Evidence map›Paper›PMID 42033552›Full record

ArticleInternational urology and nephrology2026

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

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

Abstract readValidation Study
In one paragraph

Article in International urology and nephrology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Xiameng Gu *Department of Nephrology, Affiliated Hospital of Nantong University, Jiangsu, 226001, China.
Yuqing Lu *Department of Pediatric Surgery, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
Haonan ShaDepartment of Nephrology, Affiliated Hospital of Nantong University, Jiangsu, 226001, China.
Hanlu ZhangDepartment of Nephrology, Affiliated Hospital of Nantong University, Jiangsu, 226001, China.
Hongxin ChenDepartment of Nephrology, Affiliated Hospital of Nantong University, Jiangsu, 226001, China.
Mengyue QiuDepartment of Nephrology, Affiliated Hospital of Nantong University, Jiangsu, 226001, China.
Xiaolan ChenDepartment of Nephrology, Affiliated Hospital of Nantong University, Jiangsu, 226001, China. chenxl8448@sina.com.

Funding

Science and Technology Project of Nantong City JCZ20066
6 · The paper itself

Abstract

backgroundChronic 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.

methodsTwo 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.

resultsTNFSF14 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).

conclusionsTNFSF14 and CD40 are robust molecular signatures of tubulointerstitial injury, and their urinary levels serve as non-invasive biomarkers for CKD detection and risk stratification.

Indexed as

CD40 AntigensRenal Insufficiency, ChronicTumor Necrosis Factor Ligand Superfamily Member 14AdultBiomarkersComputational BiologyDisease ProgressionFemaleHumansKidney TubulesMaleMiddle AgedNephritis, InterstitialBiomarkersCD40 AntigensTNFSF14 protein, humanTumor Necrosis Factor Ligand Superfamily Member 14BioinformaticsBiomarkerCD40Chronic kidney diseaseRenal fibrosisTNFSF14Tubulointerstitial injuryUrinary biomarkers

Identifiers

PMID42033552
PMCPMC13585850

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.