ArticlePloS one2013
Elevated Klotho promoter methylation is associated with severity of chronic kidney disease.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Correlation between SolubleBioMed research international · 2018Pooled it
- Novel insights into the role of the renal interstitial microenvironment in Randall's plaque formation (Review).International journal of molecular medicine · 2026Review
- Epigenetic mechanisms and steroid-resistant nephrotic syndrome: The future potential for SRNS diagnosis.iScience · 2026Review
- Progress in the study of the role of C5a-induced tubular cell senescence in the progression of diabetic kidney disease.Annals of medicine · 2025Review
- Inhibition of epigenetic regulator UHRF1 attenuates renal fibrosis and retains transcription factor Krüppel-like factor 15 expression.Cell death discovery · 2025Article
- Klotho alleviates oxidative stress and mitochondrial dysfunction through the Nrf2/HO-1 pathway, thereby reducing renal senescence induced by calcium oxalate crystals.Urolithiasis · 2025Article
- Sexually dimorphic renal expression of mouse Klotho is directed by a kidney-specific distal enhancer responsive to HNF1b.Communications biology · 2024Article
- Nucleic acid and protein methylation modification in renal diseases.Acta pharmacologica Sinica · 2024Review
- Epigenetic roles in clonal hematopoiesis and aging kidney-related chronic kidney disease.Frontiers in cell and developmental biology · 2023Review
- Dihydroartemisinin suppresses renal fibrosis in mice by inhibiting DNA-methyltransferase 1 and increasing Klotho.Acta pharmacologica Sinica · 2022Article
- Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease.Scientific reports · 2022Article
- The relationship between polycyclic aromatic hydrocarbons exposure and serum klotho among adult population.BMC geriatrics · 2022Article
- The progress and prospect of natural components in rhubarb (Frontiers in pharmacology · 2022Review
- CCL5 Suppresses Klotho ExpressionFrontiers in physiology · 2022Article
- Age estimation using methylation-sensitive high-resolution melting (MS-HRM) in both healthy felines and those with chronic kidney disease.Scientific reports · 2021Article
- Epigenetic modifications of Klotho expression in kidney diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Acute Kidney Injury (AKI) before and after Kidney Transplantation: Causes, Medical Approach, and Implications for the Long-Term Outcomes.Journal of clinical medicine · 2021Review
- Epigenetics in kidney diseases.Advances in clinical chemistry · 2021Review
- Article
- Epigenetic regulation in AKI and kidney repair: mechanisms and therapeutic implications.Nature reviews. Nephrology · 2019Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Klotho (KL) expression is down-regulated in the renal tissues of chronic kidney disease (CKD) animal models and patients with end-stage renal disease. The putative role of KL promoter hypermethylation in the progression of CKD remains unclear. The present study aimed to determine renal and peripheral blood mononuclear cells (PBMC) levels of KL promoter methylation and analyze their relationship with clinical and histological severity in patients with CKD. Using bisulfite pyrosequencing, renal and PBMC levels of KL promoter methylation were quantified in 47 patients with CKD. 47 nephrectomy specimens of patients with renal cell carcinoma and 48 PBMC specimens of healthy volunteers were used as renal tissue and PBMC controls, respectively. Renal expression of KL protein was assayed by immunohistochemistry staining. Receiver operating characteristic (ROC) curve was used to identify the optimal cut-off value of PBMC KL promoter methylation level for renal KL promoter hypermethylation. Higher levels of KL promoter methylation were observed in renal tissue and PBMC in patients with CKD compared with controls (8.79±3.24 vs. 5.17±1.11%, P<0.001; 7.20±2.79 vs. 3.27±0.79%, P<0.001). In these patients, renal KL methylation level correlated inversely with renal KL immunostaining intensity (ρ=-0.794, P<0.001). Estimated glomerular filtration rate correlated inversely with renal and PBMC levels of KL promoter methylation (r=-0.829, P<0.001; r=-0.645, P<0.001), while tubulointerstistial fibrosis score correlated positively (ρ=0.826, P<0.001; ρ=0.755, P<0.001). PBMC KL promoter methylation level correlated positively with renal KL promoter methylation level in patients with CKD (r=0.787, P<0.001). In ROC curve, the area under curve was 0.964 (P<0.001) and the optimal cut-off value was 5.83% with a sensitivity of 93.8% and specificity of 86.7% to predict renal KL promoter hypermethylation. The degree of KL promoter methylation is associated with clinical and histological severity of CKD. PBMC KL promoter methylation level may act as a potential biomarker of renal KL promoter hypermethylation.
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