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Background <p>Chronic kidney disease (CKD) is a global public health burden characterized by irreversible renal function loss and progressive fibrosis. Non-invasive biomarkers reflecting intra-renal inflammation and early tubulointerstitial injury remain an unmet clinical need. We combined bioinformatics analysis with clinical validation to characterize two immune-related genes, TNFSF14 and CD40, in CKD progression.</p> Methods <p>Two independent CKD transcriptomic datasets (GSE66494, <i>n</i> = 61; GSE97709, <i>n</i> = 48) were retrieved from the GEO database. Differentially Expressed Genes (DEGs) were screened with FDR adjustment. Clinical validation was performed in 140 CKD patients (KDIGO Stages I–V) and 60 healthy controls. TNFSF14 and CD40 levels were quantified in serum/urine via ELISA, with intra-renal expression assessed via immunofluorescence in 80 biopsy specimens. Multivariable regression was used to evaluate independent predictive value.</p> Results <p>TNFSF14 and CD40 were identified as core hub genes enriched in the TNF signaling pathway. Both markers were significantly elevated in serum/urine of CKD patients (Adjusted <i>P</i> &lt; 0.05), with upregulation localized to renal tubular epithelial cells. Urinary levels increased in a CKD stage-dependent manner, positively correlating with serum creatinine/BUN and inversely with eGFR. Urinary TNFSF14 and CD40 were independent predictors of advanced CKD, with a combined diagnostic model achieving an AUC of 0.892 (95% CI: 0.851–0.933).</p> Conclusions <p>TNFSF14 and CD40 are robust molecular signatures of tubulointerstitial injury, and their urinary levels serve as non-invasive biomarkers for CKD detection and risk stratification.</p>

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Integrated bioinformatics analysis and clinical validation identifies TNFSF14 and CD40 as novel biomarkers for chronic kidney disease progression and tubulointerstitial injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月25日

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  • Xiameng Gu,
  • Yuqing Lu,
  • Haonan Sha,
  • Hanlu Zhang,
  • Hongxin Chen,
  • Mengyue Qiu,
  • Xiaolan Chen

摘要

Background

Chronic kidney disease (CKD) is a global public health burden characterized by irreversible renal function loss and progressive fibrosis. Non-invasive biomarkers reflecting intra-renal inflammation and early tubulointerstitial injury remain an unmet clinical need. We combined bioinformatics analysis with clinical validation to characterize two immune-related genes, TNFSF14 and CD40, in CKD progression.

Methods

Two independent CKD transcriptomic datasets (GSE66494, n = 61; GSE97709, n = 48) were retrieved from the GEO database. Differentially Expressed Genes (DEGs) were screened with FDR adjustment. Clinical validation was performed in 140 CKD patients (KDIGO Stages I–V) and 60 healthy controls. TNFSF14 and CD40 levels were quantified in serum/urine via ELISA, with intra-renal expression assessed via immunofluorescence in 80 biopsy specimens. Multivariable regression was used to evaluate independent predictive value.

Results

TNFSF14 and CD40 were identified as core hub genes enriched in the TNF signaling pathway. Both markers were significantly elevated in serum/urine of CKD patients (Adjusted P < 0.05), with upregulation localized to renal tubular epithelial cells. Urinary levels increased in a CKD stage-dependent manner, positively correlating with serum creatinine/BUN and inversely with eGFR. Urinary TNFSF14 and CD40 were independent predictors of advanced CKD, with a combined diagnostic model achieving an AUC of 0.892 (95% CI: 0.851–0.933).

Conclusions

TNFSF14 and CD40 are robust molecular signatures of tubulointerstitial injury, and their urinary levels serve as non-invasive biomarkers for CKD detection and risk stratification.