肾移植受者微血管炎症与临床结局
Microvascular Inflammation of Kidney Allografts and Clinical Outcomes.
作者信息
Sablik Marta, Sannier Aurélie, Raynaud Marc, Goutaudier Valentin, Divard Gillian, Astor Brad C, Weng Patricia, Smith Jodi, Garro Rouba, Warady Bradley A, Zahr Rima S, Twombley Katherine, Dharnidharka Vikas R, Dandamudi Raja S, Fila Marc, Huang Edmund, Sellier-Leclerc Anne-Laure, Tönshoff Burkhard, Rabant Marion, Verine Jérôme, Del Bello Arnaud, Berney Thierry, Boyer Olivia, Catar Rusan Ali, Danger Richard, Giral Magali, Yoo Daniel, Girardin François R, Alsadi Alaa, Gourraud Pierre-Antoine, Morelon Emmanuel, Le Quintrec Moglie, Try Mélanie, Villard Jean, Zhong Weixiong, Bestard Oriol, Budde Klemens, Chauveau Bertrand, Couzi Lionel, Brouard Sophie, Hogan Julien, Legendre Christophe, Anglicheau Dany, Aubert Olivier, Kamar Nassim, Lefaucheur Carmen, Loupy Alexandre
机构信息
Université Paris Cité, INSERM Unité 970, Paris Institute for Transplantation and Organ Regeneration, Paris.
Department of Pathology, Bichat Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris.
出版信息
N Engl J Med. 2025 Feb 20;392(8):763-776. doi: 10.1056/NEJMoa2408835. Epub 2024 Oct 24.
BACKGROUND
The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear.
METHODS
We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023. We integrated clinical and pathological data to classify biopsy specimens according to the 2022 Banff Classification of Renal Allograft Pathology, which includes two new diagnostic categories: probable antibody-mediated rejection and microvascular inflammation without evidence of an antibody-mediated response. We then assessed the association between the newly recognized microvascular inflammation phenotypes and allograft survival and disease progression.
RESULTS
A total of 16,293 kidney-transplant biopsy specimens from 6798 patients were assessed. We identified the newly recognized microvascular inflammation phenotypes in 788 specimens, of which 641 were previously categorized as specimens with no evidence of rejection. As compared with patients without rejection, the hazard ratio for graft loss was 2.1 (95% confidence interval [CI], 1.5 to 3.1) among patients with microvascular inflammation without evidence of an antibody-mediated response and 2.7 (95% CI, 2.2 to 3.3) among patients with antibody-mediated rejection. Patients with a diagnosis of probable antibody-mediated rejection had a higher risk of graft failure beyond year 5 after biopsy than those without rejection (hazard ratio, 1.7; 95% CI, 0.8 to 3.5). Patients with a diagnosis of either newly recognized microvascular inflammation phenotype had a higher risk of progression of transplant glomerulopathy during follow-up than patients without microvascular inflammation.
CONCLUSIONS
Microvascular inflammation in kidney allografts includes distinct phenotypes, with various disease progression and allograft outcomes. Our findings support the clinical use of additional rejection phenotypes to standardize diagnostics for kidney allografts. (Funded by OrganX. ClinicalTrials.gov number, NCT06496269.).
背景
移植肾微血管炎症的临床表现具有异质性，这对肾移植的成功构成了重大挑战。微血管炎症对移植肾结局的影响尚不清楚。
方法
我们进行了一项队列研究，纳入了来自欧洲和北美的30多个移植中心的肾移植受者，这些受者在2004年至2023年间接受了移植肾活检。我们整合了临床和病理数据，根据2022年《肾移植病理Banff分类》对活检标本进行分类，该分类包括两个新的诊断类别：可能的抗体介导排斥反应和无微血管炎症证据的抗体介导反应。然后，我们评估了新识别的微血管炎症表型与移植肾存活和疾病进展之间的关联。
结果
共评估了来自6798例患者的16293份肾移植活检标本。我们在788份标本中识别出了新识别的微血管炎症表型，其中641份标本之前被归类为无排斥反应证据的标本。与无排斥反应的患者相比，无微血管炎症证据的抗体介导反应患者的移植肾丢失风险比为2.1（95%置信区间[CI]，1.5至3.1），抗体介导排斥反应患者的移植肾丢失风险比为2.7（95%CI，2.2至3.3）。诊断为可能的抗体介导排斥反应的患者在活检后第5年以后发生移植肾失败的风险高于无排斥反应的患者（风险比，1.7；95%CI，0.8至3.5）。诊断为任何一种新识别的微血管炎症表型的患者在随访期间发生移植肾小球病进展的风险高于无微血管炎症的患者。
结论
移植肾微血管炎症包括不同的表型，具有不同的疾病进展和移植肾结局。我们的研究结果支持临床使用额外的排斥反应表型来规范移植肾的诊断。（由OrganX资助。ClinicalTrials.gov编号，NCT06496269。）
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