Association among circulating erythropoietin-producing hepatoma A2, progranulin, and kidney function in individuals with diabetes

IF 3 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Maki Murakoshi, Nozomu Kamei, Kenichiro Abe, Takumi Iwasawa, Kazunori Kato, Marenao Tanaka, Tatsuya Sato, Masato Furuhashi, Mitsunobu Kubota, Michiyoshi Sanuki, Yusuke Suzuki, Tomohito Gohda
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Abstract

Background

Erythropoietin-producing hepatoma A2 (EphA2), a receptor for progranulin (PGRN), which is a growth factor associated with metabolic disorders, is implicated in inflammation and atherosclerotic diseases. Since both EphA2 and PGRN play roles in diabetic kidney disease (DKD) and cardiovascular disease (CVD), this study examined their association with renal function and CVD markers in individuals with diabetes. In addition, the diagnostic value of EphA2 and PGRN in predicting renal impairment was evaluated.

Methods

Circulating EphA2 and PGRN levels were measured using enzyme-linked immunosorbent assay in 735 participants with diabetes. Clinical data, including biometric parameters, physiological measurements, and comorbidities, were collected for analysis.

Results

Both EphA2 and PGRN levels positively correlated with older age, elevated blood pressure, higher urinary albumin-to-creatinine ratio (UACR), and brain natriuretic peptide (BNP) levels but negatively correlated with estimated glomerular filtration rate (eGFR). Multivariate logistic regression analysis revealed that EphA2 was an independent predictor of eGFR <60 mL/min/1.73 m2, even after adjusting for UACR and CVD risk factors and glycated hemoglobin. Although PGRN was also independently associated with eGFR <60 mL/min/1.73 m2, its association was weaker than that of EphA2. Conversely, when UACR ≥30 mg/g was used as the dependent variable, PGRN emerged as a stronger independent determinant than EphA2, even after adjusting for eGFR and CVD risk factors.

Conclusions

EphA2 and PGRN levels are significantly associated with renal function in individuals with diabetes. These findings suggest that EphA2 and PGRN could serve as novel biomarkers for kidney impairment, independent of established CVD markers in this population.

Abstract Image

糖尿病患者循环红细胞生成素产生型肝癌A2、颗粒前蛋白和肾功能之间的关系
背景:促红细胞生成素产生型肝癌A2 (EphA2)是前颗粒蛋白(PGRN)的受体,是一种与代谢紊乱相关的生长因子,与炎症和动脉粥样硬化性疾病有关。由于EphA2和PGRN都在糖尿病肾病(DKD)和心血管疾病(CVD)中发挥作用,本研究探讨了它们与糖尿病患者肾功能和CVD标志物的关系。并评价EphA2和PGRN在预测肾损害中的诊断价值。方法:采用酶联免疫吸附法测定735例糖尿病患者循环EphA2和PGRN水平。收集临床数据,包括生物特征参数、生理测量和合并症,进行分析。结果:EphA2和PGRN水平与年龄、血压升高、尿白蛋白/肌酐比(UACR)和脑钠肽(BNP)水平呈正相关,但与肾小球滤过率(eGFR)呈负相关。多因素logistic回归分析显示EphA2是eGFR 2的独立预测因子,即使在调整了UACR、CVD危险因素和糖化血红蛋白后也是如此。虽然PGRN也与eGFR 2独立相关,但其相关性弱于EphA2。相反,当UACR≥30 mg/g作为因变量时,即使在调整了eGFR和CVD危险因素后,PGRN也比EphA2成为更强的独立决定因素。结论:EphA2和PGRN水平与糖尿病患者肾功能显著相关。这些发现表明EphA2和PGRN可以作为新的肾脏损害生物标志物,独立于该人群中已建立的CVD标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Diabetes Investigation
Journal of Diabetes Investigation ENDOCRINOLOGY & METABOLISM-
CiteScore
6.50
自引率
9.40%
发文量
218
审稿时长
6-12 weeks
期刊介绍: Journal of Diabetes Investigation is your core diabetes journal from Asia; the official journal of the Asian Association for the Study of Diabetes (AASD). The journal publishes original research, country reports, commentaries, reviews, mini-reviews, case reports, letters, as well as editorials and news. Embracing clinical and experimental research in diabetes and related areas, the Journal of Diabetes Investigation includes aspects of prevention, treatment, as well as molecular aspects and pathophysiology. Translational research focused on the exchange of ideas between clinicians and researchers is also welcome. Journal of Diabetes Investigation is indexed by Science Citation Index Expanded (SCIE).
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