）。SCI队列中肾盂肾炎（ESW组为2.3%，SCI组为4.91%，P<0.01）和脓毒症（ESW组为2.15%，SCI组为5.95%，P<0.01）的发生率更高。ESW组和SCI组的排斥反应发生率相似（ESW组为29%，SCI组为31%，P = 0.41）。SCI队列中移植物功能衰竭（ESW组为4.9%，SCI组为9.9%，P<0.01）和死亡率（ESW组为0.8%，SCI组为2.1%，P<0.01）的发生率显著更高。