Background: Diabetic kidney disease (DKD) is a common and serious complication of diabetes, affecting approximately 40% of patients with the condition. The pathogenesis of DKD is complex, involving multiple processes such as metabolism, inflammation, and fibrosis. Given its increasing incidence and associated mortality, there is an urgent need to identify novel pathogenic genes and therapeutic targets. Methods: This study systematically identified hub DKD-associated genes and their potential molecular mechanisms through bioinformatic analysis. Gene expression datasets from DKD patients and healthy controls were obtained from the GEO database. Hub genes were screened using differential expression analysis, weighted gene co-expression network analysis (WGCNA), LASSO regression, random forest (RF) algorithms, and consensus clustering for DKD patient classification. Additionally, immune cell infiltration analysis was performed on differentially expressed genes to explore the relationship between hub genes and the immune microenvironment. Potential drugs targeting LPL were predicted based on gene-drug interaction analysis. Immunohistochemistry was used to verify the expression of LPL and TNF-α in kidney tissues from patients with varying degrees of DKD severity, as well as their relationship with kidney function impairment. Results: This study revealed that LPL, a lipoprotein metabolism gene, plays a crucial role in DKD, participating in cholesterol and glycerolipid metabolism as well as PPAR signaling. LPL expression was negatively correlated with pro-inflammatory M1 macrophages and various subsets of T cells, including naïve CD4 T cells and gamma delta T cells, while positively correlated with follicular helper T cells, suggesting its immune-regulation effects in DKD progression. Potential LPL-targeting drugs, such as Ibrolipim, anabolic steroid, and acarbose, might mitigate DKD. LPL expression was decreased with DKD severity and was correlated with TNF-α and kidney dysfunction markers, indicating its key role in DKD progression. Conclusion: LPL is a pivotal regulator of lipid metabolism and immune inflammation in DKD. Potential drugs targeting LPL offer new candidates for precision treatment of DKD. These findings lay a theoretical foundation for understanding the molecular mechanisms of DKD and developing LPL-based therapeutic strategies.

Correction on: Dong Q, Xu H, Xu P, Liu J and Shen Z (2025) Bioinformatic analysis identifies LPL as a critical gene in diabetic kidney disease via lipoprotein metabolism. Front. Endocrinol. 16:1620032. doi: 10.3389/fendo.2025.1620032.The Figure 5 caption were in the wrong order in the PDF/HTML version of this paper. The labels for panels (A) and (B) have been swapped. The order has now been corrected. The original version of this article has been updated.Adding/removing text The error made was a directional error in the interpretation of the statistical result for the gene CTNNBIP1.A correction has been made to the section Results -Consensus cluster analysis, Paragraph 2: "There were significant differences in the expression levels of core genes between the two subtypes (Figure 5C,D). Specifically, compared to Cluster B, Cluster A exhibited significantly reduced expression of LPL (P < 0.01) and CTNNBIP1 (p < 0.001), along with lower expression of BCAM. In contrast, Cluster A showed significantly elevated expression of SERPINE2 (p < 0.01) and higher expression of GCNT3." Dong Q, Xu H, Xu P, Liu J and Shen Z Frontiers Media SA 2The original version of this article has been updated.Adding/removing textThe pathway names and their corresponding P-values have been corrected to match the data presented in Table 1.A correction has been made to the section Results -Hub gene enrichment analysis, Paragraph 1:"The results showed that LPL was significantly associated with Cholesterol metabolism (P=0.012), Glycerolipid metabolism (P=0.015) and PPAR signaling pathway (P=0.018, Table 1). These findings suggest that LPL may play a crucial role in lipid metabolism disorders, and through regulating lipid metabolism and inflammatory responses, it could contribute to the progression of DKD."The original version of this article has been updated.