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.
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.
[http://dx.doi.org/10.5551/jat.RV17023] [PMID: 29998913]
[http://dx.doi.org/10.1016/j.mce.2015.05.003] [PMID: 25958041]
[http://dx.doi.org/10.1038/s41419-021-03850-1] [PMID: 34083513]
[http://dx.doi.org/10.1016/S1388-1981(99)00154-7] [PMID: 10570239]
[http://dx.doi.org/10.1172/JCI34750] [PMID: 18551191]
[http://dx.doi.org/10.1038/nrd2589] [PMID: 18511927]
[http://dx.doi.org/10.1016/j.gene.2018.07.035] [PMID: 30021130]
[http://dx.doi.org/10.1172/jci.insight.141814] [PMID: 33690220]
[http://dx.doi.org/10.1016/j.diabres.2010.11.011] [PMID: 21176857]
[http://dx.doi.org/10.1096/fj.09-134882] [PMID: 19625659]
[http://dx.doi.org/10.1161/ATVBAHA.113.301588] [PMID: 23968980]
[http://dx.doi.org/10.1016/j.abb.2022.109347] [PMID: 35809639]
[http://dx.doi.org/10.1038/nrendo.2015.122] [PMID: 26260145]
[http://dx.doi.org/10.1371/journal.pone.0027356] [PMID: 22102888]
[http://dx.doi.org/10.2337/dc08-1333] [PMID: 18931100]
[http://dx.doi.org/10.1155/2018/4578140] [PMID: 29992142]
[http://dx.doi.org/10.4093/dmj.2019.0221] [PMID: 32662255]
[http://dx.doi.org/10.1111/jcmm.14512] [PMID: 31286669]
[http://dx.doi.org/10.1038/s41598-018-34902-w] [PMID: 30401801]
[http://dx.doi.org/10.7150/thno.63735] [PMID: 34987648]
[http://dx.doi.org/10.3389/fimmu.2020.566535] [PMID: 33101287]