{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:56:02Z","timestamp":1789678562104,"version":"4.0.1"},"reference-count":38,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007338","name":"All India Institute of Medical Sciences","doi-asserted-by":"publisher","award":["A-1063"],"award-info":[{"award-number":["A-1063"]}],"id":[{"id":"10.13039\/501100007338","id-type":"DOI","asserted-by":"publisher"}]},{"award":["A-1063"],"award-info":[{"award-number":["A-1063"]}],"id":[{"id":"https:\/\/ror.org\/02dwcqs71","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Posterior urethral valves (PUV) cause congenital urinary tract obstruction and often lead to chronic kidney disease (CKD) despite treatment; however, DNA methylation remains underexplored in PUV. This cross-sectional study aimed to compare peripheral-blood global DNA methylation, measured as 5-methylcytosine content (5-mC%), between boys with PUV and age-matched male controls, and to assess its association with kidney function, CKD stage, and kidney scarring. The study included 45 boys with PUV and 45 age-matched boys as controls. Peripheral-blood global 5-mC% was quantified using an ELISA-based assay. Glomerular filtration rate and kidney scarring were assessed by nuclear scintigraphy, and PUV patients were categorized according to CKD stage and scarring status. Statistical comparisons were performed using the Kruskal\u2013Wallis test followed by Dunn\u2019s test, with exploratory trend analysis used to evaluate the association between global 5-mC% and CKD severity. Global 5-mC content was significantly higher in PUV patients than in controls (median 5-mC%: 0.4336 vs. 0.3732, p &lt; 0.001). Within the PUV cohort, global 5-mC% increased with CKD severity (p &lt; 0.05) and showed a logarithmic association with CKD stage (R2 = 0.8012). Patients with kidney scarring also had significantly higher global 5-mC% than controls (p &lt; 0.001), although differences across individual CKD stages and scarring subgroups were not statistically significant. These findings suggest altered systemic global 5-mC content in boys with PUV and support larger, longitudinal studies incorporating locus-specific methylation profiling.<\/jats:p>","DOI":"10.3390\/ijms27135649","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5649","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Global DNA Methylation in Children with Posterior Urethral Valves: Association with Kidney Function and Kidney Scarring"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0447-2350","authenticated-orcid":false,"given":"Sachit","family":"Anand","sequence":"first","affiliation":[{"name":"Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7246-9586","authenticated-orcid":false,"given":"Anjali","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0772-105X","authenticated-orcid":false,"given":"Ajay","family":"Verma","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himalaya","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitendra","family":"Meena","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3280-4778","authenticated-orcid":false,"given":"Chittaranjan","family":"Behera","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-2867","authenticated-orcid":false,"given":"Kalpana","family":"Luthra","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1007\/s00467-023-05899-w","article-title":"Congenital anomalies of the kidney and urinary tract: Defining risk factors of disease progression and determinants of outcomes","volume":"38","author":"Walawender","year":"2023","journal-title":"Pediatr. Nephrol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Pellegrino, C., Capitanucci, M.L., Forlini, V., Zaccara, A., Lena, F., Sollini, M.L., Castelli, E., and Mosiello, G. (2022). Posterior urethral valves: Role of prenatal diagnosis and long-term management of bladder function; a single center point of view and review of literature. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.1057092"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mizdrak, M., Kumri\u0107, M., Kurir, T.T., and Bo\u017ei\u0107, J. (2022). Emerging Biomarkers for Early Detection of Chronic Kidney Disease. J. Pers. Med., 12.","DOI":"10.3390\/jpm12040548"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"116922","DOI":"10.1016\/j.biopha.2024.116922","article-title":"A systematic review of epigenetic interplay in kidney diseases: Crosstalk between long noncoding RNAs and methylation, acetylation of chromatin and histone","volume":"176","author":"Tan","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Rysz, J., Franczyk, B., Rysz-G\u00f3rzy\u0144ska, M., and Gluba-Brz\u00f3zka, A. (2022). Are Alterations in DNA Methylation Related to CKD Development?. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137108"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"122256","DOI":"10.1016\/j.lfs.2023.122256","article-title":"Targeting DNA methylation in diabetic kidney disease: A new perspective","volume":"335","author":"Akhouri","year":"2023","journal-title":"Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hsueh, Y.-M., Chen, W.-J., Lee, H.-L., Huang, Y.-L., Shiue, H.-S., Hsu, S.-L., Chen, H.-H., and Lin, Y.-C. (2023). Global DNA methylation and the association between metal exposure and chronic kidney disease. Front. Public Health, 11.","DOI":"10.3389\/fpubh.2023.1104692"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/1744-9987.12238","article-title":"DNA methylation: Hemodialysis versus hemodiafiltration","volume":"19","author":"Ghigolea","year":"2015","journal-title":"Ther. Apher. Dial."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/npp.2012.112","article-title":"DNA methylation and its basic function","volume":"38","author":"Moore","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nrg3230","article-title":"Functions of DNA methylation: Islands, start sites, gene bodies and beyond","volume":"13","author":"Jones","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1101\/gad.947102","article-title":"DNA methylation patterns and epigenetic memory","volume":"16","author":"Bird","year":"2002","journal-title":"Genes. Dev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrg3142","article-title":"Epigenetics and the environment: Emerging patterns and implications","volume":"13","author":"Feil","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.cell.2013.12.019","article-title":"Reversing DNA methylation: Mechanisms, genomics, and biological functions","volume":"156","author":"Wu","year":"2014","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7891","DOI":"10.1038\/s41467-022-34963-6","article-title":"Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease","volume":"13","author":"Smyth","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejim.2023.07.045","article-title":"Elevated levels of IL-6 in IgA nephropathy patients are induced by an epigenetically driven mechanism modulated by viral and bacterial RNA","volume":"118","author":"Sallustio","year":"2023","journal-title":"Eur. J. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bowden, S.A., Stockwell, P.A., Rodger, E.J., Parry, M.F., Eccles, M.R., Stayner, C., and Chatterjee, A. (2020). Extensive Inter-Cyst DNA Methylation Variation in Autosomal Dominant Polycystic Kidney Disease Revealed by Genome Scale Sequencing. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00348"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.kint.2018.01.036","article-title":"Cytosine methylation predicts renal function decline in American Indians","volume":"93","author":"Qiu","year":"2018","journal-title":"Kidney Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"366","DOI":"10.4161\/epi.27161","article-title":"DNA hypermethylation and DNA hypomethylation is present at different loci in chronic kidney disease","volume":"9","author":"Smyth","year":"2014","journal-title":"Epigenetics"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1016\/S0140-6736(03)13372-7","article-title":"Folate treatment and unbalanced methylation and changes of allelic expression induced by hyperhomocysteinaemia in patients with uraemia","volume":"361","author":"Ingrosso","year":"2003","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.numecd.2017.06.011","article-title":"Cholesterol lowering treatment restores blood global DNA methylation in chronic kidney disease (CKD) patients","volume":"27","author":"Zinellu","year":"2017","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"216.e1","DOI":"10.1016\/j.jpurol.2015.04.022","article-title":"Posterior urethral valves: Metabolic consequences in a cohort of patients","volume":"11","author":"Sarhan","year":"2015","journal-title":"J. Pediatr. Urol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/1743-7075-9-36","article-title":"Exploring metabolic dysfunction in chronic kidney disease","volume":"9","author":"Slee","year":"2012","journal-title":"Nutr. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/s41581-021-00423-5","article-title":"Lipoproteins and fatty acids in chronic kidney disease: Molecular and metabolic alterations","volume":"17","author":"Noels","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41392-023-01379-7","article-title":"Kidney fibrosis: From mechanisms to therapeutic medicines","volume":"8","author":"Huang","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.kint.2020.10.012","article-title":"The case for early identification and intervention of chronic kidney disease: Conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference","volume":"99","author":"Shlipak","year":"2021","journal-title":"Kidney Int."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.euf.2024.05.024","article-title":"Diagnostic Test Accuracy of Urinary DNA Methylation-based Biomarkers for the Detection of Primary and Recurrent Bladder Cancer: A Systematic Review and Meta-analysis","volume":"10","author":"Carvalho","year":"2024","journal-title":"Eur. Urol. Focus."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/s41467-017-01297-7","article-title":"Epigenome-wide association studies identify DNA methylation associated with kidney function","volume":"8","author":"Chu","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s13073-021-00877-z","article-title":"Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci","volume":"13","author":"Breeze","year":"2021","journal-title":"Genome Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0022-5347(05)65453-5","article-title":"The valve bladder syndrome: Pathophysiology and treatment with nocturnal bladder emptying","volume":"167","author":"Koff","year":"2002","journal-title":"J. Urol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Hennus, P.M.L., van der Heijden, G.J.M.G., Bosch, J.L.H.R., de Jong, T.P.V.M., and de Kort, L.M.O. (2012). A Systematic Review on Renal and Bladder Dysfunction after Endoscopic Treatment of Infravesical Obstruction in Boys. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044663"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"480","DOI":"10.4103\/0970-1591.74434","article-title":"Etiopathogenesis and management of bladder dysfunction in patients with posterior urethral valves","volume":"26","author":"Thomas","year":"2010","journal-title":"Indian J. Urol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.trsl.2016.08.002","article-title":"Gut microbiome interactions with drug metabolism, efficacy, and toxicity","volume":"179","author":"Wilson","year":"2017","journal-title":"Transl. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1038\/s41392-023-01528-y","article-title":"Methylation across the central dogma in health and diseases: New therapeutic strategies","volume":"8","author":"Liu","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/jimd.12009","article-title":"Vitamin B12, folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation","volume":"42","author":"Froese","year":"2019","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13148-024-01642-w","article-title":"Kidney-specific methylation patterns correlate with kidney function and are lost upon kidney disease progression","volume":"16","author":"Sagy","year":"2024","journal-title":"Clin. Epigenet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41598-021-04321-5","article-title":"Longitudinal genome-wide DNA methylation changes in response to kidney failure replacement therapy","volume":"12","author":"Witasp","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_37","unstructured":"Bingham, G., Leslie, S.W., and Rentea, R.M. (2025). Posterior Urethral Valves, StatPearls Publishing."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2024). KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int., 105, S117\u2013S314.","DOI":"10.1016\/j.kint.2023.10.018"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5649\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:41:57Z","timestamp":1782272517000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/5649"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,23]]},"references-count":38,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27135649"],"URL":"https:\/\/doi.org\/10.3390\/ijms27135649","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,23]]}}}