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尿标志物的上调可预测IgA肾病的预后,但其预测价值受类固醇和硫唑嘌呤治疗的影响。

Up-regulation of urinary markers predict outcome in IgA nephropathy but their predictive value is influenced by treatment with steroids and azathioprine.

作者信息

Stangou Maria, Papagianni Aikaterini, Bantis Christos, Moisiadis Dimitrios, Kasimatis Stratis, Spartalis Michael, Pantzaki Afroditi, Efstratiadis George, Memmos Dimitrios

出版信息

Clin Nephrol. 2013 Sep;80(3):203-10. doi: 10.5414/CN107836.

DOI:10.5414/CN107836
PMID:23611517
Abstract

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-1β, -2, -4, -5, -6, -10, -12 and -17, INF-γ 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 RAASinhibitors + 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-1β, MCP-1, IL-17, INF-γ, IL-6 and IL-10). Serum creatinine at time of diagnosis had significant correlation with proteinuria (p = 0.02), urinary levels of IL-1β (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 + aza may exert their beneficial effect through suppression of the production or activation of most cytokines.

摘要

目的

类固醇和免疫抑制剂可延缓IgA肾病患者肾功能的进展,但它们对局部细胞因子的可能影响尚未得到研究。

材料与方法

使用牛津分类系统对53例IgA肾病患者(男/女35/18,年龄40.5岁(17 - 65岁))的组织学进行评估。随后,在肾活检当天采集的晨尿样本中,通过多重细胞因子检测法测定白细胞介素-1β、-2、-4、-5、-6、-10、-12和-17、干扰素-γ和单核细胞趋化蛋白-1。在接受6个月的肾素-血管紧张素-醛固酮系统抑制剂+鱼油(FO)治疗后,53例患者中的35例(A组)有反应并继续接受相同治疗,而在18例无反应的患者(B组)中,加用了类固醇+硫唑嘌呤。

结果

毛细血管内增生的存在与促炎和促纤维化细胞因子(白细胞介素-1β、单核细胞趋化蛋白-1、白细胞介素-17、干扰素-γ、白细胞介素-6和白细胞介素-10)的尿排泄显著相关。诊断时的血清肌酐与蛋白尿(p = 0.02)、尿白细胞介素-1β水平(p = 0.03)、白细胞介素-2水平(p = 0.01)和单核细胞趋化蛋白-1水平(p = 0.03)显著相关。A组的肾小球滤过率从65±29降至57±34 ml/分钟,p = 0.005,而B组患者的肾小球滤过率保持稳定(从63±24降至61±30 ml/分钟,p = 无显著性差异)。尿液中大多数检测到的细胞因子可预测A组患者肾功能的恶化,但白细胞介素-6的尿排泄似乎可预测两组患者的肾功能结局。

结论

IgA肾病患者尿液中可排出多种细胞因子,其水平可预测疾病的结局。类固醇+硫唑嘌呤可能通过抑制大多数细胞因子的产生或激活发挥有益作用。

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