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Histological characteristics of Acute Tubular Injury during Delayed Graft Function predict renal function after renal transplantation

机译:延迟移植功能期间急性肾小管损伤的组织学特征可预测肾移植后的肾功能

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Acute Tubular Injury (ATI) is the leading cause of Delayed Graft Function (DGF) after renal transplantation (RTX). Biopsies taken 1?week after RTX often show extensive tubular damage, which in most cases resolves due to the high regenerative capacity of the kidney. Not much is known about the relation between histological parameters of renal damage and regeneration immediately after RTX and renal outcome in patients with DGF. We retrospectively evaluated 94 patients with DGF due to ATI only. Biopsies were scored for morphological characteristics of renal damage (edema, casts, vacuolization, and dilatation) by three independent blinded observers. The regenerative potential was quantified by tubular cells expressing markers of proliferation (Ki67) and dedifferentiation (CD133). Parameters were related to renal function after recovery (CKD‐EPI 3, 6, and 12?months posttransplantation). Quantification of morphological characteristics was reproducible among observers (Kendall's W?≥?0.56). In a linear mixed model, edema and casts significantly associated with eGFR within the first year independently of clinical characteristics. Combined with donor age, edema and casts outperformed the Nyberg score, a well–validated clinical score to predict eGFR within the first year after transplantation ( R 2 ?=?0.29 vs. R 2 ?=?0.14). Although the number of Ki67+ cells correlated to the extent of acute damage, neither CD133 nor Ki67 correlated with renal functional recovery. In conclusion, the morphological characteristics of ATI immediately after RTX correlate with graft function after DGF. Despite the crucial role of regeneration in recovery after ATI, we did not find a correlation between dedifferentiation marker CD133 or proliferation marker Ki67 and renal recovery after DGF.
机译:急性肾小管损伤(ATI)是肾移植(RTX)后延迟移植物功能(DGF)的主要原因。在RTX后1周进行的活检通常显示出广泛的肾小管损伤,在大多数情况下,由于肾脏的高再生能力而得以解决。对于DGF患者,RTX术后肾脏损害的组织学参数和再生与肾预后之间的关系还不清楚。我们回顾性评估了仅由ATI引起的94例DGF患者。由三个独立的盲人观察者对活检组织的肾脏损害形态特征进行了评分(水肿,管型,空泡化和扩张)。再生潜能通过表达增殖(Ki67)和去分化(CD133)标记的肾小管细胞来定量。参数与恢复后的肾功能有关(CKD-EPI在移植后3、6和12个月)。观察者之间的形态特征量化是可重复的(肯德尔W≥≥0.56)。在线性混合模型中,第一年内水肿和铸型与eGFR显着相关,与临床特征无关。结合供体年龄,水肿和管型比Nyberg评分好,Nyberg评分是一项经过充分验证的临床评分,可预测移植后第一年内的eGFR(R 2≥0.29vs. R 2≥0.14)。尽管Ki67 +细胞的数量与急性损伤的程度有关,但CD133和Ki67均与肾功能恢复无关。总之,RTX后立即发生的ATI的形态特征与DGF后的移植物功能相关。尽管再生在ATI后恢复中起着至关重要的作用,但我们未发现去分化标记CD133或增殖标记Ki67与DGF后肾恢复之间的相关性。

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