ArticleInternational journal of general medicine2023
Nicotinamide N-Methyl Transferase as a Predictive Marker of Tubular Fibrosis in CKD.
Article in International journal of general medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Identification of shared diagnostic biomarkers and molecular pathways between chronic kidney disease and renal cell carcinoma using transcriptomics and machine learning.Translational cancer research · 2026Article
- Structure-Based Drug Discovery of Non-SAM-Mimetic Bisubstrate Inhibitors against NicotinamideACS medicinal chemistry letters · 2026Article
- Article
- Advancements in the non-invasive diagnosis of renal fibrosis.Frontiers in medicine · 2025Review
- Knockdown of nicotinamide N-methyltransferase ameliorates renal fibrosis caused by ischemia-reperfusion injury and remodels sphingosine metabolism.Clinical and experimental nephrology · 2024Article
- Exploring NNMT: from metabolic pathways to therapeutic targets.Archives of pharmacal research · 2024Review
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Authors and funding
12 authors.
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Abstract
Purpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD. Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor. Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β1 were decreased compared with UUO (P < 0.05). Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.
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