Epidemiological and transcriptome data identify potential key genes involved in inflammatory response for diabetic nephropathy

The neutrophil percentage-to-albumin ratio (NPAR) is a novel inflammatory marker, and diabetic nephropathy (DN) are linked to inflammation. The primary objective of this investigation was to elucidate the functions and underlying mechanisms of inflammatory response in the development of DN. Epidemiological data from the National Health and Nutrition Examination Survey (NHANES) spanning 2009 to 2018 were utilized to systematically investigate the association between NPAR and DN. Furthermore, transcriptomic data from the Gene Expression Omnibus (GEO) were analyzed using bioinformatics approaches to examine potential functional mechanisms, focusing on gene expression and immune cell infiltration. A significant positive association was observed between NPAR and the risk of DN, as indicated by the multivariate linear regression analysis results [OR 1.62 (95% CI 1.22-2.15) and 2.06 (95% CI 1.53-2.77)]. Subgroup analyses and interaction testing indicated that factors such as age, gender, race, body mass index, smoking status, hypertension, and physical activity did not significantly modify this positive association (p for interaction > 0.05). Data from NHANES showed a non-linear relationship between NPAR and DN was observed, with a calculated inflection point of 1163.64 using a linear regression model. We identified 49 hub gene from transcriptomic data, with DUSP1, CXCR1, and SKIL as key genes in DN progression. The p38MAPK pathway plays a central role in DN development. Resveratrol strongly interacts with DUSP1, curcumin with CXCR1, and genistein with SKIL. The development and progression of DN is significantly influenced by the inflammatory response. NPAR serves as a reliable diagnostic indicator for DN, whereas resveratrol, curcumin, and genistein may have potential value in the treatment of DN.