DataSheet_1_Progression of histological lesions after ABO incompatible kidney transplantation.docx

Recent large meta-analyses suggested a poorer long-term patients’ and grafts’ outcomes after ABO incompatible (ABOi) living-donor kidney transplantation (LDKT) compared to ABO compatible LDKT. However, little is known about the long-term histological pattern after ABOi LDKT. We compared the histological features observed on protocol biopsies from 03/11 to 11/19 in 94 ABOi LDKT (including 14 with preformed Donor Specific Antibodies, pDSAs), 27 LDKT ABO compatible (ABOc) with pDSAs, and 21 ABOc without pDSAs) during the first five years post transplantation. During the first 5 years post-transplantation, a progression of chronic lesions (patients with a ci >0 raised from 11% to 65%, p<0.0001, patients with a ct >0 raised from 29% to 78%, p<0.0001) was observed in ABOi LDKT without pDSAs. Histological patterns of evolution were comparable to those observed in ABOc kidney transplant patients. Microvascular inflammation was lower in ABOi LDKT without pDSAs compared to those with pDSAs (ABOi or ABOc). At last follow-up, 28 months, IQR (15-48) post-transplantation, 29 patients (36%) had a severe graft dysfunction (defined by a CKD-epi eGFR < 30 mL/min/1.73m²). The donor age was a predictive factor for the development of severe kidney allograft dysfunction at last follow-up (HR= 1.05, 95% CI [1.05-1.10], p= 0.03).
Hence, long-term histological analysis of ABOi LDKT shows only an increase of chronic interstitial and tubular atrophy changes, without active lesions. These data confirm that ABOi LDKT programs can be securely developed.

近期多项大型荟萃分析结果显示，相较于ABO血型相容（ABO compatible, ABOc）活体供肾移植（living-donor kidney transplantation, LDKT），ABO血型不相容（ABO incompatible, ABOi）活体供肾移植患者的长期预后及移植物预后均更差。然而，目前学界对ABOi LDKT术后的长期组织学特征仍知之甚少。本研究对比了2011年3月至2019年11月期间，94例ABOi LDKT患者（其中14例存在预存供者特异性抗体（preformed Donor Specific Antibodies, pDSAs））、27例伴pDSAs的ABOc LDKT患者，以及21例无pDSAs的ABOc LDKT患者在移植术后前5年的方案活检组织学特征。

在移植术后前5年，无pDSAs的ABOi LDKT患者的慢性病变呈进展趋势：ci>0的患者占比从11%升至65%（p<0.0001），ct>0的患者占比从29%升至78%（p<0.0001）。其组织学演化模式与ABOc肾移植患者无明显差异。无pDSAs的ABOi LDKT患者的微血管炎症程度低于伴pDSAs的ABOi或ABOc LDKT患者。在末次随访时（移植后中位28个月，四分位距15~48个月），共有29例患者（36%）出现严重移植物功能障碍（定义为CKD-EPI估算肾小球滤过率<30 mL/min/1.73m²）。供者年龄是末次随访时发生严重肾移植物功能障碍的预测因素（风险比=1.05，95%置信区间[1.05~1.10]，p=0.03）。

综上，ABOi LDKT的长期组织学分析仅显示慢性间质及肾小管萎缩病变的进展，未出现活动性损伤。上述数据证实，ABOi LDKT临床项目可安全开展。