Chronic humoral rejection of human kidney allografts is associated with MMP-2 accumulation in podocytes and its release in the urine.
Chronic humoral rejection of human kidney allografts is associated with MMP-2 accumulation in podocytes and its release in the urine.
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DOI：
10.1111/j.1600-6143.2010.03290.x
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发表时间：
2010-11
期刊：
影响因子：
--
通讯作者：
Zorn E
中科院分区：
文献类型：
--
作者：
Wong W;DeVito J;Nguyen H;Sarracino D;Porcheray F;Dargon I;Pelle PD;Collins AB;Tolkoff-Rubin N;Smith RN;Colvin R;Zorn E
慢性体液性排斥反应（Chronic humoral rejection，CHR）是肾移植术后晚期移植肾衰竭的重要原因.总的来说，对子宫内膜异位症的病理生理学了解甚少。基质金属蛋白酶-2（MMP-2）是一种IV型胶原酶，在以前的研究中与慢性肾脏疾病和同种异体移植排斥反应有关。我们研究了MMP-2的存在，在同种异体移植活检和尿中的肾移植受者与CHR。MMP-2染色检测足细胞的免疫组化为所有的肾移植患者，但不常见的患者与其他肾脏并发症。尿MMP-2水平在膀胱癌患者（中位数4942 pg/mL，N = 27）中也显著高于非膀胱癌患者（中位数598 pg/mL，N = 65; p < 0.001）。尿MMP-2水平升高与高水平的蛋白尿在膀胱癌和非膀胱癌患者。纵向分析表明，尿液MMP-2的增加与活检记录的CHR的初步诊断一致。使用酶法，我们证明，MMP-2是目前在其活跃的形式在尿中的CHR患者。总体而言，我们的研究结果与MMP-2肾小球损伤以及间质纤维化和肾小管萎缩观察CHR患者。
Chronic humoral rejection (CHR) is an important cause of late graft failures following kidney transplantation. Overall, the pathophysiology of CHR is poorly understood. Matrix metalloproteinase-2 (MMP-2), a type IV collagenase, has been implicated in chronic kidney disease and allograft rejection in previous studies. We examined the presence of MMP-2 in allograft biopsies and in the urine of kidney transplant recipients with CHR. MMP-2 staining was detected by immunohistochemistry in podocytes for all CHR patients but less frequently in patients with other renal complications. Urinary MMP-2 levels were also significantly higher in CHR patients (median 4942 pg/mL, N = 27) compared to non-CHR patients (median 598 pg/mL, N = 65; p < 0.001). Elevated urinary MMP-2 correlated with higher levels of proteinuria in both CHR and non-CHR patients. Longitudinal analysis indicated that increase in urine MMP-2 coincided with initial diagnosis of CHR as documented by the biopsies. Using an enzymatic assay, we demonstrated that MMP-2 was present in its active form in the urine of patients with CHR. Overall, our findings associate MMP-2 with glomerular injury as well as interstitial fibrosis and tubular atrophy observed in patients with CHR.
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