Evaluation of Urinary Biomarkers of Proximal Tubular Injury, Inflammation, and Fibrosis in Patients With Albuminuric and Nonalbuminuric Diabetic Kidney Disease.
Evaluation of Urinary Biomarkers of Proximal Tubular Injury, Inflammation, and Fibrosis in Patients With Albuminuric and Nonalbuminuric Diabetic Kidney Disease.
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DOI：
10.1016/j.ekir.2021.01.012
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发表时间：
2021-05
影响因子：
6
通讯作者：
Dockrell MEC
中科院分区：
文献类型：
--
作者：
Phanish MK;Chapman AN;Yates S;Price R;Hendry BM;Roderick PJ;Dockrell MEC
白蛋白尿和非白蛋白尿途径导致糖尿病肾病。近端小管和炎症在这些过程中起重要作用。需要尿生物标志物来检测早期肾损伤和预测进展。在400名糖尿病患者的基线时测量了9种尿液生物标志物。进行相关性和多变量逻辑和线性回归分析，以评估生物标志物与慢性肾脏疾病和进展的相关性。在白蛋白/肌酐比值（ACR）<3的队列中，与估计的肾小球滤过率< 60 ml/min显著相关的唯一生物标志物是N-乙酰-β-d-氨基葡萄糖苷酶。在该队列中，ACR和单核细胞趋化蛋白1（MCP 1）的组合与2期慢性肾脏疾病显著相关。Logistic模型显示，在所有水平的白蛋白尿患者中，ACR、视黄醇结合蛋白（RBP）和MCP 1与疾病进展相关。包括MCP 1、白细胞介素6和中性粒细胞明胶酶相关脂质运载蛋白的模型显示与ACR <3队列中3/4的慢性肾病进展显著相关。线性混合模型回归分析表明，MCP 1、RBP和ACR是与进展至3期或更差相关的重要蛋白质，而MCP 1是ACR <3队列中唯一重要的生物标志物。至事件发生时间和考克斯比例风险模型证实了ACR、RBP和MCP 1进展的显著风险比，ACR、RBP和MCP 1生物标志物的分位数之间存在显著差异。在这项研究中，糖尿病患者的尿生物标志物、白蛋白、RBP和MCP 1的单一基线测量值与所有白蛋白尿水平的慢性肾脏疾病进展显著相关。炎性细胞因子、中性粒细胞明胶酶相关脂质运载蛋白和MCP 1与无白蛋白尿患者的疾病进展相关。在ACR <3的队列中，N-乙酰-β-d-氨基葡萄糖苷酶与估计的肾小球滤过率< 60 ml/min显著相关。
Albuminuric and nonalbuminuric pathways contribute to diabetic kidney disease. Proximal tubule and inflammation play important roles in these processes. Urinary biomarker(s) to detect early kidney damage and predict progression are needed. Nine urinary biomarkers were measured at baseline in 400 patients with diabetes. Correlation and multivariate logistic and linear regression analyses were performed to assess the association of biomarkers with chronic kidney disease and progression. In the albumin/creatinine ratio (ACR) <3 cohort, the only biomarker significantly associated with estimated glomerular filtration rate < 60 ml/min was N-acetyl-β-d-glucosaminidase. A combination of ACR and monocyte chemoattractant protein 1 (MCP1) were significantly associated with stage 2 chronic kidney disease in this cohort. Logistic models showed that in patients with all levels of albuminuria, ACR, retinol binding protein (RBP), and MCP1 were associated with progression. A model including MCP1, interleukin 6, and neutrophil gelatinase-associated lipocalin showed significant association with progression to chronic kidney disease 3/4 in the ACR <3 cohort. Linear mixed-model regression analyses demonstrated MCP1, RBP, and ACR as significant proteins associated with progression to stage 3 or worse, whereas MCP1 was the only significant biomarker in the ACR <3 cohort. Time-to-event and Cox proportional hazard models confirmed significant hazard ratios for progression for ACR, RBP, and MCP1, with significant differences noted between quantiles of biomarkers for ACR, RBP, and MCP1. In this study of diabetic patients with single baseline measurements of urinary biomarkers, albumin, RBP, and MCP1 were significantly associated with chronic kidney disease progression at all levels of albuminuria. Inflammatory cytokines, neutrophil gelatinase-associated lipocalin, and MCP1 were associated with progression in patients without albuminuria. N-acetyl-β-d-glucosaminidase demonstrated a significant association with an estimated glomerular filtration rate < 60 ml/min in the ACR <3 cohort.
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影响因子：
3.4
作者：
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影响因子：
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