Up-regulation of urinary markers predict outcome in IgA nephropathy but their predictive value is influenced by treatment with steroids and azathioprine
Up-regulation of urinary markers predict outcome in IgA nephropathy but their predictive value is influenced by treatment with steroids and azathioprine
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DOI：
10.5414/cn107836
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发表时间：
2013-09-01
影响因子：
1.1
通讯作者：
Memmos, Dimitrios
中科院分区：
文献类型：
--
作者：
Stangou, Maria;Papagianni, Aikaterini;Memmos, Dimitrios
目的：类固醇和免疫抑制剂可以延缓 IgAN 肾功能的进展，但尚未研究它们对局部细胞因子的可能影响。材料和方法：使用牛津分类系统对 53 名 IgAN 患者（男/女 35/18，年龄 40.5 岁（17 - 65））的组织学进行评估。随后通过多重细胞因子测定在肾活检当天采集的第一份晨尿样本中测量IL-1β、-2、-4、-5、-6、-10、-12和-17、INF-γ和MCP-1。经过 6 个月的肾素血管紧张素醛固酮系统抑制剂 (RAASi) + 鱼油 (FO) 疗程后，A 组 35/53 名患者有反应并继续接受相同的治疗，而 B 组 18/53 名没有反应的患者添加了类固醇 + 硫唑嘌呤。结果：毛细血管内增殖的存在与尿中促炎和促纤维化细胞因子（IL-1β、MCP-1、IL-17、INF-gamma、IL-6 和 IL-10）的排泄显着相关。诊断时的血清肌酐与蛋白尿 (p = 0.02)、尿中 IL-1β (p = 0.03)、IL-2 (p = 0.01) 和 MCP-1 (p = 0.03) 水平显着相关。 A 组患者的 GFR 从 65 +/- 29 降低至 57 +/- 34 ml/min，p = 0.005，B 组患者保持稳定（GFR 从 63 +/- 24 至 61 +/- 30 ml/min，p = NS）。尿液中检测到的大多数细胞因子预测 A 组患者的肾功能恶化，但尿液中 IL-6 的排泄量似乎可以预测两组患者的肾功能结果。结论：IgAN 患者的尿液中会分泌多种细胞因子，其水平可预测疾病的转归。类固醇+硫唑嘌呤可以通过抑制大多数细胞因子的产生或激活来发挥其有益作用。
Objective: Steroids and immunosuppressants can delay progression of renal function in IgAN, but their possible effect in local cytokines has not been studied. Material and methods: Histology in 53 IgAN patients (M/F 35/18 age 40.5 years (17 - 65)) was evaluated using the Oxford classification system. IL-1 beta, -2, -4, -5, -6, -10, -12 and -17, INF-gamma and MCP-1 were measured subsequently by multiplex cytokine assay in first morning urine samples taken at the day of renal biopsy. After a 6-month course with renin angiotensin aldosterone system inhibitors (RAASi) + fish oils (FO), 35/53 patients, Group A, responded and continued on the same treatment, while in 18/53 who did not respond, Group B, steroids + azathiopine were added. Results: The presence of endocapillary proliferation had significant correlation with the urinary excretion of pro-inflammatory and pro-fibrotic cytokines (IL-1 beta, MCP-1, IL-17, INF-gamma, IL-6 and IL-10). Serum creatinine at time of diagnosis had significant correlation with proteinuria (p = 0.02), urinary levels of IL-1 beta (p = 0.03), IL-2 (p = 0.01) and MCP-1 (p = 0.03). GFR was reduced from 65 +/- 29 to 57 +/- 34 ml/min, p = 0.005 in Group A and remained stable in Group B patients (GFR from 63 +/- 24 to 61 +/- 30 ml/min, p = NS). Most of the measured cytokines in the urine predicted deterioration of renal function in Group A, but the urinary excretion of IL-6 seemed to predict renal function outcome in both groups of patients. Conclusion: Several cytokines are excreted in the urine of patients with IgAN, and their levels predict the outcome of the disease. Steroids + azathioprine may exert their beneficial effect through suppression of the production or activation of most cytokines.