National Clinical Research Center of Kidney Diseases, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China.
Department of Nephrology,The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Clin J Am Soc Nephrol. 2022 Jul;17(7):986-993. doi: 10.2215/CJN.00350122. Epub 2022 May 18.
There have been only several studies on the correlation between glomerular exostosin expression and membranous lupus nephritis. In this study, we validate the previous findings in Chinese patients with class 5 lupus nephritis.
DESIGN, SETTING, PARTICIPANTS, & MEASURE: One hundred sixty-five patients with class 5 lupus nephritis and varying numbers of control patients were included. Exostosin1/exostosin2 staining was performed by immunohistochemistry, and the staining intensity was quantified using an imaging analysis system. Between-group comparisons were tested for statistical significance using the Pearson chi-squared test, the Fisher exact test, the unpaired test, the Mann-Whitney test, or one-way ANOVA.
In total, 46% of patients with class 5 lupus nephritis, 9% of patients with class 5 + 3/4 lupus nephritis, and none of the other classes of lupus nephritis were exostosin positive. Only three patients were exostosin positive among the 61 patients with other secondary membranous nephropathy. The exostosin-positive rate in nephrotic patients was significantly higher than that in patients without nephrotic syndrome (<0.001), and the exostosin staining intensities of the patients with exostosin-positive class 5 were positively correlated with proteinuria (=0.53; <0.001). Compared with the patients with exostosin-negative cases, the patients with exostosin-positive cases had higher proteinuria levels (3.9 [interquartile range, 2.0-6.3] g/d versus 2.3 [interquartile range, 1.0-3.6] g/d; <0.001); lower scores of activity index (1 [interquartile range, 1-2] versus 2 [interquartile range, 1-3]; =0.001), chronicity index (1 [interquartile range, 0-2] versus 2 [interquartile range, 1-2]; =0.02), and tubular atrophy score (0 [interquartile range, 0-1] versus 1 [interquartile range, 0-1]; =0.008); a higher proportion of extensive subepithelial deposition (62% versus 27%; <0.001); a similar treatment response; and comparable time to kidney end point. Among the 47 patients with class 5 who underwent repeat biopsy, 97% of those with exostosin-negative cases remained negative, whereas 44% of those with exostosin-positive cases were still positive. The rate of histologic transition in the patients with exostosin-negative class 5 was significantly higher than that in the patients with exostosin-positive class 5 (59% versus 22%; =0.03).
Exostosin positivity occurred frequently in patients with class 5 lupus nephritis, and patients with exostosin-positive cases had more severe proteinuria and a lower rate of histologic transition than the exostosin-negative patients.
仅有少数研究探讨了肾小球外生骨蛋白表达与膜性狼疮肾炎之间的相关性。本研究旨在验证外生骨蛋白在中国人 5 型狼疮肾炎患者中的表达。
设计、地点、参与者和方法:纳入 165 例 5 型狼疮肾炎患者及不同数量的对照患者。通过免疫组织化学法检测外生骨蛋白 1/2 的染色情况,并使用图像分析系统定量染色强度。采用 Pearson 卡方检验、Fisher 确切概率法、独立样本 t 检验、Mann-Whitney U 检验或单因素方差分析对组间差异进行统计学分析。
5 型狼疮肾炎患者中,46%为外生骨蛋白阳性,5+3/4 型狼疮肾炎患者中 9%为外生骨蛋白阳性,而其他类型的狼疮肾炎均无阳性表达。在 61 例其他继发性膜性肾病患者中,仅有 3 例为外生骨蛋白阳性。肾病患者的外生骨蛋白阳性率显著高于无肾病综合征患者(<0.001),外生骨蛋白阳性 5 型患者的外生骨蛋白染色强度与蛋白尿呈正相关(=0.53;<0.001)。与外生骨蛋白阴性患者相比,外生骨蛋白阳性患者的蛋白尿水平更高(3.9 [四分位间距 2.0-6.3] g/d 比 2.3 [四分位间距 1.0-3.6] g/d;<0.001),活动指数评分更低(1 [四分位间距 1-2] 比 2 [四分位间距 1-3];=0.001),慢性指数评分更低(1 [四分位间距 0-2] 比 2 [四分位间距 1-2];=0.02),肾小管萎缩评分更低(0 [四分位间距 0-1] 比 1 [四分位间距 0-1];=0.008),广泛的上皮下沉积比例更高(62%比 27%;<0.001),治疗反应相似,肾脏终点事件时间无差异。在 47 例行重复肾活检的 5 型患者中,97%的外生骨蛋白阴性患者仍为阴性,而 44%的外生骨蛋白阳性患者仍为阳性。外生骨蛋白阴性 5 型患者的组织学转换率显著高于外生骨蛋白阳性 5 型患者(59%比 22%;=0.03)。
外生骨蛋白在 5 型狼疮肾炎患者中较常见,外生骨蛋白阳性患者的蛋白尿更严重,组织学转换率更低。