Renal expression of advanced oxidative protein products predicts progression of renal fibrosis in patients with IgA nephropathy
Renal expression of advanced oxidative protein products predicts progression of renal fibrosis in patients with IgA nephropathy
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晚期氧化蛋白产物的肾脏表达预测 IgA 肾病患者肾纤维化的进展
DOI：
10.1038/labinvest.2014.90
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发表时间：
2014-09-01
影响因子：
5
通讯作者：
Hou, Fan F.
中科院分区：
文献类型：
--
作者：
Wang, Jun;Liang, Min;Hou, Fan F.
预测IgA肾病（IgAN）的疾病进展风险仍然是一个挑战。本研究旨在验证晚期氧化蛋白产物（AOPPs）的肾脏积聚是IgAN肾脏进展的早期预测因子的假设。这是一项单中心前瞻性队列研究。入选100例IgAN患者，eGFR bb0 80 ml/min/1.73 m(2)。77例患者平均随访4.2年，30例患者在诊断后平均42个月接受重复肾活检。结果是在随访期间肾纤维化进展和CKD快速进展（bbb50 ml/min/1.73 m(2)/年）。AOPPs的免疫反应性主要在小管上皮细胞中检测到，并与tgf - β 1和血管紧张素II的表达共定位。诊断时AOPPs的肾脏染色评分与组织细胞炎症水平相关。在随访期间，AOPPs的积累，特别是在间质浸润细胞中，与eGFR的变化呈负相关；诊断时表达评分大于中位数的患者，eGFR快速下降的发生率明显高于小于或等于中位数的患者。对于接受重复肾活检的患者，诊断时肾脏AOPP水平大于中位数与重复活检时肾脏纤维化指数增加相关。多因素调整后，肾脏AOPP表达是肾纤维化进展和eGFR快速下降的独立预测因子。综上所述，这些结果表明肾脏AOPPs可能是早期IgAN患者肾脏进展的预测因子，在诊断时可检测到。
Predicting the risk of disease progression in IgA nephropathy (IgAN) remains a challenge. This study was conducted to test the hypothesis that renal accumulation of advanced oxidized protein products (AOPPs) is an early predictor for renal progression in IgAN. This was a single-center prospective cohort study. One hundred IgAN patients with eGFR > 80 ml/min/1.73 m(2) were enrolled. Seventy-seven patients were followed for a mean of 4.2 years, and 30 patients received repeat renal biopsy at a mean of 42 months after diagnosis. The outcomes were the progression of renal fibrosis and rapid progression of CKD (> 5 ml/min/1.73 m(2)/year) during follow-up. Immunoreactivity of AOPPs was detected predominantly in tubular epithelial cells and co-localized with expression of TGF-beta 1 and angiotensin II. Renal staining score of AOPPs at diagnosis was associated with the level of tissue cellular inflammation. Accumulation of AOPPs, particularly in interstitial-infiltrating cells, was negatively correlated with changes of eGFR during follow-up; those with expression scores greater than the median at diagnosis had significantly higher incidences of rapid decline of eGFR compared with those with the score less than or equal to the median. For patients who received repeat renal biopsy, renal AOPP levels greater than the median at diagnosis were associated with increase in renal fibrosis index at repeat biopsy. After multivariate adjustment, renal AOPP expression was an independent predictor for progression of renal fibrosis and rapid decline of eGFR. Taken together, these results demonstrate that renal AOPPs might be a predictor, detectable at the time of diagnosis, for renal progression in patients with early stage IgAN.