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2型糖尿病合并不同表型慢性肾脏病患者肾小管损伤和肾纤维化的尿液标志物

Urinary Markers of Tubular Injury and Renal Fibrosis in Patients with Type 2 Diabetes and Different Phenotypes of Chronic Kidney Disease.

作者信息

Korbut Anton I, Romanov Vyacheslav V, Klimontov Vadim V

机构信息

Research Institute of Clinical and Experimental Lymphology-Branch of the Institute of Cytology and Genetics Siberian Branch of Russian Academy of Sciences (RICEL-Branch of IC&G SB RAS), 630060 Novosibirsk, Russia.

出版信息

Life (Basel). 2023 Jan 27;13(2):343. doi: 10.3390/life13020343.

Abstract

This study assessed the urinary excretion of markers and mediators of tubular injury and renal fibrosis in patients with type 2 diabetes (T2D) and non-albuminuric and albuminuric patterns of chronic kidney disease (CKD). One hundred and forty patients with long-term T2D and different patterns of CKD and twenty non-diabetic individuals were included. Urinary retinol-binding protein 4 (RBP-4), glutathione-S-transferase α and π (GST-α and GST-π), transforming growth factor β (TGF-β), type I and type IV collagen (Col1 and Col4), bone morphogenic protein 7 (BMP-7), and hepatocyte growth factor (HGF) were assessed by ELISA. Patients with T2D demonstrated increased urinary excretion of RBP-4, GST-π, Col4, BMP-7, and HGF (all < 0.05 vs. control). The excretion of RBP-4, GST-π, Col1, and Col4 was increased in patients with elevated albumin-to-creatinine ratio (UACR; all < 0.05 vs. control), while BMP-7 and HGF were increased innormoalbuminuric patients also ( < 0.05). Urinary RBP-4, GST-α, Col1, Col4, and HGF correlated positively with UACR; meanwhile, no correlations with glomerular filtration rate were found. The results demonstrate that elevated urinary excretions of the markers of tubular injury (RBP-4, GST-π) and renal fibrosis (Col1, Col4), as well as HGF, an antifibrotic regulator, are associated with the albuminuric pattern of CKD in subjects with T2D.

摘要

本研究评估了2型糖尿病(T2D)患者以及慢性肾脏病(CKD)非蛋白尿和蛋白尿模式患者肾小管损伤和肾纤维化标志物及介质的尿排泄情况。纳入了140例长期患T2D且有不同CKD模式的患者以及20例非糖尿病个体。通过酶联免疫吸附测定(ELISA)评估尿视黄醇结合蛋白4(RBP - 4)、谷胱甘肽 - S - 转移酶α和π(GST - α和GST - π)、转化生长因子β(TGF - β)、I型和IV型胶原(Col1和Col4)、骨形态发生蛋白7(BMP - 7)以及肝细胞生长因子(HGF)。T2D患者的RBP - 4、GST - π、Col4、BMP - 7和HGF尿排泄增加(与对照组相比,均P < 0.05)。白蛋白与肌酐比值(UACR)升高的患者,其RBP - 4、GST - π、Col1和Col4排泄增加(与对照组相比,均P < 0.05),而正常蛋白尿患者的BMP - 7和HGF也增加(P < 0.05)。尿RBP - 4、GST - α、Col1、Col4和HGF与UACR呈正相关;同时,未发现与肾小球滤过率相关。结果表明,肾小管损伤标志物(RBP - 4、GST - π)和肾纤维化标志物(Col1、Col4)以及抗纤维化调节因子HGF的尿排泄增加与T2D患者CKD的蛋白尿模式相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1bb/9961033/faad212a58cc/life-13-00343-g001.jpg

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