{"title":"将 RHAMM 升高作为预测 2 型糖尿病患者糖尿病肾病的生物标志物。","authors":"Bingxue Qi, Yan Lou, Yongyue Zhu, Yang Chen, Shixin Yang, Fanjie Meng, Zhuo Pan, Shuangshuang Liu, Guanchi Yan, Xiaodan Lu, Li-Hao Huang","doi":"10.1093/ckj/sfae196","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Diabetic kidney disease (DKD) poses a significant challenge globally as a complication of diabetes. Hyaluronan (HA), a critical non-sulfated glycosaminoglycan in the extracellular matrix, plays a pivotal role in the progression of DKD. This study assesses the predictive significance of HA's corresponding receptor, RHAMM (receptor for HA-mediated motility), in DKD pathogenesis in type 2 diabetes (T2DM) patients.</p><p><strong>Methods: </strong>Enzyme-linked immunosorbent assays were utilized to measure plasma and urine levels of HA, CD44 and RHAMM in 99 diabetic patients. Immunohistochemistry staining was employed to examine HA deposition, CD44 and RHAMM expressions from 18 biopsy-proven DKD patients. Spearman correlation analysis, linear regression and receiver operating characteristic (ROC) analysis were conducted to establish associations between plasma HA, CD44 and RHAMM levels, and clinical parameters in DKD patients with T2DM.</p><p><strong>Results: </strong>Elevated plasma and urine HA, CD44 and RHAMM levels were notably observed in the severe renal dysfunction group. Plasma RHAMM exhibited positive correlations with HA (r = 0.616, <i>P</i> < .001) and CD44 (r = 0.220, <i>P</i> < .001), and a negative correlation with estimated glomerular filtration rate (eGFR) (r = -0.618, <i>P</i> < .001). After adjusting for other potential predictors, plasma RHAMM emerged as an independent predictor of declining eGFR (β = -0.160, <i>P</i> < .05). Increased HA, CD44 and RHAMM levels in kidney biopsies of DKD patients were closely associated with heightened kidney injury. The ROC curve analysis highlighted an area under the curve (AUC) of 0.876 for plasma RHAMM, indicating superior diagnostic efficacy compared to CD44 in predicting DKD pathogenesis. The combined AUC of 0.968 for plasma RHAMM, HA and CD44 also suggested even greater diagnostic potential for DKD pathogenesis.</p><p><strong>Conclusion: </strong>These findings provide initial evidence that elevated RHAMM levels predict DKD pathogenesis in T2DM patients. The formation of a triple complex involving HA, CD44 and RHAMM on the cell surface shows promise as a targetable biomarker for early intervention to mitigate severe renal dysfunctions.</p>","PeriodicalId":10435,"journal":{"name":"Clinical Kidney Journal","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267228/pdf/","citationCount":"0","resultStr":"{\"title\":\"Elevated RHAMM as a biomarker for predicting diabetic kidney disease in patients with type 2 diabetes.\",\"authors\":\"Bingxue Qi, Yan Lou, Yongyue Zhu, Yang Chen, Shixin Yang, Fanjie Meng, Zhuo Pan, Shuangshuang Liu, Guanchi Yan, Xiaodan Lu, Li-Hao Huang\",\"doi\":\"10.1093/ckj/sfae196\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Diabetic kidney disease (DKD) poses a significant challenge globally as a complication of diabetes. Hyaluronan (HA), a critical non-sulfated glycosaminoglycan in the extracellular matrix, plays a pivotal role in the progression of DKD. This study assesses the predictive significance of HA's corresponding receptor, RHAMM (receptor for HA-mediated motility), in DKD pathogenesis in type 2 diabetes (T2DM) patients.</p><p><strong>Methods: </strong>Enzyme-linked immunosorbent assays were utilized to measure plasma and urine levels of HA, CD44 and RHAMM in 99 diabetic patients. Immunohistochemistry staining was employed to examine HA deposition, CD44 and RHAMM expressions from 18 biopsy-proven DKD patients. Spearman correlation analysis, linear regression and receiver operating characteristic (ROC) analysis were conducted to establish associations between plasma HA, CD44 and RHAMM levels, and clinical parameters in DKD patients with T2DM.</p><p><strong>Results: </strong>Elevated plasma and urine HA, CD44 and RHAMM levels were notably observed in the severe renal dysfunction group. Plasma RHAMM exhibited positive correlations with HA (r = 0.616, <i>P</i> < .001) and CD44 (r = 0.220, <i>P</i> < .001), and a negative correlation with estimated glomerular filtration rate (eGFR) (r = -0.618, <i>P</i> < .001). After adjusting for other potential predictors, plasma RHAMM emerged as an independent predictor of declining eGFR (β = -0.160, <i>P</i> < .05). Increased HA, CD44 and RHAMM levels in kidney biopsies of DKD patients were closely associated with heightened kidney injury. The ROC curve analysis highlighted an area under the curve (AUC) of 0.876 for plasma RHAMM, indicating superior diagnostic efficacy compared to CD44 in predicting DKD pathogenesis. The combined AUC of 0.968 for plasma RHAMM, HA and CD44 also suggested even greater diagnostic potential for DKD pathogenesis.</p><p><strong>Conclusion: </strong>These findings provide initial evidence that elevated RHAMM levels predict DKD pathogenesis in T2DM patients. The formation of a triple complex involving HA, CD44 and RHAMM on the cell surface shows promise as a targetable biomarker for early intervention to mitigate severe renal dysfunctions.</p>\",\"PeriodicalId\":10435,\"journal\":{\"name\":\"Clinical Kidney Journal\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-07-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267228/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Kidney Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/ckj/sfae196\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/7/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Kidney Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/ckj/sfae196","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:糖尿病肾病(DKD)是糖尿病的一种并发症,在全球范围内构成了重大挑战。透明质酸(HA)是细胞外基质中的一种重要的非硫酸化糖胺聚糖,在 DKD 的进展中起着关键作用。本研究评估了HA的相应受体RHAMM(HA介导的运动受体)在2型糖尿病(T2DM)患者DKD发病机制中的预测意义:方法:利用酶联免疫吸附试验测定 99 名糖尿病患者血浆和尿液中的 HA、CD44 和 RHAMM 水平。免疫组化染色法检测了 18 例活检证实的 DKD 患者的 HA 沉积、CD44 和 RHAMM 表达。通过斯皮尔曼相关分析、线性回归和接收器操作特征(ROC)分析,确定了血浆 HA、CD44 和 RHAMM 水平与 T2DM DKD 患者临床参数之间的关系:结果:在严重肾功能不全组中明显观察到血浆和尿液中 HA、CD44 和 RHAMM 水平升高。血浆 RHAMM 与 HA 呈正相关(r = 0.616,P P P P 结论:这些发现提供了初步证据,证明 RHAMM 水平升高可预测 T2DM 患者 DKD 的发病机制。细胞表面形成的涉及 HA、CD44 和 RHAMM 的三重复合物有望成为早期干预以缓解严重肾功能障碍的目标生物标志物。
Elevated RHAMM as a biomarker for predicting diabetic kidney disease in patients with type 2 diabetes.
Background: Diabetic kidney disease (DKD) poses a significant challenge globally as a complication of diabetes. Hyaluronan (HA), a critical non-sulfated glycosaminoglycan in the extracellular matrix, plays a pivotal role in the progression of DKD. This study assesses the predictive significance of HA's corresponding receptor, RHAMM (receptor for HA-mediated motility), in DKD pathogenesis in type 2 diabetes (T2DM) patients.
Methods: Enzyme-linked immunosorbent assays were utilized to measure plasma and urine levels of HA, CD44 and RHAMM in 99 diabetic patients. Immunohistochemistry staining was employed to examine HA deposition, CD44 and RHAMM expressions from 18 biopsy-proven DKD patients. Spearman correlation analysis, linear regression and receiver operating characteristic (ROC) analysis were conducted to establish associations between plasma HA, CD44 and RHAMM levels, and clinical parameters in DKD patients with T2DM.
Results: Elevated plasma and urine HA, CD44 and RHAMM levels were notably observed in the severe renal dysfunction group. Plasma RHAMM exhibited positive correlations with HA (r = 0.616, P < .001) and CD44 (r = 0.220, P < .001), and a negative correlation with estimated glomerular filtration rate (eGFR) (r = -0.618, P < .001). After adjusting for other potential predictors, plasma RHAMM emerged as an independent predictor of declining eGFR (β = -0.160, P < .05). Increased HA, CD44 and RHAMM levels in kidney biopsies of DKD patients were closely associated with heightened kidney injury. The ROC curve analysis highlighted an area under the curve (AUC) of 0.876 for plasma RHAMM, indicating superior diagnostic efficacy compared to CD44 in predicting DKD pathogenesis. The combined AUC of 0.968 for plasma RHAMM, HA and CD44 also suggested even greater diagnostic potential for DKD pathogenesis.
Conclusion: These findings provide initial evidence that elevated RHAMM levels predict DKD pathogenesis in T2DM patients. The formation of a triple complex involving HA, CD44 and RHAMM on the cell surface shows promise as a targetable biomarker for early intervention to mitigate severe renal dysfunctions.
期刊介绍:
About the Journal
Clinical Kidney Journal: Clinical and Translational Nephrology (ckj), an official journal of the ERA-EDTA (European Renal Association-European Dialysis and Transplant Association), is a fully open access, online only journal publishing bimonthly. The journal is an essential educational and training resource integrating clinical, translational and educational research into clinical practice. ckj aims to contribute to a translational research culture among nephrologists and kidney pathologists that helps close the gap between basic researchers and practicing clinicians and promote sorely needed innovation in the Nephrology field. All research articles in this journal have undergone peer review.