糖尿病肾脏病患者肾脏纤维化与YAP活化水平的相关性分析

Correlation analysis between renal fibrosis and YAP activation levels in patients with diabetic kidney disease

目的探究糖尿病肾脏病(DKD)患者肾组织Yes相关蛋白(YAP)水平与估算肾小球滤过率(eGFR)的相关性。方法选取空军军医大学唐都医院2017年2月至2022年4月经肾活检确诊为DKD的58例患者,按照KDIGO指南慢性肾脏病的eGFR分期标准将患者分为3组:DKD 1期(n=19)、DKD 2期(n=18)和DKD 3期(n=21),另选择8例接受肾肿瘤切除术患者作为对照组。对肾组织进行YAP免疫荧光染色,分析不同分期的DKD患者肾组织YAP表达水平,及其与不同临床指标和病理分级的相关性。结果DKD 1期和对照组患者之间肾脏YAP的表达无统计学差异。与DKD 1期患者相比,DKD 2期患者肾小管上皮细胞中YAP表达增加(P<0.01),且主要分布于细胞质。但是,与DKD 2期患者相比,DKD 3期患者显示出更多的YAP表达和核移位(P<0.01)。重要的是,肾脏YAP水平呈现DKD分期依赖性的点对点增加(P<0.01)。YAP水平与eGFR(r=-0.854,P<0.01)、血肌酐(r=0.849,P<0.01)和胱抑素C(r=0.717,P<0.01)明显相关。此外,肾组织YAP水平与间质纤维化受累范围(r=0.613 vs r=-0.482)、肾小管萎缩受累范围(r=0.633 vs r=-0.542)和间质纤维化和肾小管萎缩评分(r=0.522 vs r=-0.377)的相关性优于eGFR水平。结论DKD患者的肾组织YAP水平关联于eGFR,并且YAP与肾小管间质损害的关联性优于eGFR,YAP的组织学分析可能是DKD肾脏纤维化评估的一种补充方法,有待进一步研究。

Objective To explore the correlation between the level of Yes-associated protein(YAP)and estimated glomerular filtration rate(eGFR)in patients with diabetic kidney disease(DKD).Methods A total of 58 patients diagnosed with DKD by renal biopsy in Tangdu Hospital,Air Force Medical University from February 2017 to April 2022 were selected and divided into 3 groups according to the eGFR staging criteria of chronic kidney disease in KDIGO guidelines:DKD stageⅠ(n=19),DKD stageⅡ(n=18)and DKD stageⅢ(n=21),and 8 patients who underwent nephrectomy were selected as control group.The immunofluorescence staining was performed on renal tissues to analyze the expression level of YAP in DKD patients at different stages and its correlation with different clinical indexes and pathological grading.Results There was no significant difference in the expression of YAP between patients with DKD stageⅠand control group.Compared with patients with DKD stageⅠ,the expression of YAP in renal tubular epithelial cells in patients with DKD stageⅡwas increased(P<0.01),and it was mainly distributed in the cytoplasm.However,compared with patients with DKD stageⅡ,patients with DKD stageⅢshowed more YAP expression and nuclear translocation(P<0.01).Importantly,renal YAP levels showed a DKD stage-dependent and point-to-point increase(P<0.01).The level of YAP was significantly correlated with eGFR(r=-0.854,P<0.01),serum creatinine(r=0.849,P<0.01)and cystatin C(r=0.717,P<0.01).In addition,the correlation between YAP level in renal tissue and the extent of interstitial fibrosis(r=0.613 vs r=-0.482),tubular atrophy(r=0.633 vs r=-0.542)and interstitial fibrosis and tubular atrophy score(r=0.522 vs r=-0.377)was better than that between YAP level and eGFR level.Conclusion The level of YAP in renal tissue of DKD patients is related to eGFR,and the correlation with tubulointerstitial damage is better than that with eGFR.The histological analysis of YAP may be a complementary method for evaluating renal fibrosis in DKD patients,which needs further study.