ArticleScientific reports2022
The significance of NAD + metabolites and nicotinamide N-methyltransferase in chronic kidney disease.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 48 citations in OpenAlex.
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- Untargeted metabolomics and proteomics reveals cocoa-mediated mitigation of valproic acid-induced dysregulation in a zebrafish model of autism: pilot study.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- NNMT and the methylation sink: integrating metabolism, epigenetics and immunity in cancer.BMC medicine · 2026Review
- 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
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- Identification of Ferroptosis-Related Hub Genes and Immune Infiltration Landscape in Chronic Kidney Disease via Bioinformatics and Experimental Verification.Immunity, inflammation and disease · 2026Article
- NMR-based urinary biomarkers in pediatric primary mitochondrial disorders and chronic kidney disease: shared mitochondrial dysfunction, diverging biosignatures.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Novel applications of SIRT1 in Chronic Kidney Disease.Frontiers in medicine · 2026Review
- Spatial proteomics to discover aging-associated alterations in the renal tubulointerstitium.Clinical proteomics · 2025Article
- Nicotinamide N-Methyltransferase in Cardiovascular Diseases: Metabolic Regulator and Emerging Therapeutic Target.Biomolecules · 2025Review
- NADTrends in molecular medicine · 2025Review
- The role of NADnpj metabolic health and disease · 2025Review
- Multiplatform Metabolomic Profiling of the Unilateral Ureteral Obstruction Murine Model of CKD.International journal of molecular sciences · 2025Article
- Targeted Analysis of Serum and Urinary Metabolites for Early Chronic Kidney Disease.International journal of molecular sciences · 2025Article
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- Whole Blood Metabolomic Profiling of Mice with Tacrolimus-Induced Chronic Nephrotoxicity: NADAntioxidants (Basel, Switzerland) · 2025Article
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Authors and funding
19 authors at 3 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Dysregulation of nicotinamide adenine dinucleotide (NAD +) metabolism contributes to the initiation and progression of age-associated diseases, including chronic kidney disease (CKD). Nicotinamide N-methyltransferase (NNMT), a nicotinamide (NAM) metabolizing enzyme, regulates both NAD + and methionine metabolism. Although NNMT is expressed abundantly in the kidney, its role in CKD and renal fibrosis remains unclear. We generated NNMT-deficient mice and a unilateral ureter obstruction (UUO) model and conducted two clinical studies on human CKD to investigate the role of NNMT in CKD and fibrosis. In UUO, renal NNMT expression and the degraded metabolites of NAM increased, while NAD + and NAD + precursors decreased. NNMT deficiency ameliorated renal fibrosis; mechanistically, it (1) increased the DNA methylation of connective tissue growth factor (CTGF), and (2) improved renal inflammation by increasing renal NAD + and Sirt1 and decreasing NF-κB acetylation. In humans, along with CKD progression, a trend toward a decrease in serum NAD + precursors was observed, while the final NAD + metabolites were accumulated, and the level of eGFR was an independent variable for serum NAM. In addition, NNMT was highly expressed in fibrotic areas of human kidney tissues. In conclusion, increased renal NNMT expression induces NAD + and methionine metabolism perturbation and contributes to renal fibrosis.
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