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Updated: Jul 4, 2025

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
High-expression of FABP4 in Tubules is a Risk Factor for Poor Prognosis in DKD Patients
Yao Huang1,2, Xinyuan Cui1,2, Zheng Li1,2
1Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
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.
Methods:
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.
Insights
High expression of Fatty Acid Binding Protein 4 (FABP4) in diabetic kidney disease (DKD) is linked to kidney damage and poor prognosis. Increased FABP4 in tubules and inflammatory cells indicates a higher risk of end-stage renal disease (ESRD).
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Imbalanced lipid metabolism contributes to renal tubular injury in diabetic kidney disease (DKD).
- Fatty Acid Binding Protein 4 (FABP4) is implicated in cellular lipid toxicity.
- FABP4 expression in DKD renal tissues and its clinical relevance remain uninvestigated.
Purpose of the Study:
- To investigate FABP4 expression in renal tissues of DKD patients.
- To analyze the correlation of FABP4 with clinical and pathological parameters.
- To evaluate FABP4 as a predictor of prognosis in DKD.
Main Methods:
- Retrospective cohort study of 108 patients (70 DKD, 38 NDKD).
- Measurement of serum/urine FABP4 via ELISA; renal tubulointerstitial FABP4 by immunohistochemistry.
- Assessment of FABP4+ macrophages and statistical analysis including correlation, regression, ROC, and survival curves.
Main Results:
- DKD patients exhibited elevated renal FABP4 expression and ectopic fat deposition.
- Renal tubule FABP4 correlated positively with urine albumin-to-creatinine ratio (UNAG) and end-stage renal disease (ESRD) risk.
- High FABP4 expression in tubules and inflammatory cells independently predicted increased ESRD risk in DKD.
Conclusions:
- Elevated FABP4 expression is integral to the pathogenesis of renal tubular lipid injury in DKD.
- FABP4 serves as a significant biomarker for predicting poor prognosis and ESRD in DKD patients.
- Targeting FABP4 may offer therapeutic potential for DKD management.
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