{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:31:09Z","timestamp":1786113069581,"version":"build-2736575974"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Crearene AG","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients receiving hemodialysis are at risk of creatine deficiency due to impaired endogenous synthesis and losses during dialysis. Creatine deficiency is associated with lower health-related quality of life and higher mortality. We investigated the feasibility, tolerability and safety of intradialytic creatine supplementation during hemodialysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this double-blind, randomized, placebo-controlled pilot study (ClinicalTrials.gov ID: NCT05148208), 16 hemodialysis patients were included into four sequentially initiated groups, with each group receiving a fixed creatine concentration in the dialysate (0.5 mmol\/L, 1.0 mmol\/L, 1.5 mmol\/L and 2.0 mmol\/L, respectively), with block randomization in a 3:1 ratio (creatine:placebo) per group. Dropouts were replaced. Intra-dialytic creatine was administered during a 6-week period. Primary outcomes were changes in pre-dialytic intra-erythrocytic and plasma creatine concentrations, which were analyzed with linear mixed models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>16 hemodialysis patients (aged 27\u201378 years, 9 female) completed the study. Creatine supplementation was generally well tolerated. One patient receiving 1.5 mmol\/L creatine dropped out due to a potential side effect. No serious adverse events occurred. The median (minimum-maximum) baseline pre-dialytic intra-erythrocytic and plasma creatine concentrations were 963 (407\u20131822) and 35 (13\u2013287) \u00b5mol\/L, respectively. At 6 weeks, the changes in pre-dialytic intra-erythrocytic creatine concentration compared to placebo (95% CI) were +399 (\u2212269, 1066),\u2009+\u2009685 (+17,\u2009+\u20091352),\u2009+\u20091146 (+431,\u2009+\u20091766) and +1098 (+431,\u2009+\u20091766) \u00b5mol\/L for the increasing dosage treatment groups respectively (overall treatment effect p\u2009&lt;\u20090.001). The changes in pre-dialytic plasma creatine concentration compared to placebo were \u221216 (\u2212301,\u2009+\u2009270),\u2009+\u200921 (\u2212264,\u2009+\u2009307),\u2009+\u2009119 (\u2212264,\u2009+\u2009307) and +163 (\u2212122,\u2009+\u2009449) \u00b5mol\/L for the increasing dosage treatment groups respectively (overall treatment effect p\u2009=\u20090.002).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Intra-dialytic creatine supplementation is a feasible, safe, well-tolerated method to increase circulating creatine concentrations in patients treated with hemodialysis. These findings support the rationale for a larger randomized controlled trial to investigate its potential to improve health-related quality of life and reduce mortality risk in this population.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      ClinicalTrials.gov ID NCT05148208, date of first registration 08\/12\/2021\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0354883","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:28:09Z","timestamp":1785950889000},"page":"e0354883","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Feasibility, safety and tolerability of intradialytic creatine supplementation in hemodialysis: A double-blind, randomized, placebo-controlled pilot study"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8036-520X","authenticated-orcid":true,"given":"Caecilia S. 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