{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:39:17Z","timestamp":1786977557965,"version":"build-2736575974"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Comprehensive Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Kidney dysfunction is prevalent but insufficiently understood in Fontan patients. We aimed to investigate Fontan\u2010Associated Renal Disease (FARD) through comprehensive phenotyping using biomarkers of renal function and injury, as well as ultrasound assessment of intrarenal hemodynamics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively collected data on serum creatinine and cystatin C levels, and 24\u2010h urine creatinine clearance and albumin excretion in 25 Fontan patients, comparing them to healthy age\u2010 and sex\u2010matched controls. Additionally, we measured intrarenal venous and arterial flow patterns using Doppler ultrasonography.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median age was 28 (Q1\u2013Q3: 19\u201335) years, with 48% female. Compared to controls, Fontan patients had similar creatinine\u2010based eGFR (eGFR\n                      <jats:sub>cr<\/jats:sub>\n                      ) (114 vs. 106\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.2), lower cystatin C\u2010based eGFR (eGFR\n                      <jats:sub>cys<\/jats:sub>\n                      ) (96 vs. 106\u2009mL\/min\/1.73\u2009m\n                      <jats:sup>2<\/jats:sup>\n                      ;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.045), and lower 24\u2010h urinary creatinine excretion (10.0 vs. 13.7\u2009mmol\/24\u2009h;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Additionally, patients had higher 24\u2010h urine albumin excretion (14 vs. 2\u2009mg\/24\u2010h;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In patients, both eGFR\n                      <jats:sub>cys<\/jats:sub>\n                      and urine albumin correlated with age (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u2009\u22120.56 and\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.44, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Twenty\u2010\u2010four out of 25 patients and all controls had continuous intrarenal venous flow patterns. Venous impedance and arterial renal resistance indices were higher in patients than controls (0.44 vs. 0.14 and 0.67 vs. 0.60, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      FARD involves a progressive decline in kidney function and glomerular injury. eGFR\n                      <jats:sub>cr<\/jats:sub>\n                      masks kidney dysfunction in Fontan patients due to reduced muscle mass. Fontan intrarenal hemodynamics demonstrate decreased venous and arterial compliance. Moreover, continuous intrarenal venous flow persists in Fontan patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cph4.70116","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T02:41:18Z","timestamp":1773196878000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Phenotyping of Fontan\u2010Associated Renal Physiology and Disease"],"prefix":"10.1002","volume":"16","author":[{"given":"Gaston","family":"van Hassel","sequence":"first","affiliation":[{"name":"University of Groningen, Center for Congenital Heart Diseases, Department of Paediatric Cardiology Beatrix Children's Hospital, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozine M.","family":"ter Maaten","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris E.","family":"Beldhuis","sequence":"additional","affiliation":[{"name":"Department of Cardiology University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eryn T.","family":"Liem","sequence":"additional","affiliation":[{"name":"University of Groningen, Center for Congenital Heart Diseases, Department of Paediatric Cardiology Beatrix Children's Hospital, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bastiaan","family":"Zwart","sequence":"additional","affiliation":[{"name":"Center for Congenital Heart Diseases, Department of Cardiology University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan J. L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"University of Groningen, Department of Internal Medicine, Division of Nephrology University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4385-5784","authenticated-orcid":false,"given":"Rolf M. F.","family":"Berger","sequence":"additional","affiliation":[{"name":"University of Groningen, Center for Congenital Heart Diseases, Department of Paediatric Cardiology Beatrix Children's Hospital, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost P.","family":"van Melle","sequence":"additional","affiliation":[{"name":"Center for Congenital Heart Diseases, Department of Cardiology University of Groningen, University Medical Center Groningen  Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2016-310108"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2014-305723"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2021.12.005"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2006.050"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13101687"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2021.08.003"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.26.3.240"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2015-307467"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12969"},{"issue":"12","key":"e_1_2_11_11_1","first-page":"1","article-title":"Deterioration in Renal Function in Patients With a Fontan Circulation and Association With Mortality","volume":"3","author":"Hassel G. v.","year":"2024","journal-title":"JACC: Advances"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2016.03.016"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2022.10.028"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00380-017-1063-7"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2012.04.015"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2201153"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardfail.2020.09.003"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm13101481"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.09.043"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1258\/0004563021901847"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0803.2012.00717.x"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2016-309729"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.826096"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.003887"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-20-0332"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom13071075"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2016.05.009"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.114.001536"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2017.05.005"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-025-04040-3"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.05.042"}],"container-title":["Comprehensive Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cph4.70116","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cph4.70116","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cph4.70116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T07:20:10Z","timestamp":1777015210000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cph4.70116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/cph4.70116"],"URL":"https:\/\/doi.org\/10.1002\/cph4.70116","archive":["Portico"],"relation":{},"ISSN":["2040-4603","2040-4603"],"issn-type":[{"value":"2040-4603","type":"print"},{"value":"2040-4603","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]},"assertion":[{"value":"2025-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70116"}}