Jayanti Sumedh, Beruni Nadim A, Chui Juanita N, Deng Danny, Liang Amy, Chong Anita S, Craig Jonathan C, Foster Bethany, Howell Martin, Kim Siah, Mannon Roslyn B, Sapir-Pichhadze Ruth, Scholes-Robertson Nicole J, Strauss Alexandra T, Jaure Allison, West Lori, Cooper Tess E, Wong Germaine
Westmead Hospital, Westmead, Australia.
The University of Sydney, Sydney, Australia.
Cochrane Database Syst Rev. 2024 Dec 19;12(12):CD014966. doi: 10.1002/14651858.CD014966.pub2.
BACKGROUND: Sex, as a biological construct, and gender, defined as the cultural attitudes and behaviours attributed by society, may be associated with allograft loss, death, cancer, and rejection. Other factors, such as recipient age and donor sex, may modify the association between sex/gender and post-transplant outcomes. OBJECTIVES: We sought to evaluate the prognostic effects of recipient sex and, separately, gender as independent predictors of graft loss, death, cancer, and allograft rejection following kidney or simultaneous pancreas-kidney (SPK) transplantation. We aimed to evaluate this prognostic effect by defining the relationship between recipient sex or gender and post-transplantation outcomes identifying reasons for variations between sexes and genders, and then quantifying the magnitude of this relationship. SEARCH METHODS: We searched MEDLINE and EMBASE databases from inception up to 12 April 2023, through contact with the Cochrane Kidney and Transplant Information Specialist, using search terms relevant to this review and no language restrictions. SELECTION CRITERIA: Cohort, case-control, or cross-sectional studies were included if sex or gender were the primary exposure and clearly defined. Studies needed to focus on our defined outcomes post-transplantation. Sex was defined as the chromosomal, gonadal, and anatomical characteristics associated with the biological sex, and we used the terms "males" and "females". Gender was defined as the attitudes and behaviours that a given culture associates with a person's biological sex, and we used the terms "men" and "women". DATA COLLECTION AND ANALYSIS: Two authors independently assessed the references for eligibility, extracted the data and assessed the risk of bias using the Quality in Prognosis Studies (QUIPS) tool. Whenever appropriate, we performed random-effects meta-analyses to estimate the mean difference in outcomes. The outcomes of interest included the Standardised Outcomes in Nephrology-Kidney Transplant (SONG-Tx) core outcomes, allograft loss, death, cancer (overall incidence and site-specific) and acute or chronic graft rejection. MAIN RESULTS: Fifty-three studies (2,144,613 patients; range 59 to 407,963) conducted between 1990 and 2023 were included. Sixteen studies were conducted in the Americas, 12 in Europe, 11 in the Western Pacific, four in the Eastern Mediterranean, three in Africa, two in Southeast Asia, and five across multiple regions. All but one study focused on sex rather than gender as the primary exposure of interest. The number identified as male was 54%; 49 studies included kidney transplant recipients, and four studies included SPK transplant recipients. Twenty-four studies included adults and children, 25 studies included only adults, and four studies included only children. Data from 33 studies were included in the meta-analyses. Among these, six studies presented unadjusted hazard ratios (HRs) that assessed the effect of recipient sex on kidney allograft loss. The other studies reported risk ratios (RRs) for the pre-defined outcomes. Notably, the decision to restrict the meta-analyses to unadjusted estimates arose from the variation in covariate adjustment methods across studies, lacking a common set of adjusted variables. Only three studies considered the modifying effect of recipient age on graft loss or death, which is likely crucial to evaluating sex differences in post-transplant outcomes. No studies considered the modifying effect of recipient age on cancer incidence or allograft rejection risk. In low certainty evidence, compared with male recipients, being female may make little or no difference in kidney allograft loss post-transplantation (7 studies, 5843 patients: RR 0.91, 95% CI 0.73 to 1.12; I = 73%). This was also observed in studies that included time-to-event analyses (6 studies, 238,937 patients; HR 1.07, 95% CI, 0.95 to 1.20; I = 44%). Two recent large registry-based cohort studies that considered the modifying effects of donor sex and recipient age showed that female recipients under 45 years of age had significantly higher graft loss rates than age-matched male recipients in the setting of a male donor. In contrast, female recipients 60 years and older had lower graft loss rates than age-matched male recipients, regardless of donor sex. Compared with male recipients, being female may make little or no difference in death up to 30 years post-transplantation; however, the evidence is very uncertain (13 studies, 60,818 patients: RR 0.94, 95% CI 0.81 to 1.09; I = 92%). Studies that considered the modifying effect of recipient age and donor sex showed that female recipients had a higher excess death risk than males under 45 years of age in the setting of a male donor. Compared with male recipients, being female may make little or no difference in cancer incidence up to 20 years post-transplantation; however, the evidence is very uncertain (7 studies, 25,076 patients; RR 0.84, 95% CI 0.70 to 1.01; I = 60%). Compared with male recipients, being female may make little or no difference in the incidence of acute and chronic kidney allograft rejection up to 15 years post-transplantation (9 studies, 6158 patients: RR 0.89, 95% CI 0.75 to 1.05; I =54%; low certainty evidence). One study assessed gender and reported that when compared with men, women experienced better five-year survival in high (HR 0.71, 95% CI 0.59 to 0.87) and middle-income areas (HR 0.82, 95% CI 0.74 to 0.92), with no difference in low-income areas (HR 0.85, 95% CI 0.72 to 1.01). There was considerable uncertainty regarding any association between sex or gender and post-transplant patient-relevant outcomes. This was primarily due to clinical and methodological heterogeneity. The observed clinical heterogeneity between studies could be attributed to diverse patient characteristics within sample populations. As a result of limited sex-stratified demographic data being provided, further investigation of this heterogeneity was constrained. However, factors contributing to this finding may include recipient age, donor age, types, and sex. Methodological heterogeneity was noted with the interchangeable use of sex and gender, outcome misclassification, the use of different measures of effects, inconsistent covariate profiles, and disregard for important effect modification. AUTHORS' CONCLUSIONS: There is very low to low certainty evidence to suggest there are no differences in kidney and pancreas allograft survival, patient survival, cancer, and acute and chronic allograft rejection between male and female kidney and SPK transplant recipients.
背景:性别作为一种生物学概念,而社会赋予文化态度和行为定义的性别角色,可能与同种异体移植失败、死亡、癌症及排斥反应相关。其他因素,如受者年龄和供者性别,可能会改变性别与移植后结局之间的关联。 目的:我们试图评估受者性别以及性别角色作为肾移植或胰肾联合移植(SPK)后移植失败、死亡、癌症和同种异体移植排斥反应独立预测因素的预后影响。我们旨在通过定义受者性别或性别角色与移植后结局之间的关系,找出性别差异的原因,然后量化这种关系的程度,来评估这种预后影响。 检索方法:我们检索了MEDLINE和EMBASE数据库,从数据库建立至2023年4月12日,通过联系Cochrane肾脏与移植信息专家,使用与本综述相关的检索词,且无语言限制。 选择标准:纳入队列研究、病例对照研究或横断面研究,若性别或性别角色为主要暴露因素且定义明确。研究需聚焦于我们定义的移植后结局。性别定义为与生物性别相关的染色体、性腺和解剖学特征,我们使用“男性”和“女性”这两个术语。性别角色定义为特定文化赋予一个人生物性别的态度和行为,我们使用“男性”和“女性”这两个术语。 数据收集与分析:两位作者独立评估参考文献的合格性,提取数据,并使用预预后研究质量(QUIPS)工具评估偏倚风险。在适当情况下,我们进行随机效应荟萃分析以估计结局的平均差异。感兴趣的结局包括肾脏病学 - 肾移植标准化结局(SONG - Tx)核心结局、移植失败、死亡、癌症(总体发病率和特定部位发病率)以及急性或慢性移植排斥反应。 主要结果:纳入了1990年至2023年期间开展的53项研究(2,144,613例患者;范围为59至407,963例)。16项研究在美洲开展,12项在欧洲,11项在西太平洋地区,4项在东地中海地区,3项在非洲,2项在东南亚,5项在多个地区开展。除一项研究外,所有研究均将性别而非性别角色作为主要关注的暴露因素。确定为男性的比例为54%;49项研究纳入了肾移植受者,4项研究纳入了SPK移植受者。24项研究纳入了成人和儿童,25项研究仅纳入了成人,4项研究仅纳入了儿童。33项研究的数据纳入了荟萃分析。其中,6项研究呈现了未调整的风险比(HRs),评估了受者性别对肾移植失败的影响。其他研究报告了预定义结局的风险比(RRs)。值得注意的是,将荟萃分析限制为未调整估计值的决定源于各研究中协变量调整方法的差异,缺乏一组共同的调整变量。只有三项研究考虑了受者年龄对移植失败或死亡的修正作用,而这可能对评估移植后结局的性别差异至关重要。没有研究考虑受者年龄对癌症发病率或移植排斥风险的修正作用。在低确定性证据中,与男性受者相比,女性在肾移植后移植失败方面可能几乎没有差异或无差异(7项研究,5843例患者:RR 0.91,95%CI 0.73至1.12;I² = 73%)。在纳入事件发生时间分析的研究中也观察到了这一点(6项研究,238,937例患者;HR 1.07,95%CI 0.95至1.20;I² = 44%)。两项近期基于大型登记处的队列研究考虑了供者性别和受者年龄的修正作用,结果显示在男性供者的情况下,45岁以下的女性受者移植失败率显著高于年龄匹配的男性受者。相比之下,60岁及以上的女性受者移植失败率低于年龄匹配的男性受者,无论供者性别如何。与男性受者相比,女性在移植后30年内死亡方面可能几乎没有差异或无差异;然而,证据非常不确定(13项研究,60,818例患者:RR 0.94,95%CI 0.81至1.09;I² = 92%)。考虑受者年龄和供者性别的修正作用的研究表明,在男性供者的情况下,45岁以下的女性受者比男性受者有更高的额外死亡风险。与男性受者相比,女性在移植后20年内癌症发病率方面可能几乎没有差异或无差异;然而,证据非常不确定(7项研究,25,076例患者;RR 0.84,95%CI 0.70至1.01;I² = 60%)。与男性受者相比,女性在移植后15年内急性和慢性肾移植排斥反应发生率方面可能几乎没有差异或无差异(9项研究,6158例患者:RR 0.89,95%CI 0.75至1.05;I² = 54%;低确定性证据)。一项研究评估了性别角色,报告称与男性相比,女性在高收入地区(HR 0.71,95%CI 0.59至0.87)和中等收入地区(HR 0.82,95%CI 0.74至0.92)的五年生存率更高,在低收入地区无差异(HR 0.85,95%CI 0.72至1.01)。关于性别或性别角色与移植后患者相关结局之间的任何关联存在相当大的不确定性。这主要是由于临床和方法学异质性。研究中观察到的临床异质性可归因于样本人群中不同的患者特征。由于提供的性别分层人口统计学数据有限,对这种异质性的进一步研究受到限制。然而,导致这一结果的因素可能包括受者年龄、供者年龄、类型和性别。方法学异质性表现为性别和性别角色的互换使用、结局错误分类、效应测量方法不同、协变量概况不一致以及对重要效应修正的忽视。 作者结论:有极低至低确定性证据表明,男性和女性肾移植及SPK移植受者在肾和胰腺移植存活、患者存活、癌症以及急性和慢性移植排斥反应方面没有差异。
Cochrane Database Syst Rev. 2024-12-19
Cochrane Database Syst Rev. 2020-10-19
Cochrane Database Syst Rev. 2017-7-20
Cochrane Database Syst Rev. 2025-3-20
Cochrane Database Syst Rev. 2018-2-6
Cochrane Database Syst Rev. 2022-9-26
Cochrane Database Syst Rev. 2022-9-12
Cochrane Database Syst Rev. 2025-4-8
Cochrane Database Syst Rev. 2017-12-22
Cochrane Database Syst Rev. 2017-7-21
Bioinformation. 2025-4-30
Front Med (Lausanne). 2022-9-26
Clin Transplant. 2022-12
Semin Nephrol. 2022-3
Front Med (Lausanne). 2022-1-24
Transplantation. 2022-7-1