Delayed graft function

延迟移植功能
  • 文章类型: Journal Article
    这项研究评估了巴西目前选择冷藏保存解决方案的做法及其对肾移植受者延迟移植功能(DGF)发生率和1年预后的影响。进行了一项回顾性队列研究,包括2014年至2015年期间在18个巴西中心进行的3,134例脑死亡的死者供体肾脏移植。最常用的保存溶液是Euro-collins(EC,55.4%),其次是组氨酸-色氨酸-酮戊二酸(HTK,30%)和乔治·洛佩兹研究所(IGL-1,14.6%)。DGF的发生率为54.4%,11.7%的患者需要透析超过14天,表明DGF延长。在调整混杂变量后,HTK显示DGF的风险明显低于EC(OR0.7350.82500.926),IGL-1也是如此(或0.605.7120.837)。当比较HTK(OR0.4780.5990.749)和IGL-1(OR0.4780.6810.749)与EC时,对于延长的DGF观察到类似的保护作用。在保存解决方案和1年死亡审查的移植物存活率之间没有发现显着关联。总之,EC是最常用的冷藏灌注溶液,与HTK和IGL-1相比,DGF的发生率和持续时间更高,但对1年移植物存活率没有影响。
    This study evaluated the current practices of selecting cold storage preservation solutions in Brazil and their impact on delayed graft function (DGF) incidence and 1-year outcomes in kidney transplant recipients. A retrospective cohort study was conducted, including 3,134 brain-dead deceased donor kidney transplants performed between 2014 and 2015 in 18 Brazilian centers. The most commonly used preservation solution was Euro-collins (EC, 55.4%), followed by Histidine-tryptophan-ketoglutarate (HTK, 30%) and Institut Georges Lopez (IGL-1, 14.6%). The incidence of DGF was 54.4%, with 11.7% of patients requiring dialysis for more than 14 days, indicating prolonged DGF. Upon adjusting for confounding variables, HTK demonstrated a significantly lower risk of DGF than EC (OR 0.7350.82500.926), as did IGL-1 (OR 0.6050.7120.837). Similar protective effects were observed for prolonged DGF when comparing HTK (OR 0.4780.5990.749) and IGL-1 (OR 0.4780.6810.749) against EC. No significant association was found between preservation solutions and 1-year death-censored graft survival. In conclusion, EC was the most frequently used cold storage perfusion solution, demonstrating a higher incidence and duration of DGF compared with HTK and IGL-1, but with no impact on 1-year graft survival.
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  • 文章类型: Clinical Trial Protocol
    背景:大多数实体器官移植源自符合神经系统标准(DNC)死亡标准的供体。在器官捐献者中,脑死亡的生理反应增加了缺血再灌注损伤和移植功能延迟的风险。用钙调磷酸酶抑制的供体预处理可以降低这种风险。
    方法:我们设计了一项多中心安慰剂对照的试点随机试验,涉及加拿大安大略省和魁北克省的9家器官捐赠医院和所有28个移植项目。我们计划招募90名DNC捐赠者和他们的大约324名器官接受者,共有414名参与者。在器官取出前4小时内,捐赠者接受他克莫司0.02mg/kg的静脉输注,或者匹配的安慰剂,同时在重症监护病房监测输注过程中的任何血液动力学变化。在所有研究器官接受者中,我们记录住院前7天的移植物功能测量值,并记录1年后的移植物存活率.我们检查了该试验的可行性,涉及所有符合条件的供体的比例,以及所有符合条件的移植接受者同意接受aCINERGY器官移植的比例,并允许将其健康数据用于研究目的。我们将以95%CI的比例报告这些可行性结果。我们还使用详细的源文件记录在启动和实施本试验中遇到的任何障碍。
    背景:我们将通过出版物和在参与地点和会议上的介绍来传播试验结果。本研究已获得加拿大卫生部(HC6-24-c241083)和所有参与地点的研究伦理委员会以及魁北克(MP-31-2020-3348)和安大略省临床试验(项目#3309)的批准。
    背景:NCT05148715。
    BACKGROUND: Most solid organ transplants originate from donors meeting criteria for death by neurological criteria (DNC). Within the organ donor, physiological responses to brain death increase the risk of ischaemia reperfusion injury and delayed graft function. Donor preconditioning with calcineurin inhibition may reduce this risk.
    METHODS: We designed a multicentre placebo-controlled pilot randomised trial involving nine organ donation hospitals and all 28 transplant programmes in the Canadian provinces of Ontario and Québec. We planned to enrol 90 DNC donors and their approximately 324 organ recipients, totalling 414 participants. Donors receive an intravenous infusion of either tacrolimus 0.02 mg/kg over 4 hours prior to organ retrieval, or a matching placebo, while monitored in an intensive care unit for any haemodynamic changes during the infusion. Among all study organ recipients, we record measures of graft function for the first 7 days in hospital and we will record graft survival after 1 year. We examine the feasibility of this trial with respect to the proportion of all eligible donors enrolled and the proportion of all eligible transplant recipients consenting to receive a CINERGY organ transplant and to allow the use of their health data for study purposes. We will report these feasibility outcomes as proportions with 95% CIs. We also record any barriers encountered in the launch and in the implementation of this trial with detailed source documentation.
    BACKGROUND: We will disseminate trial results through publications and presentations at participating sites and conferences. This study has been approved by Health Canada (HC6-24-c241083) and by the Research Ethics Boards of all participating sites and in Québec (MP-31-2020-3348) and Clinical Trials Ontario (Project #3309).
    BACKGROUND: NCT05148715.
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  • 文章类型: Journal Article
    背景:远程缺血调节(RIC)有可能通过减少缺血再灌注损伤来改善肾移植后的移植物功能;然而,目前的临床证据尚无定论。这项带有试验序贯分析(TSA)的荟萃分析旨在确定RIC是否可以改善肾移植后的移植物功能。
    方法:在PubMed上进行了全面搜索,科克伦图书馆,和EMBASE数据库,直到2023年6月20日,以确定所有研究RIC对肾移植后移植物功能影响的随机对照试验。主要结果是肾移植后移植肾功能延迟(DGF)的发生率。次要结果包括急性排斥反应的发生率,移植物丢失,3个月和12个月估计的肾小球滤过率(eGFR),以及住院时间的长短。亚组分析基于RIC程序(预处理,perconditioning,或后处理),实施地点(上肢或下肢),和移植源(活着或已故的捐赠者)。
    结果:我们的荟萃分析包括8项试验,涉及1038例患者。与对照相比,RIC并未显着降低DGF的发生率(8.8%与15.3%;风险比=0.76,95%置信区间[CI],0.48-1.21,P=0.25,I2=16%),和TSA结果显示,没有达到所需的信息大小。然而,RIC组移植后3个月eGFR显著升高(平均差=2.74ml/min/1.73m2,95%CI:1.44-4.05ml/min/1.73m2,P<0.0001,I2=0%),TSA提出的充分证据。次要结局与其他次要结局具有可比性。RIC的治疗效果在亚组分析之间没有差异。
    结论:在这项采用试验序贯分析的荟萃分析中,RIC并未导致肾移植后DGF发生率的显着降低。尽管如此,RIC与3个月eGFR呈正相关。鉴于本研究纳入的患者数量有限,需要设计良好的大样本量临床试验来验证RIC的肾脏保护益处.
    背景:本系统评价和荟萃分析已在国际前瞻性系统评价注册(编号CRD4202346447)上注册。
    BACKGROUND: Remote ischemic conditioning (RIC) has the potential to benefit graft function following kidney transplantation by reducing ischemia-reperfusion injury; however, the current clinical evidence is inconclusive. This meta-analysis with trial sequential analysis (TSA) aimed to determine whether RIC improves graft function after kidney transplantation.
    METHODS: A comprehensive search was conducted on PubMed, Cochrane Library, and EMBASE databases until June 20, 2023, to identify all randomized controlled trials that examined the impact of RIC on graft function after kidney transplantation. The primary outcome was the incidence of delayed graft function (DGF) post-kidney transplantation. The secondary outcomes included the incidence of acute rejection, graft loss, 3- and 12-month estimated glomerular filtration rates (eGFR), and the length of hospital stay. Subgroup analyses were conducted based on RIC procedures (preconditioning, perconditioning, or postconditioning), implementation sites (upper or lower extremity), and graft source (living or deceased donor).
    RESULTS: Our meta-analysis included eight trials involving 1038 patients. Compared with the control, RIC did not significantly reduce the incidence of DGF (8.8% vs. 15.3%; risk ratio = 0.76, 95% confidence interval [CI], 0.48-1.21, P = 0.25, I2 = 16%), and TSA results showed that the required information size was not reached. However, the RIC group had a significantly increased eGFR at 3 months after transplantation (mean difference = 2.74 ml/min/1.73 m2, 95% CI: 1.44-4.05 ml/min/1.73 m2, P < 0.0001, I2 = 0%), with a sufficient evidence suggested by TSA. The secondary outcomes were comparable between the other secondary outcomes. The treatment effect of RIC did not differ between the subgroup analyses.
    CONCLUSIONS: In this meta-analysis with trial sequential analysis, RIC did not lead to a significant reduction in the incidence of DGF after kidney transplantation. Nonetheless, RIC demonstrated a positive correlation with 3-month eGFR. Given the limited number of patients included in this study, well-designed clinical trials with large sample sizes are required to validate the renoprotective benefits of RIC.
    BACKGROUND: This systematic review and meta-analysis was registered at the International Prospective Register of Systematic Reviews (Number CRD42023464447).
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  • 文章类型: Journal Article
    背景:在肾移植围手术期液体管理中使用平衡晶体而不是生理盐水,对酸碱和电解质平衡的益处以及对术后临床结果的影响仍然是一个有争议的话题。因此,我们进行了这篇综述,以评估与生理盐水相比的平衡溶液对肾移植患者结局的影响.
    方法:我们搜索了MEDLINE,EMBASE,和Cochrane数据库,用于比较肾移植患者中平衡的低氯化物溶液与生理盐水的随机对照试验(RCT)。我们感兴趣的主要结果是移植物功能延迟(DGF)。此外,我们检查了酸碱和电解质的测量,以及术后肾功能。我们使用Mantel-Haenszel检验计算了二元结果的相对风险(RR),和连续数据的平均差(MD),并应用DerSimonian和Laird随机效应模型来解决异质性问题。此外,我们对所有结局进行了试验序贯分析(TSA).
    结果:纳入12个RCTs,共1668名患者;832名(49.9%)被分配接受平衡解决方案。与生理盐水相比,平衡晶体减少了DGF的发生,RR为0.82(95%置信区间[CI],0.71-0.94),P=.005;I²=0%。平衡晶体组的发生率为25%(787个中的194个),生理盐水组为34%(701个中的240个)。此外,我们的TSA支持主要结局结果,并提示样本量足以得出我们的结论.手术结束时的氯化物(MD,-8.80mEq·L-1;95%CI,-13.98至-3.63mEq。L-1;P<.001),碳酸氢盐(MD,2.12mEq·L-1;95%CI,1.02-3.21mEq·L-1;P<.001),pH值(MD,0.06;95%CI,0.04-0.07;P<.001),和碱过量(BE)(MD,2.41mEq·L-1;95%CI,0.88-3.95mEq·L-1;P=.002)显着有利于平衡晶体组和手术结束钾(MD,-0.17mEq·L-1;95%CI,-0.36至0.02mEq·L-1;P=.07)组间没有差异。然而,肌酐在第一次没有差异(MD,-0.06mg·dL-1;95%CI,-0.38至0.26mg·dL-1;P=.71)和第七(MD,-0.06mg·dL-1;95%CI,-0.18至0.06mg·dL-1;P=.30)术后第1天,尿量(MD,-1.12升;95%CI,-3.67至1.43升;P=.39)和第七(MD,-0.01L;95%CI,-0.45至0.42L;P=.95)术后天数。
    结论:在接受肾移植的患者中,平衡的低氯溶液显著减少了DGF的发生,并提供了改善的酸碱和电解质控制。
    BACKGROUND: The use of balanced crystalloids over normal saline for perioperative fluid management during kidney transplantation and its benefits on acid-base and electrolyte balance along with its influence on postoperative clinical outcomes remains a topic of controversy. Therefore, we conducted this review to assess the impact of balanced solutions compared to normal saline on outcomes for kidney transplant patients.
    METHODS: We searched MEDLINE, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) comparing balanced lower-chloride solutions to normal saline in renal transplant patients. Our main outcome of interest was delayed graft function (DGF). Additionally, we examined acid-base and electrolyte measurements, along with postoperative renal function. We computed relative risk (RR) using the Mantel-Haenszel test for binary outcomes, and mean difference (MD) for continuous data, and applied DerSimonian and Laird random-effects models to address heterogeneity. Furthermore, we performed a trial sequential analysis (TSA) for all outcomes.
    RESULTS: Twelve RCTs comprising a total of 1668 patients were included; 832 (49.9%) were assigned to receive balanced solutions. Balanced crystalloids reduced the occurrence of DGF compared to normal saline, with RR of 0.82 (95% confidence interval [CI], 0.71-0.94), P = .005; I² = 0%. The occurrence was 25% (194 of 787) in the balanced crystalloids group and 34% (240 of 701) in the normal saline group. Moreover, our TSA supported the primary outcome result and suggests that the sample size was sufficient for our conclusion. End-of-surgery chloride (MD, -8.80 mEq·L -1 ; 95% CI, -13.98 to -3.63 mEq.L -1 ; P < .001), bicarbonate (MD, 2.12 mEq·L -1 ; 95% CI, 1.02-3.21 mEq·L -1 ; P < .001), pH (MD, 0.06; 95% CI, 0.04-0.07; P < .001), and base excess (BE) (MD, 2.41 mEq·L -1 ; 95% CI, 0.88-3.95 mEq·L -1 ; P = .002) significantly favored the balanced crystalloids groups and the end of surgery potassium (MD, -0.17 mEq·L -1 ; 95% CI, -0.36 to 0.02 mEq·L -1 ; P = .07) did not differ between groups. However, creatinine did not differ in the first (MD, -0.06 mg·dL -1 ; 95% CI, -0.38 to 0.26 mg·dL -1 ; P = .71) and seventh (MD, -0.06 mg·dL -1 ; 95% CI, -0.18 to 0.06 mg·dL -1 ; P = .30) postoperative days nor urine output in the first (MD, -1.12 L; 95% CI, -3.67 to 1.43 L; P = .39) and seventh (MD, -0.01 L; 95% CI, -0.45 to 0.42 L; P = .95) postoperative days.
    CONCLUSIONS: Balanced lower-chloride solutions significantly reduce the occurrence of DGF and provide an improved acid-base and electrolyte control in patients undergoing kidney transplantation.
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  • 文章类型: Journal Article
    背景:移植肾功能延迟(DGF)是肾移植后常见的并发症。本研究旨在评估术后早期乳酸变异与DGF之间的关系。
    方法:这是一个单一的中心,2021年2月至2022年12月在圣路易斯医院进行的回顾性队列研究(APHP,法国)。肾移植后立即(H0)和4小时(H4)测量静脉乳酸水平。主要结果是DGF的发生(在移植到第7天之间需要肾脏替代疗法)。次要结果是并发症的发生(即,死亡,血管血栓形成,出血性休克,泌尿外科并发症(血肿,尿瘤),局部或全身感染)在移植和第7天之间。
    结果:包括200名患者,38例(17.9%)出现DGF。发生DGF的患者在H0和H4之间的静脉乳酸变化较高(-30(IQR-83,-6)%与-15(IQR-62,-11)%,p=.037),但是在发生DGF的患者中,水平的变化更常见为阳性(对应于H0和H4之间随时间的乳酸产生增加)((28(85%)与94(62%),p=.011)。在多变量逻辑回归中,H0和H4之间的静脉乳酸水平变化与DGF发展风险降低密切相关(OR.30[.09-.79],p=.024)。我们没有发现术后高乳酸血症与移植至第7天之间并发症的发生之间存在任何关联。
    结论:DGF是肾移植后常见的并发症。它的早期预测可以帮助医生优化治疗并保护肾脏。肾移植后早期静脉乳酸变化有助于预测DGF的发生。
    Delayed graft function (DGF) is a frequent complication following kidney transplant. This study aimed to assess the association between early post-operative lactate variation and DGF.
    This was a single center, retrospective cohort study between February 2021 and December 2022 in Saint-Louis Hospital (APHP, France). Venous lactate levels were measured immediately (H0) and 4 h (H4) after kidney transplant. The primary outcome was the occurrence of DGF (need for renal replacement therapy between transplantation and day 7). Secondary outcome was the occurrence of complications (i.e., death, vascular thrombosis, hemorrhagic shock, urological complications (hematoma, urinoma), local or systemic infection) between transplant and day 7.
    Two hundred 12 patients were included, and 38 (17.9%) developed DGF. Venous lactate variation between H0 and H4 was higher in patients who developed DGF (-30 (IQR -83, -6)% vs. -15 (IQR -62, -11)%, p = .037), but the variation of level was more often positive (corresponding to an increased lactate production over time between H0 and H4) in patients who developed DGF ((28(85%) vs. 94(62%), p = .011). In multivariate logistic regression, positive venous lactate level variation between H0 and H4 was strongly associated with a reduced risk of developing DGF (OR .30 [.09-.79], p = .024). We did not find any association between post-operative hyperlactatemia and occurrence of complications between transplant and day 7.
    DGF is a frequent complication following kidney transplantation. Its early prediction could help physicians optimize treatment and protect the kidney. Early venous lactate variation after kidney transplant could help to predict the occurrence of DGF.
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  • 文章类型: Journal Article
    肾移植后移植物功能延迟(DGF)很常见,并且与移植物预后较差有关。然而,对DGF后影响移植物存活的因素知之甚少。我们研究了冷缺血时间(CIT)和肾脏供体概况指数(KDPI)与有或没有DGF的死亡脑死亡供体肾脏的长期结局的关系。使用来自芬兰(n=2,637)和来自美国移植接受者科学注册(SRTR)注册(n=61,405)的数据。使用多变量模型研究了KDPI和CIT与有或没有DGF的肾脏移植物存活的关联。在芬兰队列中,849例(32%)肾脏有DGF。DGF和KDPI是移植物丢失的独立危险因素,[HR1.32(95%CI1.14-1.53),p<0.001,每一点HR1.01(95%CI1.01-1.01),p<0.001,分别],但T不是,[HR1.00perCIT小时(95%CI0.99-1.02),p=0.84]。与CIT和KDPI无关,DGF的关联仍然相似。美国队列也有类似的结果,但随着KDPI的升高,DGF的相关性更强。总之,DGF和KDPI,但不是CIT,与移植物存活独立相关。DGF与移植物存活率较差的关联在不同CITs之间是一致的,但在边缘供体中更强。
    Delayed graft function (DGF) after kidney transplantation is common and associated with worse graft outcomes. However, little is known about factors affecting graft survival post-DGF. We studied the association of cold ischemia time (CIT) and Kidney Donor Profile Index (KDPI) with the long-term outcomes of deceased brain-dead donor kidneys with and without DGF. Data from Finland (n = 2,637) and from the US Scientific Registry of Transplant Recipients (SRTR) registry (n = 61,405) was used. The association of KDPI and CIT with the graft survival of kidneys with or without DGF was studied using multivariable models. 849 (32%) kidneys had DGF in the Finnish cohort. DGF and KDPI were independent risk factors for graft loss, [HR 1.32 (95% CI 1.14-1.53), p < 0.001, and HR 1.01 per one point (95% CI 1.01-1.01), p < 0.001, respectively], but CIT was not, [HR 1.00 per CIT hour (95% CI 0.99-1.02), p = 0.84]. The association of DGF remained similar regardless of CIT and KDPI. The US cohort had similar results, but the association of DGF was stronger with higher KDPI. In conclusion, DGF and KDPI, but not CIT, are independently associated with graft survival. The association of DGF with worse graft survival is consistent across different CITs but stronger among marginal donors.
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  • 文章类型: Comparative Study
    肾移植受者移植功能延迟与增加的财务成本和患者负担有关。在肾脏未抽水的肾脏供体资料指数高的供体中,治疗性低温已被证明对延迟的移植物功能具有保护性益处。
    为了确定在低风险非泵肾供体脑死亡后,低温在预防移植功能延迟方面是否优于正常体温。
    在一项多中心随机临床试验中,在2017年8月10日至2020年5月21日之间,被认为是低风险且不需要根据器官采购组织方案进行机器灌注的脑死亡肾脏供体被前瞻性随机分配到低温(34.0-35°C)或正常体温(36.5-37.5°C),在美国的4个器官采购组织中(亚利桑那州,上中西部,太平洋西北部,和德克萨斯州)。最终分析报告的日期为2022年6月15日,基于2021年6月2日从器官共享联合网络收到的数据集。在研究期间,共有509个供体(正常体温:n=245,低温:n=236;1017个肾脏)符合纳入标准。
    供体体温过低(34.0-35.0°C)或正常体温(36.5-37.5°C)。
    主要结果是肾移植受者移植功能延迟,定义为肾移植后第一周内需要透析。主要分析遵循意向治疗原则。
    总共从481个供体移植了934个肾脏,其中474人被随机分配到正常体温组,460人被随机分配到低体温组.两组之间的捐赠者特征相似,总体平均(SD)供体年龄为34.2(11.1)岁,和1.03(0.53)mg/dL的平均供者肌酐水平。标准标准供体(每个治疗组的98%)占主导地位,具有相似的低均值(SD)肾脏供体概况指数(正常体温:28.99[20.46]vs低温:28.32[21.9])。正常体温组和低温组的冷缺血时间相似(15.99[7.9]vs15.45[7.63]小时)。在正常体温组的受者中,有87例(18%)发生了延迟的移植物功能,而在低温组中,有79例(17%)发生了延迟的移植物功能(调整后的比值比,0.92;95%CI,0.64-1.33;P=.66)。
    这项研究的结果表明,在来自脑死亡肾脏供体的低风险非泵送肾脏中,与正常体温相比,治疗性低温似乎不能预防肾移植受者移植功能延迟。
    ClinicalTrials.gov标识符:NCT02525510。
    UNASSIGNED: Delayed graft function in kidney-transplant recipients is associated with increased financial cost and patient burden. In donors with high Kidney Donor Profile Index whose kidneys are not pumped, therapeutic hypothermia has been shown to confer a protective benefit against delayed graft function.
    UNASSIGNED: To determine whether hypothermia is superior to normothermia in preventing delayed graft function in low-risk nonpumped kidney donors after brain death.
    UNASSIGNED: In a multicenter randomized clinical trial, brain-dead kidney donors deemed to be low risk and not requiring machine perfusion per Organ Procurement Organization protocol were prospectively randomized to hypothermia (34.0-35 °C) or normothermia (36.5-37.5 °C) between August 10, 2017, and May 21, 2020, across 4 Organ Procurement Organizations in the US (Arizona, Upper Midwest, Pacific Northwest, and Texas). The final analysis report is dated June 15, 2022, based on the data set received from the United Network for Organ Sharing on June 2, 2021. A total of 509 donors (normothermia: n = 245 and hypothermia: n = 236; 1017 kidneys) met inclusion criteria over the study period.
    UNASSIGNED: Donor hypothermia (34.0-35.0 °C) or normothermia (36.5-37.5 °C).
    UNASSIGNED: The primary outcome was delayed graft function in the kidney recipients, defined as the need for dialysis within the first week following kidney transplant. The primary analysis follows the intent-to-treat principle.
    UNASSIGNED: A total of 934 kidneys were transplanted from 481 donors, of which 474 were randomized to the normothermia group and 460 to the hypothermia group. Donor characteristics were similar between the groups, with overall mean (SD) donor age 34.2 (11.1) years, and the mean donor creatinine level at enrollment of 1.03 (0.53) mg/dL. There was a predominance of Standard Criteria Donors (98% in each treatment arm) with similar low mean (SD) Kidney Donor Profile Index (normothermia: 28.99 [20.46] vs hypothermia: 28.32 [21.9]). Cold ischemia time was similar in the normothermia and hypothermia groups (15.99 [7.9] vs 15.45 [7.63] hours). Delayed graft function developed in 87 of the recipients (18%) in the normothermia group vs 79 (17%) in the hypothermia group (adjusted odds ratio, 0.92; 95% CI, 0.64-1.33; P = .66).
    UNASSIGNED: The findings of this study suggest that, in low-risk non-pumped kidneys from brain-dead kidney donors, therapeutic hypothermia compared with normothermia does not appear to prevent delayed graft function in kidney transplant recipients.
    UNASSIGNED: ClinicalTrials.gov Identifier: NCT02525510.
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  • 文章类型: Journal Article
    在肾移植受者中,移植物功能延迟(DGF)增加移植物衰竭和死亡的风险.在第三阶段,随机化,双盲,安慰剂对照试验,我们研究了肝细胞生长因子模拟物,ANG-3777(每天一次,连续3天,移植后≤30小时开始),248名患者接受了死者的首次肾脏移植。在第360天,ANG-3777组和安慰剂组之间估计的肾小球滤过率(eGFR;主要终点)没有显着差异。到第30天的透析持续时间或在第360天eGFR>30mL/min/1.73m2的患者百分比没有显著的组间差异。ANG-3777和安慰剂组的DGF和急性排斥的发生率相似(68.5%vs69.4%和8.1%vs6.5%,分别)。ANG-3777耐受性良好,与安慰剂相比,移植物失败的发生率在数字上较低(3.2%vs8.1%)。虽然没有足够的证据支持ANG-3777对有肾功能障碍风险的患者进行肾移植,这些发现表明可能需要进一步研究的潜在生物活性。Clinicaltrials.gov编号:NCT02474667。
    In kidney transplant recipients, delayed graft function increases the risk of graft failure and mortality. In a phase 3, randomized, double-blind, placebo-controlled trial, we investigated the hepatocyte growth factor mimetic, ANG-3777 (once daily for 3 consecutive days, starting ≤30 hours posttransplant), in 248 patients receiving a first kidney transplant from a deceased donor. At day 360, estimated glomerular filtration rate (primary endpoint) was not significantly different between the ANG-3777 and placebo groups. There were no significant between-group differences in the duration of dialysis through day 30 or in the percentage of patients with an estimated glomerular filtration rate of >30 mL/min/1.73 m2 at day 360. The incidence of both delayed graft function and acute rejection was similar between ANG-3777 and placebo groups (68.5% vs 69.4% and 8.1% vs 6.5%, respectively). ANG-3777 was well tolerated, and there was a numerically lower incidence of graft failure versus placebo (3.2% vs 8.1%). Although there is insufficient evidence to support an indication of ANG-3777 for patients at risk of renal dysfunction after deceased-donor kidney transplantation, these findings indicate potential biological activity that may warrant further investigation.
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  • 文章类型: Journal Article
    背景:在接受肾衰竭替代治疗的患者中,贫血是常见的。移植前后的贫血可能与肾移植结果有关。因此,目前的研究试图评估贫血之间的关系,延迟的同种异体移植功能(DGF),慢性肾脏移植功能障碍(CAD),从死者的捐献者那里进行肾脏移植后死于任何原因。
    方法:这是一项回顾性研究,对206例肾移植患者的捐献者死亡。我们分析了已故捐献者和肾移植患者的人口统计数据。此外,我们比较了生化参数,贫血状态,DGF和非DGF组之间的药物。之后,我们进行了多变量分析.我们还评估了结果,比如一年内的CAD和十年内的死亡。
    结果:我们观察到移植后一周内DGF组移植前血红蛋白浓度(Hb)的频率较低,但供体血清肌酐和红细胞输注的频率较高。此外,移植前Hb浓度与DGF之间存在独立关联[OR0.252,95CI:0.159-0.401;p<0.001].肾移植六个月后的Hb浓度与CAD[OR0.798,95%CI:0.687-0.926;p=0.003]和任何原因死亡之间也存在关联。
    结论:发现移植前贫血与DGF之间以及移植后6个月贫血与CAD和任何原因导致的死亡之间存在关联。因此,移植前或移植后的贫血会影响从已故供体接受肾脏移植的患者的预后.
    BACKGROUND: Anemia is frequent in patients undergoing replacement therapy for kidney failure. Anemia in the pre- and post-transplantation period might be related to kidney transplant outcomes. The current study therefore sought to assess the relationship between anemia, delayed allograft function (DGF), chronic kidney allograft dysfunction (CAD), and death from any cause following kidney transplantation from a deceased donor.
    METHODS: This was a retrospective study with 206 kidney transplant patients of deceased donors. We analyzed deceased donors\' and kidney transplant patients\' demographic data. Moreover, we compared biochemical parameters, anemia status, and medicines between DGF and non-DGF groups. Afterward, we performed a multivariate analysis. We also evaluated outcomes, such as CAD within one year and death in ten years.
    RESULTS: We observed a lower frequency of pre-transplant hemoglobin concentration (Hb) but higher frequency of donor-serum creatinine and red blood transfusion within one week after transplantation in the group with DGF. In addition, there was an independent association between Hb concentration before transplantation and DGF [OR 0.252, 95%CI: 0.159-0.401; p < 0.001]. There was also an association between Hb concentration after six months of kidney transplantation and both CAD [OR 0.798, 95% CI: 0.687-0.926; p = 0.003] and death from any cause.
    CONCLUSIONS: An association was found between pre-transplantation anemia and DGF and between anemia six months after transplantation and both CAD and death by any cause. Thus, anemia before or after transplantation affects the outcomes for patients who have undergone kidney transplantation from a deceased donor.
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  • 文章类型: Journal Article
    UNASSIGNED: The relationship between post-operative urine output (UO) following kidney transplantation and long-term graft function has not been well described.
    UNASSIGNED: In this study, we examined the association between decreased UO on post-operative day 1 (POD1) and post-transplant outcomes.
    UNASSIGNED: This is a retrospective cohort study.
    UNASSIGNED: Atlantic Canada.
    UNASSIGNED: Patients from the 4 Atlantic Canadian provinces (Nova Scotia, New Brunswick, Newfoundland, and Prince Edward Island) who received a live or deceased donor kidney transplant from 2006 through 2019 through the multiorgan transplant program at the Queen Elizabeth II Health Sciences Centre (QEII) hospital in Halifax, Nova Scotia.
    UNASSIGNED: Using multivariable Cox proportional hazards models, we assessed the association of low POD1 UO (defined as ≤1000 mL) with death-censored graft loss (DCGL). In secondary analyses, we used adjusted logistic regression or Cox models as appropriate to assess the impact of UO on delayed graft function (DGF), prolonged length of stay (greater than the median for the entire cohort), and death.
    UNASSIGNED: Of the 991 patients included, 151 (15.2%) had a UO ≤1000 mL on POD1. Low UO was independently associated with DCGL (hazard ratio [HR] = 4.00, 95% confidence interval [CI] = 95% CI = 1.55-10.32), DGF (odds ratio [OR] = 45.25, 95% CI = 23.00-89.02), and prolonged length of stay (OR = 5.06, 95% CI = 2.95-8.69), but not death (HR = 0.81, 95% CI = 0.31-2.09).
    UNASSIGNED: This was a single-center, retrospective, observational study and therefore has inherent limitations of generalizability, data collection, and residual confounding.
    UNASSIGNED: Overall, reduced post-operative UO following kidney transplantation is associated with an increased risk of DCGL, DGF, and prolonged hospital length of stay.
    UNASSIGNED: Le lien entre la diurèse postopératoire après une transplantation rénale et la fonction du greffon à long terme n’a pas été bien décrit.
    UNASSIGNED: Dans cette étude, nous avons examiné l’association entre la diminution de la diurèse au jour 1 postopératoire et les résultats après la transplantation.
    UNASSIGNED: Étude de cohorte rétrospective.
    UNASSIGNED: Canada atlantique.
    UNASSIGNED: Des patients des quatre provinces du Canada atlantique (Nouvelle-Écosse, Nouveau-Brunswick, Terre-Neuve et Île-du-Prince-Édouard) ayant reçu une greffe de rein provenant d’un donneur vivant ou décédé entre 2006 et 2019 dans le cadre du programme de transplantation multiorganes de l’hôpital QEII d’Halifax (Nouvelle-Écosse).
    UNASSIGNED: À l’aide de modèles à risques proportionnels de Cox multivariés, nous avons évalué l’association entre une faible diurèse (définie comme ≤ 1 000 ml) et la perte du greffon censurée par le décès (PGCD). Dans les analyses secondaires, nous avons utilisé des modèles de Cox ou des modèles de régression logistique ajustés, selon le cas, pour évaluer l’effet de la diurèse sur la fonction retardée du greffon, la durée prolongée du séjour (supérieure à la médiane pour l’ensemble de la cohorte) et le décès.
    UNASSIGNED: Des 991 patients inclus, 151 (15,2%) présentaient une diurèse inférieure à 1 000 ml au jour 1 postopératoire. Une faible diurèse a été indépendamment associée à la PGCD (rapport de risque [RR]: 4,00; IC 95 %: 1,55-10,32), à une fonction retardée du greffon (rapport de cotes [RC]: 45,25; IC 95 %: 23,00-89,02) et à un séjour prolongé à l’hôpital (RC: 5,06; IC 95 %: 2,95-8,69), mais pas au décès (RR: 0,81; IC 95 %: 0,31-2,09).
    UNASSIGNED: Il s’agissait d’une étude observationnelle rétrospective monocentrique. L’étude présente ainsi des limites inhérentes à la généralisabilité, à la collecte des données et aux facteurs confondants résiduels.
    UNASSIGNED: Dans l’ensemble, une diminution de la diurèse postopératoire après une transplantation rénale est associée à un risque accru de PGCD et de fonction retardée du greffon, ainsi qu’à un séjour prolongé à l’hôpital.
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