{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:10:10Z","timestamp":1779340210617,"version":"3.51.4"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate the effects of combining hemoperfusion (HP) with high-flux hemodialysis (HFD) on T lymphocyte subsets, mitochondrial health, and clinical outcomes in patients undergoing maintenance hemodialysis (MHD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this single-center, prospective, self-controlled trial, 20 MHD patients received their regular HFD treatment, with the addition of a single HP session every 2\u202fweeks for 12 sessions. Levels of protein-bound uremic toxins (PBUTs: indoxyl sulphate [IS] and p-cresyl sulphate [PCS]), T lymphocyte subsets (CD3+, CD4+, CD8+), mitochondrial membrane potential (MMP) in T cells, and patient-reported outcomes (SF-36, PSQI, pruritus scale) were assessed before and after the 12 sessions intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following a single HP\u202f+\u202fHFD session, IS and PCS levels decreased significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001). However, their pre-perfusion levels at end were not significantly different from baseline. After 12 sessions, increases were observed in the levels of CD3+, CD4+, CD8\u202f+\u202fcells, the CD4+\/CD8\u202f+\u202fratio, and the percentages of CD3\u202f+\u202fMMP, CD4\u202f+\u202fMMP, and CD8\u202f+\u202fMMP (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.05). Patients also demonstrated significant improvements in sleep quality (PSQI), uremic pruritus, and overall quality of life (SF-36) (all\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.01). Additionally, serum phosphorus and parathyroid hormone levels were significantly reduced after the treatment period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>After 12 sessions of combined hemoperfusion and high-flux dialysis, we observed significant increases in T lymphocyte subsets (CD3+, CD4+, CD8+, CD4+\/CD8\u202f+\u202fratio) and the percentage of T cells with preserved mitochondrial membrane potential. Patients also reported improved sleep quality, reduced pruritus, and better quality of life. However, pre-dialysis levels of protein-bound uremic toxins (indoxyl sulphate and p-cresyl sulphate) of last session were not significantly different from baseline, despite effective clearance immediately after each combined session. Therefore, the observed improvements in immune-related parameters cannot be mechanistically attributed to a sustained reduction in these toxins. Alternative explanations\u2014such as intermittent attenuation of peak toxin concentrations, clearance of unmeasured solutes, or non-specific effects\u2014remain possible. Given the single-arm, observational design, these findings are hypothesis-generating and require confirmation in randomized controlled trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1765737","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:39:10Z","timestamp":1779338350000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Improving immune function and mitochondrial health in patients undergoing hemodialysis: benefits of combining high-flux dialysis with hemoperfusion"],"prefix":"10.3389","volume":"13","author":[{"given":"Qi","family":"Zhong","sequence":"first","affiliation":[{"name":"Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiudi","family":"Tu","sequence":"additional","affiliation":[{"name":"Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baoqiao","family":"Wu","sequence":"additional","affiliation":[{"name":"Nephrology Center, The Fourth Affiliated Hospital Zhejiang University School of Medicine","place":["Yiwu, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuemin","family":"Liu","sequence":"additional","affiliation":[{"name":"Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiwen","family":"Li","sequence":"additional","affiliation":[{"name":"Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Lin","sequence":"additional","affiliation":[{"name":"Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Ren","sequence":"additional","affiliation":[{"name":"Urology & Nephrology Center, Department of Nephrology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College","place":["Hangzhou, Zhejiang, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1001\/jamainternmed.2022.6817","article-title":"Prevalence of chronic kidney disease in China: results from the sixth China chronic disease and risk factor surveillance","volume":"183","author":"Wang","year":"2023","journal-title":"JAMA Intern Med"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1053\/j.ajkd.2020.11.021","article-title":"Estimation of prevalence of kidney disease treated with Dialysis in China: a study of insurance claims data","volume":"77","author":"Yang","year":"2021","journal-title":"Am J Kidney Diseases"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"l5873","DOI":"10.1136\/bmj.l5873","article-title":"Status of care for end stage kidney disease in countries and regions worldwide: international cross sectional survey","volume":"367","author":"Bello","year":"2019","journal-title":"BMJ"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1093\/ckj\/sfaa048","article-title":"The ERA-EDTA registry annual report 2017: a summary","volume":"13","author":"Kramer","year":"2020","journal-title":"Clin Kidney J"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1046\/j.1523-1755.2003.00924.x","article-title":"Review on uremic toxins: classification, concentration, and interindividual variability","volume":"63","author":"Vanholder","year":"2003","journal-title":"Kidney 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study","volume":"15","author":"Panthi","year":"2023","journal-title":"Cureus"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1053\/j.ajkd.2004.08.009","article-title":"Magnitude and impact of abnormal mineral metabolism in hemodialysis patients in the Dialysis outcomes and practice patterns study (DOPPS)","volume":"44","author":"Young","year":"2004","journal-title":"Am J Kidney Dis"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1938","DOI":"10.1093\/ndt\/gfq304","article-title":"Calcium, phosphorus, PTH and death rates in a large sample of dialysis patients from Latin America. The CORES study","volume":"26","author":"Naves-D\u00edaz","year":"2011","journal-title":"Nephrol Dial Transplant"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1093\/ndt\/gfy093","article-title":"Serum phosphate optimal timing and range associated with patients survival in haemodialysis: the COSMOS study","volume":"34","author":"Fern\u00e1ndez-Mart\u00edn","year":"2019","journal-title":"Nephrol Dial Transplant"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1056\/NEJMoa0706130","article-title":"Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis","volume":"359","author":"Guti\u00e9rrez","year":"2008","journal-title":"N Engl J Med"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1053\/j.ajkd.2008.03.020","article-title":"Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis outcomes and practice patterns study (DOPPS)","volume":"52","author":"Tentori","year":"2008","journal-title":"Am J Kidney Dis"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1765737\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:39:26Z","timestamp":1779338366000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1765737\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,21]]},"references-count":35,"alternative-id":["10.3389\/fmed.2026.1765737"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1765737","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,21]]},"article-number":"1765737"}}