{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:54:52Z","timestamp":1776682492662,"version":"3.51.2"},"reference-count":21,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Cell-free DNA (cfDNA) is released into the circulation during inflammation-driven cellular injury and regulated cell death. Elevated cfDNA concentrations have been reported in several clinical settings, including chronic kidney disease, hemodialysis, and peritoneal dialysis (PD). We previously demonstrated that PD-related peritonitis induces an increase in circulating cfDNA; however, the mechanisms underlying cfDNA generation remained unclear. This study aimed (i) to confirm peritoneal cfDNA variation following peritonitis in PD patients, and (ii) to elucidate the apoptotic pathways responsible for cfDNA release. Methods: Fifty-four PD patients were enrolled and stratified into the following groups: Group A\u2014no history of peritonitis (n = 25); Group B\u2014remote peritonitis &gt; 3 months prior (n = 21); Group C\u2014recent peritonitis &lt; 3 months prior (n = 8). cfDNA was quantified by qPCR. Apoptosis was assessed qualitatively by DNA laddering and quantitatively using ELISA assays for Caspase-3, Caspase-8 and Caspase-9. Results: cfDNA levels were significantly higher in patients with recent peritonitis compared to both other groups (p &lt; 0.01). DNA laddering showed enhanced nucleosomal fragmentation, consistent with apoptosis. Caspase-3 concentrations were markedly increased in recent peritonitis (&lt;3 months) and significantly correlated with cfDNA levels (\u03c1 = 0.511, p &lt; 0.01). Both Caspase-8 and Caspase-9 correlated with Caspase-3 (\u03c1 = 0.57 and \u03c1 = 0.47, respectively), indicating engagement of both extrinsic and intrinsic apoptotic pathways. Conclusions: In conclusion, peritoneal cfDNA in PD patients with peritonitis originates primarily from apoptosis and reflects dual-pathway caspase activation. cfDNA and Caspase-3 progressively decline with longer time elapsed from peritonitis, supporting their potential use as biomarkers for inflammatory activity and membrane recovery.<\/jats:p>","DOI":"10.3390\/genes17040488","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:37:42Z","timestamp":1776677862000},"page":"488","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual-Caspase-Mediated Apoptosis Underlies Peritoneal Cell-Free DNA Release After PD-Related Peritonitis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7934-9800","authenticated-orcid":false,"given":"Grazia Maria","family":"Virz\u00ec","sequence":"first","affiliation":[{"name":"IRRIV\u2014International Renal Research Institute Vicenza-Foundation, 36100 Vicenza, Italy"},{"name":"Department of Nephrology, Dialysis and Transplant, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Milan Manani","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplant, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3283-6297","authenticated-orcid":false,"given":"Matteo","family":"Marcello","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplant, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Porrovecchio","sequence":"additional","affiliation":[{"name":"IRRIV\u2014International Renal Research Institute Vicenza-Foundation, 36100 Vicenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6697-4065","authenticated-orcid":false,"given":"Claudio","family":"Ronco","sequence":"additional","affiliation":[{"name":"IRRIV\u2014International Renal Research Institute Vicenza-Foundation, 36100 Vicenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monica","family":"Zanella","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Dialysis and Transplant, San Bortolo Hospital, 36100 Vicenza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1053\/j.ajkd.2014.02.025","article-title":"Peritoneal Dialysis-Related Peritonitis: Towards Improving Evidence, Practices, and Outcomes","volume":"64","author":"Cho","year":"2014","journal-title":"Am. 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