Domingueti Caroline Pereira, Fóscolo Rodrigo Bastos, Reis Janice Sepúlveda, Campos Fernanda Magalhães Freire, Dusse Luci Maria S, Carvalho Maria das Graças, Braga Gomes Karina, Fernandes Ana Paula
Departamento de Analises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de São João Del-Rei, Campus Centro Oeste Dona Lindu, 35501-296 Divinopolis, MG, Brazil.
Departamento de Clínica Médica, Faculdade de Medicina, Universidade Federal de Minas Gerais, 30130-100 Belo Horizonte, MG, Brazil.
J Diabetes Res. 2016;2016:2315260. doi: 10.1155/2016/2315260. Epub 2015 Dec 6.
This study aimed at investigating the association between haemostatic biomarkers, proinflammatory, and anti-inflammatory cytokines with chronic kidney disease in type 1 diabetic patients. Patients were divided into two groups: with nephropathy (albuminuria ≥ 30 mg/g and/or GFR < 60 mL/min/1.73 m(2)), n = 65; and without nephropathy (albuminuria < 30 mg/g and GFR ≥ 60 mL/min/1.73 m(2)), n = 60. INF-γ, IL-6, IL-10, and TNF-α plasma levels were determined by flow cytometry. VWF, ADAMTS13 antigen, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay and ADAMTS13 activity was assessed by fluorescence resonance energy transfer assay. Elevated levels of INF-γ, VWF, ADAMTS13 antigen, D-Dimer, and reduced ADAMTS13 activity/antigen ratio were observed in patients with nephropathy as compared to those without nephropathy (P = 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.). Cytokines and haemostatic biomarkers remained associated with nephropathy after adjustments (use of statin, acetylsalicylic acid, angiotensin converting enzyme inhibitor, and angiotensin antagonist). INF-γ, TNF-α, and IL-10 significantly correlated with haemostatic biomarkers. Inflammatory and hypercoagulability status are associated with nephropathy in type 1 diabetes mellitus and an interrelationship between them may play an important role in pathogenesis of diabetic nephropathy.
本研究旨在调查1型糖尿病患者中止血生物标志物、促炎细胞因子和抗炎细胞因子与慢性肾病之间的关联。患者被分为两组：患有肾病的患者（蛋白尿≥30 mg/g和/或肾小球滤过率<60 mL/min/1.73 m²），n = 65；未患肾病的患者（蛋白尿<30 mg/g且肾小球滤过率≥60 mL/min/1.73 m²），n = 60。通过流式细胞术测定血浆中INF-γ、IL-6、IL-10和TNF-α的水平。通过酶联免疫吸附测定法测定血管性血友病因子（VWF）、含血小板解聚蛋白和金属蛋白酶13（ADAMTS13）抗原以及D-二聚体的血浆水平，并通过荧光共振能量转移测定法评估ADAMTS13的活性。与未患肾病的患者相比，患肾病的患者中观察到INF-γ、VWF、ADAMTS13抗原、D-二聚体水平升高，而ADAMTS13活性/抗原比值降低（分别为P = 0.001、P < 0.001、P < 0.001、P < 0.001和P < 0.001）。在进行调整（使用他汀类药物、乙酰水杨酸、血管紧张素转换酶抑制剂和血管紧张素拮抗剂）后，细胞因子和止血生物标志物仍与肾病相关。INF-γ、TNF-α和IL-10与止血生物标志物显著相关。炎症和高凝状态与1型糖尿病肾病相关，它们之间的相互关系可能在糖尿病肾病的发病机制中起重要作用。
