{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:45:31Z","timestamp":1785869131874,"version":"3.56.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":683,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T00:00:00Z","timestamp":1701475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This retrospective cohort study aimed to be the first to evaluate the association between plasma protein-bound uremic toxins (PBUTs) concentrations, echocardiographic parameters of heart failure (HF), and incident HF events in patients with chronic kidney disease (CKD) not on dialysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Retrospective, single-centre, cohort study at the Ghent University Hospital, Belgium. Adults with CKD stages G1\u2013G5, not on dialysis, could be included. Exclusion criteria were ongoing pregnancy, age &amp;lt;18 years, active acute infection, active malignancy, history of transplantation, or a cardiovascular event within 3 months prior to inclusion. Free and total concentrations of five PBUTs were quantified at baseline: indoxyl sulfate (IxS), p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG), indole-3 acetic acid (IAA), and hippuric acid (HA). Patients were grouped into three echocardiographic categories: normal left ventricular ejection fraction (LVEF) and normal left ventricular end-diastolic pressure (LVEDP), normal LVEF and increased LVEDP, and reduced LVEF, based on available echocardiographic data in a time interval of \u00b16 months around the plasma sample collection. A total of 523 patients were included between January 2011 and January 2014. Echocardiographic data within the predefined timeframe were available for 210 patients (40% of patients). Levels of pCG and pCS were significantly higher in patients with reduced (&amp;lt;50%) versus normal LVEF (P &amp;lt; 0.05). After a median follow-up 5.5 years, 43 (8.4%) patients reached the composite endpoint of hospitalization or mortality due to HF. Free fractions of IxS, pCS, and pCG showed the strongest association with clinical outcome: free IxS: HR 1.71 (95% CI 1.11\u20132.63; P = 0.015), free pCS: HR 1.82 (95% CI 1.11\u20133.01; P = 0.019), and free pCG: HR 1.67 (95% CI 1.08\u20132.58; P = 0.020), and these results were independent of age, gender, body mass index, diabetes, and systolic blood pressure. In models that were also adjusted for serum creatinine, the free fractions of these PBUTs remained significant.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated free concentrations of IxS, pCG, and pCS were independently associated with an increased risk of HF events in non-dialysed CKD patients. Further research is necessary to confirm these findings and investigate the potential impact of PBUT-lowering interventions on HF events in this patient group.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14566","type":"journal-article","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T12:11:56Z","timestamp":1701519116000},"page":"466-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Predictive Value of Protein-Bound Uremic Toxins for Heart Failure in Patients with Chronic Kidney Disease"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3786-6222","authenticated-orcid":false,"given":"Bert","family":"Zwaenepoel","sequence":"first","affiliation":[{"name":"Department of Cardiology, Ghent University Hospital, Ghent University , Ghent ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine","family":"De Backer","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Ghent University Hospital, Ghent University , Ghent ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Griet","family":"Glorieux","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Ghent University Hospital, Ghent University , Ghent ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Verbeke","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Ghent University Hospital, Ghent University , Ghent ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,2]]},"reference":[{"key":"2026012113080233800_ehf214566-bib-0001","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.1136\/heartjnl-2016-310794","article-title":"Heart failure in patients with kidney disease","volume":"103","author":"Tuegel","year":"2017","journal-title":"Heart"},{"key":"2026012113080233800_ehf214566-bib-0002","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10090352","article-title":"Cardiotoxicity of uremic toxins: a driver of cardiorenal syndrome","volume":"10","author":"Lekawanvijit","year":"2018","journal-title":"Toxins (Basel)"},{"key":"2026012113080233800_ehf214566-bib-0003","doi-asserted-by":"publisher","DOI":"10.3390\/toxins10090352","article-title":"US renal data system 2016 annual data report: Epidemiology of kidney disease in the United States","volume":"10","author":"Saran","journal-title":"Am J Kidney Dis"},{"key":"2026012113080233800_ehf214566-bib-0004","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1681\/ASN.2006101159","article-title":"Reduced kidney function as a risk factor for incident heart failure: The atherosclerosis risk in communities (ARIC) study","volume":"18","author":"Kottgen","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"2026012113080233800_ehf214566-bib-0005","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.2215\/CJN.09990915","article-title":"Predictors and outcomes of health-related quality of life in adults with CKD","volume":"11","author":"Porter","year":"2016","journal-title":"Clin J Am Soc Nephrol"},{"key":"2026012113080233800_ehf214566-bib-0006","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1161\/CIRCULATIONAHA.120.050686","article-title":"Cardiovascular disease in chronic kidney disease: Pathophysiological insights and therapeutic options","volume":"143","author":"Jankowski","year":"2021","journal-title":"Circulation"},{"key":"2026012113080233800_ehf214566-bib-0007","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.686249","article-title":"Uremic toxins: An alarming danger concerning the cardiovascular system","volume":"12","author":"Falconi","year":"2021","journal-title":"Front Physiol"},{"key":"2026012113080233800_ehf214566-bib-0008","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 Int"},{"key":"2026012113080233800_ehf214566-bib-0009","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1093\/ndt\/15.1.50","article-title":"Intradialytic removal of protein-bound uraemic toxins: Role of solute characteristics and of dialyser membrane","volume":"15","author":"Lesaffer","year":"2000","journal-title":"Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - 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