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犬慢性肾病早期生物标志物:尿中Tamm-Horsfall蛋白、白蛋白、维生素D结合蛋白和视黄醇结合蛋白

Urinary Tamm-Horsfall protein, albumin, vitamin D-binding protein, and retinol-binding protein as early biomarkers of chronic kidney disease in dogs.

作者信息

Chacar Fernanda, Kogika Márcia, Sanches Talita R, Caragelasco Douglas, Martorelli Cínthia, Rodrigues Camila, Capcha Jose Manuel C, Chew Dennis, Andrade Lúcia

机构信息

Department of Veterinary Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil

Department of Veterinary Internal Medicine, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.

出版信息

Physiol Rep. 2017 Jun;5(11). doi: 10.14814/phy2.13262.

Abstract

Proteinuria is a marker and mediator of chronic kidney disease (CKD). In clinical practice, the urinary protein-to-creatinine ratio (UP/C) is of limited usefulness, because it indicates only the magnitude of proteinuria and not the origin of the loss (glomerular or tubular). The complete assessment of proteinuria includes quantitative and qualitative evaluations, both of which are required in order to optimize the therapy. In addition to measuring the UP/C, we performed SDS-PAGE and western blotting to determine the expression of albumin, vitamin D-binding protein (VDBP), retinol-binding protein (RBP), and Tamm-Horsfall protein (THP) in urine samples of 49 dogs: healthy (control) dogs (=9); and dogs with CKD (=40), stratified by stage. In the dogs with stage 3 or 4 CKD, there was a predominance of tubular proteins. Neither VDBP nor RBP was observed in the urine of the control dogs. Among the dogs with stage 1 or 2 CKD, VDBP and RBP were detected in those without proteinuria or with borderline proteinuria. The expression of urinary albumin was significantly higher in the stage 4 group than in any other group (≤0.01). In the stage 4 group, urinary THP was either undetectable or lower than in the control group (≤0.01). In conclusion, urinary VDBP and RBP might act as early markers of kidney injury, and a decrease in urinary THP could be an indicator of CKD progression.

摘要

蛋白尿是慢性肾脏病(CKD)的一个标志物和介导因素。在临床实践中,尿蛋白与肌酐比值(UP/C)的作用有限,因为它仅表明蛋白尿的程度,而不能表明蛋白丢失的来源(肾小球性或肾小管性)。蛋白尿的完整评估包括定量和定性评估,这两者对于优化治疗都是必需的。除了测量UP/C外,我们还进行了十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)和蛋白质印迹法,以测定49只犬尿液样本中白蛋白、维生素D结合蛋白(VDBP)、视黄醇结合蛋白(RBP)和Tamm-Horsfall蛋白(THP)的表达:健康(对照)犬(=9只);以及患有CKD的犬(=40只),按阶段分层。在3期或4期CKD的犬中,以肾小管蛋白为主。对照犬的尿液中未观察到VDBP和RBP。在1期或2期CKD的犬中,在无蛋白尿或临界蛋白尿的犬中检测到了VDBP和RBP。4期组尿白蛋白的表达明显高于其他任何组(≤0.01)。在4期组中,尿THP要么检测不到,要么低于对照组(≤0.01)。总之,尿VDBP和RBP可能作为肾损伤的早期标志物,尿THP的降低可能是CKD进展的一个指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/829e/5471429/cbab67b9a383/PHY2-5-e13262-g001.jpg

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