白蛋白尿和非白蛋白尿型糖尿病肾病患者近端肾小管损伤、炎症和纤维化的尿液生物标志物评估
Evaluation of Urinary Biomarkers of Proximal Tubular Injury, Inflammation, and Fibrosis in Patients With Albuminuric and Nonalbuminuric Diabetic Kidney Disease.
作者信息
Phanish Mysore K, Chapman Andrew N, Yates Sarah, Price Robert, Hendry Bruce M, Roderick Paul J, Dockrell Mark E C
机构信息
South West Thames Institute for Renal Research, Renal Unit, St Helier Hospital, Carshalton, London, UK.
Renal Unit, Epsom and St Helier University Hospitals National Health Service Trust, St Helier Hospital, Carshalton, London, UK.
出版信息
Kidney Int Rep. 2021 Feb 2;6(5):1355-1367. doi: 10.1016/j.ekir.2021.01.012. eCollection 2021 May.
INTRODUCTION
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.
METHODS
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.
RESULTS
In the albumin/creatinine ratio (ACR) <3 cohort, the only biomarker significantly associated with estimated glomerular filtration rate < 60 ml/min was -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.
CONCLUSION
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. -acetyl-β-d-glucosaminidase demonstrated a significant association with an estimated glomerular filtration rate < 60 ml/min in the ACR <3 cohort.
引言
蛋白尿和非蛋白尿途径均与糖尿病肾病有关。近端小管和炎症在这些过程中起重要作用。需要能够检测早期肾脏损伤并预测疾病进展的尿液生物标志物。
方法
对400例糖尿病患者在基线时测量了9种尿液生物标志物。进行相关性分析、多变量逻辑回归分析和线性回归分析，以评估生物标志物与慢性肾脏病及其进展的关联。
结果
在白蛋白/肌酐比值（ACR）<3的队列中，唯一与估计肾小球滤过率<60 ml/分钟显著相关的生物标志物是N-乙酰-β-D-氨基葡萄糖苷酶。在该队列中，ACR与单核细胞趋化蛋白1（MCP1）的组合与2期慢性肾脏病显著相关。逻辑模型显示，在所有蛋白尿水平的患者中，ACR、视黄醇结合蛋白（RBP）和MCP1均与疾病进展有关。在ACR<3的队列中，一个包含MCP1、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进展至3/4期慢性肾脏病显著相关。线性混合模型回归分析表明，MCP1、RBP和ACR是与进展至3期或更严重阶段相关的重要蛋白，而在ACR<3的队列中，MCP1是唯一显著的生物标志物。生存时间和Cox比例风险模型证实了ACR、RBP和MCP1进展的显著风险比，ACR、RBP和MCP1生物标志物分位数之间存在显著差异。
结论
在这项对尿液生物标志物进行单次基线测量的糖尿病患者研究中，在所有蛋白尿水平上，白蛋白、RBP和MCP1均与慢性肾脏病进展显著相关。炎症细胞因子、中性粒细胞明胶酶相关脂质运载蛋白和MCP1与无蛋白尿患者的疾病进展有关。在ACR<3的队列中，N-乙酰-β-D-氨基葡萄糖苷酶与估计肾小球滤过率<60 ml/分钟显著相关。
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