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丝氨酸蛋白酶抑制剂 A3 在大鼠慢性肾脏病(CKD)向急性肾损伤(AKI)转变中的早期识别及其在 CKD 患者识别中的潜力。

SerpinA3 in the Early Recognition of Acute Kidney Injury to Chronic Kidney Disease (CKD) transition in the rat and its Potentiality in the Recognition of Patients with CKD.

机构信息

Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, Mexico.

Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

出版信息

Sci Rep. 2019 Jul 17;9(1):10350. doi: 10.1038/s41598-019-46601-1.

DOI:10.1038/s41598-019-46601-1
PMID:31316093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6637202/
Abstract

Recognizing patients at early phases of chronic kidney disease (CKD) is difficult, and it is even more challenging to predict acute kidney injury (AKI) and its transition to CKD. The gold standard to timely identify renal fibrosis is the kidney biopsy, an invasive procedure not usually performed for this purpose in clinical practice. SerpinA3 was identified by high-resolution-mass-spectrometry in urines from animals with CKD. An early and progressive elevation of urinary SerpinA3 (uSerpinA3) was observed during the AKI to CKD transition together with SerpinA3 relocation from the cytoplasm to the apical tubular membrane in the rat kidney. uSerpinA3/alpha-1-antichymotrypsin was significantly increased in patients with CKD secondary to focal and segmental glomerulosclerosis (FSGS), ANCA associated vasculitis (AAV) and proliferative class III and IV lupus nephritis (LN). uSerpinA3 levels were independently and positively associated with renal fibrosis. In patients with class V LN, uSerpinA3 levels were not different from healthy volunteers. uSerpinA3 was not found in patients with systemic inflammatory diseases without renal dysfunction. Our observations suggest that uSerpinA3 can detect renal fibrosis and inflammation, with a particular potential for the early detection of AKI to CKD transition and for the differentiation among lupus nephritis classes III/IV and V.

摘要

识别慢性肾脏病 (CKD) 的早期阶段的患者很困难,更具挑战性的是预测急性肾损伤 (AKI) 及其向 CKD 的转变。及时识别肾纤维化的金标准是肾活检,这是一种侵入性程序,在临床实践中通常不用于此目的。SerpinA3 是通过高通量质谱在 CKD 动物的尿液中鉴定出来的。在 AKI 向 CKD 转变期间,观察到尿中 SerpinA3 (uSerpinA3) 的早期和进行性升高,同时 SerpinA3 从细胞质重新定位到大鼠肾脏的顶端管状膜。继发于局灶节段性肾小球硬化症 (FSGS)、ANCA 相关性血管炎 (AAV) 和增殖性 III 类和 IV 类狼疮肾炎 (LN) 的 CKD 患者的 uSerpinA3/alpha-1-抗胰蛋白酶显著增加。uSerpinA3 水平与肾纤维化独立且呈正相关。在 V 类 LN 患者中,uSerpinA3 水平与健康志愿者无差异。在无肾功能障碍的系统性炎症性疾病患者中未发现 uSerpinA3。我们的观察表明,uSerpinA3 可以检测肾纤维化和炎症,特别是在早期检测 AKI 向 CKD 转变以及区分 III/IV 类和 V 类狼疮肾炎方面具有特殊潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/0c562ea19b77/41598_2019_46601_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/3b2204859462/41598_2019_46601_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/ab5a997519d0/41598_2019_46601_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/eaf571b4eabd/41598_2019_46601_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/fe57d199d8e2/41598_2019_46601_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/b281fb0894ff/41598_2019_46601_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/0c562ea19b77/41598_2019_46601_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/3b2204859462/41598_2019_46601_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/ab5a997519d0/41598_2019_46601_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/eaf571b4eabd/41598_2019_46601_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/fe57d199d8e2/41598_2019_46601_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/b281fb0894ff/41598_2019_46601_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab55/6637202/0c562ea19b77/41598_2019_46601_Fig6_HTML.jpg

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