High-expression of FABP4 in Tubules is a Risk Factor for Poor Prognosis in DKD Patients

Yao Huang; Xinyuan Cui; Zheng Li; Shuguang Yuan; Yachun Han; Xiangqing Xu; Xiao Fu; Kewen Shi; Zurong Zhang; Jinying Wei; Shiyu Xia; Yang Xiao; Song Xue; Lin Sun; Hong Liu; Xuejing Zhu

doi:10.2174/0109298673268265231228125431

High-expression of FABP4 in Tubules is a Risk Factor for Poor Prognosis in DKD Patients

Curr Med Chem. 2024 Jan 31. doi: 10.2174/0109298673268265231228125431. Online ahead of print.

Authors

Yao Huang^{1

2}, Xinyuan Cui^{1

2}, Zheng Li^{1

2}, Shuguang Yuan^{1

2}, Yachun Han^{1

2}, Xiangqing Xu^{1

2}, Xiao Fu^{1

2}, Kewen Shi^{1

2}, Zurong Zhang^{1

2}, Jinying Wei^{1

2}, Shiyu Xia^{1

2}, Yang Xiao³, Song Xue^{3

4}, Lin Sun^{1

2}, Hong Liu^{1

2}, Xuejing Zhu^{1

2}

Affiliations

¹ Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
² Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China.
³ National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.
⁴ Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine.

PMID: 38299395
DOI: 10.2174/0109298673268265231228125431

Abstract

Background: Lipid metabolism imbalance is involved in the mechanism of renal tubular injury in diabetic kidney disease (DKD). Fatty acid binding protein 4 (FABP4) has been reported to participate in cellular lipid toxicity. However, the expression of FABP4 in renal tissues of DKD and its correlation with clinical/ pathological parameters and prognosis have not been studied.

Method: A retrospective cohort study was conducted in 108 hospitalized Type 2 diabetes (T2D) patients with renal injury, including 70 with DKD and 38 with NDKD (non-DKD). Clinical features, pathological findings, and follow-up parameters were collected. Serum and urine FABP4 were detected by ELISA. An immunohistochemistry stain was used to determine FABP4 in renal tubulointerstitium. A double immunofluorescence stain was employed to assess FABP4- and CD68-positive macrophages. Correlation analysis, logistic regression models, receiver operating characteristic (ROC), and Kaplan-Meier survival curve were performed for statistical analysis.

Results: DKD patients had increased expression of FABP4 and ectopic fat deposition in tubules. As shown by correlation analyses, FABP4 expression in renal tubules was positively correlated with UNAG (r=0.589, p=0.044) and ESRD (r=0.740, p=0.004). Multivariate regression analysis revealed that UNAG level was correlated with FABP4 expression level above median value (odds ratio:1.154, 95% confidence interval:1.009-1.321, p=0.037). High-expression of FABP4 in renal tubules of DKD was at an increased risk of ESRD. Increased FABP4 expression in inflammatory cells was also associated with ESRD in DKD.

Conclusion: High-expression of FABP4 is involved in the pathogenesis of renal tubular lipid injury and is a risk factor for poor prognosis in DKD patients.

Keywords: Diabetic kidney disease; Fatty acid binding protein 4; Fatty acid binding protein Diabetic kidney disease; Renal tubular injury.