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肾小球糖皮质激素受体表达与 IgA 肾病对皮质类固醇治疗反应的关系。

The Association of Glomerular Glucocorticoid Receptor Expression with Responsiveness to Corticosteroid Treatment in IgA Nephropathy.

机构信息

Department of Internal Medicine, Hangang Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Republic of Korea.

Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, Republic of Korea.

出版信息

Am J Nephrol. 2019;50(3):187-195. doi: 10.1159/000502327. Epub 2019 Aug 13.

Abstract

BACKGROUND

Corticosteroids can be used to treat IgA nephropathy (IgAN). However, responsiveness to these drugs is highly variable and unpredictable. Corticosteroids act by binding glucocorticoid receptors (GCRs). Therefore, we evaluated the association between GCR expression and responsiveness to corticosteroid treatment in IgAN.

METHODS

We screened 78 IgAN patients receiving steroid treatment between 2010 and 2016. Of these, 33 patients met study inclusion criteria. Glomerular GCR expression was assessed by real-time polymerase chain reaction. Complete remission (CR) and partial remission (PR) were defined as a spot urine protein-to-creatinine ratio (UPCR) of <0.3 g/g and a ≥50% reduction of proteinuria from baseline along with UPCR of ≥0.3 g/g, respectively. Disease progression was defined as a ≥30% decrease in estimated glomerular filtration rate (eGFR) from baseline.

RESULTS

The mean age of study patients was 43.9 ± 11.6 years (25 males and 8 females). All 33 patients responded to steroid treatment; CR and PR occurred in 14 (42.4%) and 18 (54.5%) patients, respectively. One patient did not achieve PR, but proteinuria was decreased after treatment. There were no significant differences in baseline eGFR and proteinuria between CR and non-CR groups. GCR mRNA expression was significantly higher in the CR group compared to that in the non-CR group. Immunohistochemistry confirmed higher GCR expression in the CR group. During a median follow-up of 20.6 months, 1 (7.1%) patient in the CR group had disease progression, as compared to 8 (42.1%) patients in non-CR group (p = 0.03).

CONCLUSION

This study suggests that responsiveness to corticosteroid may differ depending on the degree of glomerular GCR expression in IgAN.

摘要

背景

皮质类固醇可用于治疗 IgA 肾病(IgAN)。然而,对这些药物的反应性高度可变且不可预测。皮质类固醇通过结合糖皮质激素受体(GCR)起作用。因此,我们评估了 GCR 表达与 IgAN 对皮质类固醇治疗反应之间的关系。

方法

我们筛选了 2010 年至 2016 年间接受类固醇治疗的 78 例 IgAN 患者。其中,33 例患者符合研究纳入标准。通过实时聚合酶链反应评估肾小球 GCR 表达。完全缓解(CR)和部分缓解(PR)定义为尿蛋白与肌酐比(UPCR)<0.3 g/g 和蛋白尿较基线下降≥50%且 UPCR≥0.3 g/g。疾病进展定义为估计肾小球滤过率(eGFR)自基线下降≥30%。

结果

研究患者的平均年龄为 43.9±11.6 岁(25 名男性和 8 名女性)。所有 33 例患者均对类固醇治疗有反应;CR 和 PR 分别发生在 14 例(42.4%)和 18 例(54.5%)患者中。1 例患者未达到 PR,但治疗后蛋白尿减少。CR 组和非 CR 组之间的基线 eGFR 和蛋白尿无显著差异。CR 组的 GCR mRNA 表达明显高于非 CR 组。免疫组化证实 CR 组的 GCR 表达更高。在中位数为 20.6 个月的随访期间,CR 组中有 1 例(7.1%)患者发生疾病进展,而非 CR 组中有 8 例(42.1%)患者发生疾病进展(p=0.03)。

结论

本研究表明,IgAN 患者对皮质类固醇的反应性可能取决于肾小球 GCR 表达的程度。

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