Urine marker analysis identifies evidence for persistent glomerular podocyte injury across allograft lifespan.
Urine marker analysis identifies evidence for persistent glomerular podocyte injury across allograft lifespan.
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DOI：
10.1111/ctr.14457
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发表时间：
2021-11
影响因子：
2.1
通讯作者：
Wiggins RC
中科院分区：
文献类型：
--
作者：
Naik AS;Aqeel J;Wang SQ;Chowdhury M;He K;Wiggins RC
长期肾移植（KT）存活率一直相对停滞。协议活检研究表明，肾小球硬化症是一个显着的贡献者长期移植失败。我们先前证实，移植后第1年足细胞的丢失预示着移植物的长期存活。然而，增加足细胞损失是否在KT的寿命期间持续仍不清楚。我们对来自260名KT受者的1，182份尿液样本进行了横断面分析，这些受者在移植后长达19年。尿颗粒mRNA测定足细胞（NPHS 2/podocin和nephrin/NPHS 1），远端小管（水通道蛋白2）和促纤维化细胞因子（TGF β 1）。多变量广义估计方程用于获得这些标记物随KT后时间推移的“群体平均”效应。与早期应力一致，足细胞和肾小管标记物在KT后立即增加。然而，只有足细胞标记物持续增加长期。随着时间的推移，肥大性应激在驱动足细胞损失中的作用通过其与移植时供体BMI、受体BMI和供体-受体BMI不匹配的关联来暗示。此外，尿颗粒podocin mRNA与尿TGF β 1、蛋白尿和eGFR降低相关，从而将足细胞损伤与同种异体移植物纤维化和存活联系起来。总之，我们观察到，足细胞损失继续长期后KT表明在驱动后期移植物损失的重要作用。
Long-term kidney transplant (KT) survival has remained relatively stagnant. Protocol biopsy studies suggest that glomerulosclerosis is a significant contributor to long-term graft failure. We previously demonstrated that podocyte loss in the 1styear post-transplantation predicted long-term allograft survival. However, whether increased podocyte loss continues over the lifespan of a KT remains unclear. We performed a cross-sectional analysis of 1,182 urine samples from 260 KT recipients up to 19-years after transplantation. Urine pellet mRNAs were assayed for podocyte (NPHS2/podocin and nephrin/NPHS1), distal tubule (aquaporin2), and profibrotic cytokine (TGFbeta1). Multivariable generalized estimating equations were used to obtain “population-averaged” effects for these markers over time post-KT. Consistent with early stresses both podocyte and tubular markers increased immediately post-KT. However, only podocyte markers continued to increase long-term. A role for hypertrophic stresses in driving podocyte loss over time is implied by their association with donor BMI, recipient BMI and donor-recipient BMI mismatch at transplantation. Furthermore, urine pellet podocin mRNA was associated with urine TGFbeta1, proteinuria and reduced eGFR, thereby linking podocyte injury to allograft fibrosis and survival. In conclusion we observed that podocyte loss continues long-term post-KT suggesting an important role in driving late graft loss.
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影响因子：
6.2
作者：
Naik, Abhijit S.;Sakhuja, Ankit;Lentine, Krista L.
通讯作者：
Lentine, Krista L.
影响因子：
8.8
作者：
Sellares, J.;de Freitas, D. G.;Halloran, P. F.
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Halloran, P. F.
影响因子：
8.8
作者：
Einecke, G.;Sis, B.;Halloran, P. F.
通讯作者：
Halloran, P. F.
影响因子：
8.8
作者：
Amer, H.;Fidler, M. E.;Cosio, F. G.
通讯作者：
Cosio, F. G.
影响因子：
3.1
作者：
Naik, Abhijit S.;Zhong, Yingchao;Schaubel, Douglas E.
通讯作者：
Schaubel, Douglas E.