Tanaka Marenao, Sato Tatsuya, Gohda Tomohito, Kamei Nozomu, Murakoshi Maki, Ishiwata Erika, Endo Keisuke, Kawaharata Wataru, Aida Hiroki, Nakata Kei, Akiyama Yukinori, Kubota Mitsunobu, Sanuki Michiyoshi, Suzuki Toru, Suzuki Yusuke, Furuhashi Masato
Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Tanaka Medical Clinic, Yoichi, Japan.
J Diabetes Investig. 2025 Apr;16(4):670-679. doi: 10.1111/jdi.14388. Epub 2024 Dec 26.
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.
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).
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.
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.
目的/引言：脂肪酸结合蛋白（FABP）4作为一种由脂肪细胞、巨噬细胞和毛细血管内皮细胞分泌的脂肪因子，在受损的肾小球细胞中表达。据报道，尿（U-）FABP4在几种肾小球疾病中与肾功能不全和蛋白尿相关。然而，U-FABP4在糖尿病肾病（DKD）中的临床意义仍未确定。
对DKD患者和非肥胖糖尿病小鼠（KK-Ta/Akita小鼠）的肾脏进行FABP4和FABP1（肝型FABP，一种已确立的近端肾小管损伤生物标志物）的免疫组织学分析。还在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之间的关联。
在糖尿病患者和糖尿病小鼠中，FABP4除了在肾小管周围毛细血管中表达外，还在伴有内质网应激标志物增加的受损肾小球中表达，而FABP1主要在近端肾小管中表达。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水平相互独立相关，且两者水平均与估计肾小球滤过率（eGFR）和尿白蛋白与肌酐比值（UACR）独立相关。
来自伴有内质网应激增加的受损肾小球的FABP4尿水平与eGFR和UACR独立相关，提示其可能是糖尿病患者肾小球损伤的一个有前景的生物标志物。
