Kidney Transplant Recipients

肾移植受者
  • 文章类型: Journal Article
    背景:Roxadustat,缺氧诱导因子脯氨酸酰羟化酶结构域酶的口服抑制剂,已被批准用于治疗肾性贫血。然而,缺乏对早期移植后贫血(PTA)的肾移植受者(KTRs)的药代动力学研究。因此,本研究的目的是阐明罗沙司他在早期PTAKTRs中的药代动力学特征,并优化给药方案.
    方法:基于从52个中国人KTR收集的72小时全浓度-时间曲线进行群体药代动力学(PopPK)分析。使用逐步协变量建模评估影响暴露的协变量。进行蒙特卡罗模拟以推荐具有不同协变量水平的患者的给药方案。
    结果:PopPK分析表明,浓度-时间数据可以通过两室模型充分描述。体重(BW)和直接胆红素(DBIL)水平显着影响罗沙司他的表观清除率。基于建立的模型和蒙特卡洛模拟法估计的roxadustat暴露量,在不同的BW和DBIL水平下,针对早期PTA的KTRs制定了推荐的给药方案.Roxadustat每周三次100mg适用于大多数KTR,DBIL水平约为3μmol/L,BW在50至75kg之间。所需剂量可能需要随着较高的BW和较低的DBIL水平而增加,而随着较低的BW和较高的DBIL水平而降低。
    结论:这是罗沙司他在早期PTA的KTRs中的第一个PopPK分析,为优化给药方案提供了研究依据。
    BACKGROUND: Roxadustat, an oral inhibitor of hypoxia-inducible factor prolyl hydroxylase domain enzymes, has been approved for the treatment of renal anemia. However, there is a lack of study on its pharmacokinetics in kidney transplant recipients (KTRs) with early posttransplant anemia (PTA). Therefore, the aim of this study is to elucidate the pharmacokinetic characteristics of roxadustat in KTRs with early PTA and optimize the dosing regimen.
    METHODS: A population pharmacokinetic (PopPK) analysis was performed based on 72-hour full concentration-time profiles collected from 52 Chinese KTRs. Covariates influencing exposure were assessed using stepwise covariate modelling. Monte Carlo simulations were conducted to recommend the dosing regimen for patients with different levels of covariates.
    RESULTS: PopPK analysis showed that the concentration-time data can be fully described by a two-compartment model. Body weight (BW) and direct bilirubin (DBIL) levels significant affected the apparent clearance of roxadustat. Based on the established model and the estimated exposures of roxadustat by Monte Carlo simulations, a recommended dosing regimen for KTRs with early PTA at varying BW and DBIL levels were developed. Roxadustat at 100 mg three times weekly were suitable for the majority of KTRs with a DBIL level around 3 μmol/L and BW between 50 and 75 kg. The required dose may need to be increased with higher BW and lower DBIL levels, while decreased with lower BW and higher DBIL levels.
    CONCLUSIONS: It was the first PopPK analysis of roxadustat in KTRs with early PTA, which provide a research basis for optimizing the dosing regimen.
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    文章类型: Journal Article
    管理移植后护理对肾移植受者构成挑战,通常是由于食物负担能力和参与体育活动的能力。这项研究探讨了接受者对护理的自我管理以及健康的社会决定因素对体育锻炼和饮食的影响。单中心,横断面研究通过MyChart(综合医疗保健信息系统患者门户)招募了26名参与者,以完成86个问题的调查。参与者的平均年龄为61岁,85%拥有副学士学位或更高学位。体重指数与避免高热量食物呈负相关;年龄和教育程度与体育锻炼呈正相关。肾移植受者表现出有限的运动和频繁的高热量食物消耗。有针对性的干预措施,特别是促进有规律的身体活动,对改善移植后护理至关重要。
    Managing post-transplant care poses challenges for kidney transplant recipients, often due to food affordability and the ability to participate in physical activity. This study explored recipients\' self-management of care and the influence of social determinants of health on physical activity and diet. A single-center, cross-sectional study recruited 26 participants via My Chart (an Integrated Healthcare Information System patient portal) to complete an 86-question survey. Participants had a mean age of 61 years, and 85% held an associate degree or higher. Body mass index correlated negatively with avoiding high-calorie foods; age and education correlated positively with physical activity. Kidney transplant recipients exhibited limited exercise and frequent high-calorie food consumption. Targeted interventions, particularly promoting regular physical activity, are crucial for improving post-transplant care.
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  • 文章类型: Case Reports
    背景:处理肾移植(KT)后的感染并发症仍然是一个重大挑战。感染是肾移植受者(KTr)的主要非心血管死亡原因。在这一组中,泌尿道特别容易受到感染,导致高发病率和死亡率,以及巨大的经济成本。
    方法:本病例报告介绍了一个84岁的KTr中由囊性瘘引起的广泛大腿化脓性肌炎。病人因急性发作发热被转诊到我院,大腿内侧疼痛和脓尿。CT扫描显示大腿双侧化脓性肌炎,其特征是内收肌中有多个脓肿和需水水平。此外,发现囊性瘘并发耻骨联合骨炎。
    结论:在KTr中,由尿路感染引起的下肢化脓性肌炎极为罕见,并显著恶化这些患者的整体预后。
    BACKGROUND: Managing infectious complications after kidney transplantation (KT) remains a major challenge. Infections are the leading non-cardiovascular cause of death among kidney transplant recipients (KTr). The urinary tract is particularly vulnerable to infections in this group, leading to high levels of morbidity and mortality, as well as significant economic costs.
    METHODS: This case report presents the first documented instance of extensive thigh pyomyositis resulting from cystic fistulae in an 84-year-old KTr. The patient was referred to our hospital with acute onset fever, pain in the inner thighs and pyuria. A CT scan revealed bilateral pyomyositis of the thighs, characterized by multiple abscesses in the adductor muscles and hydroaerobic levels. Additionally, cystic fistulae complicated by pubic symphysis osteitis were identified.
    CONCLUSIONS: In KTr, lower limb pyomyositis resulting from a urinary tract infection is an extremely rare and significantly worsens the overall prognosis for these patients.
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  • 文章类型: Journal Article
    背景:多次接种疫苗对免疫系统衰老过程具有潜在的有害影响。我们检查了用Tozinameran接种SARS-CoV-2疫苗的反应是否与肾移植受者(KTR)的免疫衰老和免疫衰竭有关。
    方法:在这项前瞻性观察研究中,我们观察了39例成人肾移植受者(KTRs),这些受者没有预先存在的抗SARS-CoV-2抗体,并且有稳定的免疫抑制.CD4+和CD8+T细胞亚群[包括CD45RA+CCR7+(初始),CD45RA-CCR7+(T型中央存储器,TCM),CD45RA-CCR7-(T效应子记忆,TEM)和CD45RA+CCR7-(T-效应记忆再表达CD45RA,TEMRA,衰老),在2个时间点评估CD28-(衰老)和PD1(耗尽)]:T1(第3个之前48小时),和T2(第3次Tozinameran剂量给药后3周)。在每个时间点,患者被分为体液和/或细胞反应者和非反应者。
    结果:从T1到T2,CD4+TCM和CD8+TEM升高,而在整个患者队列中,初始CD4+和CD8+比例降低,在响应者中更突出。在T2时,响应者与非响应者相比具有更高的CD8+CD28+[227.15(166)与131.44(121)个细胞/微升,p:0.036],较低的CD4+CD28-T淋巴细胞数量[59.65(66)细胞/μLvs.161.19(92)个细胞/微升,p:0.026]和百分比[6.1(5.5)%vs.20.7(25)%,P:0.04]。
    结论:在KTR中,对疫苗接种的反应与衰老和耗尽的T细胞浓度的增加无关,而是从幼稚到分化激活的T细胞形式的转变。
    BACKGROUND: Multiple vaccinations have potential inimical effects on the immune system aging process. We examined whether response to SARS-CoV-2 vaccination with Tozinameran is associated with immunosenescence and immunoexhaustion in kidney transplant recipients (KTRs).
    METHODS: In this prospective observational study, we observed 39 adult kidney transplant recipients (KTRs) who had no pre-existing anti-SARS-CoV-2 antibodies and were on stable immunosuppression. CD4+ and CD8+ T-cell subpopulations [comprising CD45RA+CCR7+ (naïve), CD45RA-CCR7+ (T-central memory, TCM), CD45RA-CCR7- (T-effector memory, TEM) and CD45RA+CCR7- (T-effector memory re-expressing CD45RA, TEMRA, senescent), CD28- (senescent) and PD1+ (exhausted)] were evaluated at 2 time points: T1 (48 h prior to the 3rd), and T2 (3 weeks following the 3rd Tozinameran dose administration). At each time point, patients were separated into Humoral and/or Cellular Responders and Non-Responders.
    RESULTS: From T1 to T2, CD4+TCM and CD8+TEM were increased, while naïve CD4+ and CD8+ proportions were reduced in the whole cohort of patients, more prominently among responders. At T2, responders compared to non-responders had higher CD8+CD28+ [227.15 (166) vs. 131.44 (121) cells/µL, p: 0.036], lower CD4+CD28- T-lymphocyte numbers [59.65 (66) cells/µL vs. 161.19 (92) cells/µL, p: 0.026] and percentages [6.1 (5.5)% vs. 20.7 (25)%, p: 0.04].
    CONCLUSIONS: In KTRs, response to vaccination is not associated with an expansion of senescent and exhausted T-cell concentrations, but rather with a switch from naïve to differentiated-activated T-cell forms.
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  • 文章类型: Journal Article
    1型人类病毒(HPgV-1),一种无处不在的共生病毒,最近被认为是免疫功能的标志物。存在的数据很少,基因型,和肾移植受者中HPgV-1的分子特征。因此,这项研究的目的是检查患病率和分子特征(周期阈值,来自巴西利亚的肾移植受者中这种病毒感染的基因型),巴西联邦区。通过RT-qPCR评估血浆中的HPgV-1RNA检测。对阳性样品进行病毒基因组5'-UTR部分的测序和系统发育分析。据估计,肾移植受者的HPgV-1患病率为20%。进行的系统发育推断显示,这些患者中最常见的基因型是HPgV-1基因型2(78.9%),由其两个亚型(2A和2B)呈现,其次是基因型1和3(各10.5%)。这项研究提供了有关巴西联邦区肾移植受者中HPgV-1循环和分子特征的新数据。进一步的工作是检查HPgV-1在免疫抑制患者中的作用的基础,包括肾移植受者.
    Human Pegivirus Type 1 (HPgV-1), a ubiquitous commensal virus, has been recently suggested as a marker of immunologic function. There is scarce data for the presence, genotypes, and molecular characteristics of HPgV-1 among kidney transplant recipients. Therefore, the objective of this study was to examine the prevalence and the molecular characteristics (cycle threshold, genotypes) of this viral infection among kidney transplant recipients from the Brasília, Federal District of Brazil. HPgV-1 RNA detection in the plasma was assessed by RT-qPCR. Positive samples were submitted to sequencing and phylogenetic analysis of the 5´-UTR portion of the viral genome. The estimated HPgV-1 prevalence among renal-transplant recipients was 20%. The performed phylogenetic inference revealed that the most frequent genotype among these patients was HPgV-1 genotype 2 (78.9%) presented by its two subgenotypes (2 A and 2B), followed by genotypes 1 and 3 (10.5% each). This study presents new data about the HPgV-1 circulation and molecular characteristics among kidney transplant recipients from the Federal District of Brazil. Further work is fundamental to examine the effect of HPgV-1 among patients with immunological suppression, including kidney transplant recipients.
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  • 文章类型: Journal Article
    移植后早期经常观察到高血糖,并与移植后糖尿病(PTDM)的发展有关。这里,我们评估了针对午后高血糖的持续皮下胰岛素输注(CSII).
    开放标签随机并行3臂设计。
    总共,85例先前没有糖尿病诊断的肾移植受者被随机分配到术后CSII治疗,基础胰岛素,或控制。
    应在下午毛细血管血糖水平≥140mg/dL(7.8mmol/L;CSII和基础胰岛素)或空腹血糖水平≥200mg/dL(11.1mmol/L;对照)时开始胰岛素。
    移植后3个月的血红蛋白A1c(HbA1c)水平(主要终点)。在12个月和24个月时使用口服葡萄糖耐量试验评估PTDM。
    CSII治疗持续到中位第18天和最长第88天。第3个月时,CSII组的HbA1c中位数为5.6%(38mmol/mol),对照组为5.7%(39mmol/mol)(P=0.70),基础胰岛素组为5.4%(36mmol/mol)(P=0.02)。在12个月和24个月,PTDM的几率与对照组相似(优势比[95%置信区间],0.80[0.18-3.49]和0.71[0.15-3.16],分别)和基础胰岛素组(0.96[0.18-5.68]和1.51[0.24-12.84],分别)。CSII和基础胰岛素组发生轻度低血糖事件。
    这项研究受到过时的胰岛素泵技术的限制,CSII的频繁中断,一个复杂的协议,以及对HbA1c测量可靠性的担忧。
    与对照组或基础胰岛素组相比,CSII治疗在降低3个月时的HbA1c水平或在12个月和24个月时的PTDM患病率方面并不优于对照组或基础胰岛素组。
    UNASSIGNED: Hyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia.
    UNASSIGNED: Open-label randomized parallel 3-arm design.
    UNASSIGNED: In total, 85 kidney transplant recipients without previous diabetes diagnosis were randomized to postoperative CSII therapy, basal insulin, or control.
    UNASSIGNED: Insulin was to be initiated at afternoon capillary blood glucose level of ≥140 mg/dL (7.8 mmol/L; CSII and basal insulin) or fasting plasma glucose level of ≥200 mg/dL (11.1 mmol/L; control).
    UNASSIGNED: Hemoglobin A1c (HbA1c) levels at 3 months post-transplant (primary endpoint). PTDM assessed using oral glucose tolerance test at 12 and 24 months.
    UNASSIGNED: CSII therapy lasted until median day 18 and maximum day 88. The median HbA1c value at month 3 was 5.6% (38 mmol/mol) in the CSII group versus 5.7% (39 mmol/mol) in the control group (P = 0.70) and 5.4% (36 mmol/mol) in the basal insulin group (P = 0.02). At months 12 and 24, the odds for PTDM were similar compared with the control group (odds ratios [95% confidence intervals], 0.80 [0.18-3.49] and 0.71 [0.15-3.16], respectively) and the basal insulin group (0.96 [0.18-5.68] and 1.51 [0.24-12.84], respectively). Mild hypoglycemia events occurred in the CSII and the basal insulin groups.
    UNASSIGNED: This study is limited by outdated insulin pump technology, frequent discontinuations of CSII, a complex protocol, and concerns regarding reliability of HbA1c measurements.
    UNASSIGNED: CSII therapy was not superior at reducing HbA1c levels at month 3 or PTDM prevalence at months 12 and 24 compared with the control or basal insulin group.
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  • 文章类型: Letter
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    2019年冠状病毒病(COVID-19)构成了发病率和死亡率的重要风险,实体器官移植后的患者。各种移植协会已在国家和欧洲层面发布了建议,以在入住重症监护病房(ICU)后管理免疫抑制(IS)方案。
    这项研究的目的是根据已发布的建议,评估在重症COVID-19ICU住院的肾移植受者中IS方案最小化策略的充分性。
    所有患者的免疫抑制治疗都被最小化,分别有63%和59%的患者在入院时符合当地和欧洲的建议。ICU入住期间,IS进一步缩减,导致85%(本地)和78%(欧洲)的充足性,相对于准则。最常见的偏差是缺乏霉酚酸的完全戒断(22%)。然而,充足/不充足状态与ICU或1年死亡率无关.
    在这个单中心队列中,与死亡率降低相关的唯一变量是疫苗接种,强调关键问题是感染前的免疫接种,在ICU入住期间不能恢复免疫力。
    UNASSIGNED: Coronavirus disease 2019 (COVID-19) poses an important risk of morbidity and of mortality, in patients after solid organ transplantation. Recommendations have been issued by various transplantation societies at the national and European level to manage the immunosuppressive (IS) regimen upon admission to intensive care unit (ICU).
    UNASSIGNED: The aim of this study was to evaluate the adequacy of IS regimen minimization strategy in kidney transplant recipients hospitalized in an ICU for severe COVID-19, in relation to the issued recommendations.
    UNASSIGNED: The immunosuppressive therapy was minimized in all patients, with respectively 63% and 59% of the patients meeting the local and european recommendations upon admission. During ICU stay, IS was further tapered leading to 85% (local) and 78% (european) adequacy, relative to the guidelines. The most frequent deviation was the lack of complete withdrawal of mycophenolic acid (22%). Nevertheless, the adequacy/inadequacy status was not associated to the ICU- or one-year-mortality.
    UNASSIGNED: In this single-center cohort, the only variable associated with a reduction in mortality was vaccination, emphasizing that the key issue is immunization prior to infection, not restoration of immunity during ICU stay.
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  • 文章类型: Journal Article
    研究背景:在终末期肾病患者中,营养不良与较低的生活质量(QoL)和较低的生存率密切相关。然而,肾移植对营养因素和生活质量的影响尚不清楚。因此,本研究旨在评估肾移植受者(KTRs)的QoL变化,并探讨其与营养因素的关系.材料和方法一项纵向研究包括86名年龄在18-65岁之间的透析患者,他们接受了原发性肾移植(KTx)并随访了一年。体重,生化参数,收集移植前(T0)和移植后6个月(T6)和12个月(T12)的QoL数据。使用效应大小(ES)来测量从T0到T12的KTx对QoL和营养状况的影响。用β系数计算QoL的预测因子,线性回归p<0.05。结果移植对KTRsQoL的影响较大,在1.1为健康变化,0.9为身体健康,一年以上的心理健康(MH)和中度(0.7)。血红蛋白和营养不良受KTx影响,ES分别为2.4和0.6。线性回归分析显示,血红蛋白(β=0.12,p<0.01)可预测身体健康,磷(β=7.82,p<0.05),和霉酚酸酯(MMF)的剂量(β=-0.01,p<0.05)。肥胖可预测心理健康(β=-7.63,p<0.05),血红蛋白(β=0.11,p<0.05),磷(β=8.49,p<0.01)。营养风险指数(NRI)评分(β=0.47,p<0.05)显示健康变化,总胆固醇(β=3.39,p<0.01),和肾功能(β=0.15,p<0.05)。结论从终末期肾脏疾病到移植的转变对QoL和营养指标有积极影响。营养状况,肾功能,霉酚酸酯的剂量是KTR中QoL的重要决定因素。
    Background Malnutrition is strongly associated with lower quality of life (QoL) and lower survival rates in patients with end-stage kidney disease. However, the impact of renal transplantation on nutrition factors and QoL is unclear. Therefore, this study aims to assess changes in QoL and investigate the relationships with nutrition factors among kidney transplant recipients (KTRs). Materials and methods A longitudinal study included 86 dialysis patients aged 18-65 years who underwent primary kidney transplantation (KTx) and were followed up for one year. Body weight, biochemical parameters, and QoL data were collected before transplantation (T0) and at six months (T6) and 12 months (T12) post-transplantation. Effect size (ES) was used to measure the impact of KTx on QoL and nutritional status from T0 to T12. The predictors of QoL were calculated with β-coefficients and p<0.05 in linear regression. Results The ES of transplantation on the QoL of KTRs was large, at 1.1 for health change, 0.9 for physical health, and moderate (0.7) for mental health (MH) over one year. Hemoglobin and malnourished were affected by KTx, with ES being 2.4 and 0.6, respectively. Linear regression showed that physical health was predicted by hemoglobin (β=0.12, p<0.01), phosphorus (β=7.82, p<0.05), and dose of mycophenolate mofetil (MMF) (β=-0.01, p<0.05). Mental health was predicted by obesity (β=-7.63, p<0.05), hemoglobin (β=0.11, p<0.05), and phosphorus (β=8.49, p<0.01). Health change was indicated by nutritional risk index (NRI) score (β=0.47, p<0.05), total cholesterol (β=3.39, p<0.01), and kidney function (β=0.15, p<0.05). Conclusions The transition from end-stage kidney disease to transplantation has positive impacts on QoL and nutrition markers. Nutritional status, kidney function, and the dose of mycophenolate mofetil are significant determinants of QoL in KTRs.
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