Urinary fatty acid-binding protein 4 is a promising biomarker for glomerular damage in patients with diabetes mellitus

IF 3.1 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Journal of Diabetes Investigation Pub Date : 2024-12-26 DOI:10.1111/jdi.14388

Marenao Tanaka, Tatsuya Sato, Tomohito Gohda, Nozomu Kamei, Maki Murakoshi, Erika Ishiwata, Keisuke Endo, Wataru Kawaharata, Hiroki Aida, Kei Nakata, Yukinori Akiyama, Mitsunobu Kubota, Michiyoshi Sanuki, Toru Suzuki, Yusuke Suzuki, Masato Furuhashi

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引用次数: 0

Abstract

Aims/Introduction

Fatty acid-binding protein (FABP) 4, which acts as an adipokine secreted by adipocytes, macrophages, and capillary endothelial cells, is expressed in injured glomerular cells. It has been reported that urinary (U-) FABP4 is associated with renal dysfunction and proteinuria in several glomerular kidney diseases. However, the clinical significance of U-FABP4 in diabetic kidney disease (DKD) remains undetermined.

Materials and Methods

Immunohistological analyses of FABP4 and FABP1 (liver-type FABP), an established biomarker for impaired proximal tubules, were performed in the kidneys of patients with DKD and nonobese diabetic mice (KK-Ta/Akita mice). The associations between U-FABP4 and U-FABP1 with kidney function and metabolic indices were also investigated in patients with type 1 diabetes (n = 57, mean age: 61 years) and patients with type 2 diabetes (n = 608, mean age: 65 years).

Results

In both patients with diabetes and diabetic mice, FABP4 was expressed in injured glomeruli with increased markers of endoplasmic reticulum stress in addition to peritubular capillaries, whereas FABP1 was mainly expressed in proximal tubules. Levels of U-FABP4 and U-FABP1 were independently associated with each other, and both levels were independently associated with estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) after adjustment of age, sex, type of diabetes, duration of diabetes, and systolic blood pressure in patients with diabetes.

Conclusions

Urinary level of FABP4 derived from injured glomeruli with increased endoplasmic reticulum stress is independently associated with eGFR and UACR, suggesting a promising biomarker for glomerular damage in patients with diabetes.

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尿脂肪酸结合蛋白4是糖尿病患者肾小球损伤的一个有前景的生物标志物。

目的/简介：脂肪酸结合蛋白（Fatty acid-binding protein， FABP） 4是一种由脂肪细胞、巨噬细胞和毛细血管内皮细胞分泌的脂肪因子，在损伤的肾小球细胞中表达。据报道，尿（U-） FABP4与几种肾小球肾病的肾功能障碍和蛋白尿有关。然而，U-FABP4在糖尿病肾病（DKD）中的临床意义尚未确定。材料和方法：在DKD患者和非肥胖糖尿病小鼠（KK-Ta/秋田小鼠）的肾脏中对FABP4和FABP1（肝脏型FABP）进行免疫组织学分析，FABP4和FABP1是一种已建立的近端小管受损的生物标志物。在1型糖尿病患者（n = 57，平均年龄61岁）和2型糖尿病患者（n = 608，平均年龄65岁）中，研究了U-FABP4和U-FABP1与肾功能和代谢指标的关系。结果：在糖尿病患者和糖尿病小鼠中，除了小管周围毛细血管外，FABP4在损伤的肾小球中表达，内质网应激标志物增加，而FABP1主要在近端小管中表达。U-FABP4和U-FABP1水平相互独立相关，并且在调整糖尿病患者的年龄、性别、糖尿病类型、糖尿病病程和收缩压后，U-FABP4和U-FABP1水平与肾小球滤过率（eGFR）和尿白蛋白与肌酐比（UACR）的估计值独立相关。结论：尿中来源于内质网应激增加的肾小球损伤的FABP4水平与eGFR和UACR独立相关，提示糖尿病患者肾小球损伤的一个有希望的生物标志物。

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 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).