{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T06:19:02Z","timestamp":1787811542690,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/19631\u20107"],"award-info":[{"award-number":["2019\/19631\u20107"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021529","name":"Prince of Wales Hospital Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021529","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012624","name":"Jerry M. Lewis, M.D. Mental Health Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012624","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018868","name":"Sphingotec GmbH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Reduced kidney functional reserve, KFR, predicts poor outcomes in kidney diseases. We compared plasma proenkephalin\u2010A, plasma cystatin C, and creatinine clearance for kidney functional reserve measurement. KFR was measured preoperatively in 40 patients undergoing cardiac surgery and 22 healthy participants, including 14 kidney donors. Plasma proenkephalin\u2010A, cystatin C, and creatinine levels were compared before and after a protein meal for KFR calculation. Baseline creatinine clearance correlated poorly with baseline estimated glomerular filtration rate measured by any method. Cystatin C and proenkephalin\u2010A nadir after protein occurred earlier. The proenkephalin\u2010A\u2010based KFR had a greater dynamic range than cystatin C\u2010 and creatinine clearance\u2010based KFR (median [IQR] fractional KFR: proenkephalin\u2010A 44.2% [35.5; 58.0]; cystatin C 10.5% [4.4; 16.2]; creatinine clearance 30.0% [8.4; 68.9],\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Measurements were more homogeneous with cystatin C\u2010 and proenkephalin\u2010A\u2010estimated glomerular filtration rate than creatinine clearance (higher intraclass correlation: 0.98 for cystatin C; 0.86 for proenkephalin\u2010A, and 0.63 for creatinine clearance). The median [IQR] absolute proenkephalin\u2010A\u2010 and cystatin C\u2010based KFR were higher in healthy participants (proenkephalin\u2010A\u2010KFR: 33.8 [26.6; 59.0], cystatin C\u2010KFR: 11.6 [6.6; 15.1] mL\/min\/1.73m\n                    <jats:sup>2<\/jats:sup>\n                    ) than cardiac surgery patients (proenkephalin\u2010A\u2010reserve: 28.5 [19.9; 40.6], cystatin C\u2010reserve: 5.0 [0.3; 8.7] mL\/min\/1.73m\n                    <jats:sup>2<\/jats:sup>\n                    ,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Creatinine clearance\u2010KFR did not differ between groups and mostly reflected tubular secretion of creatinine than change in glomerular filtration rate. In conclusion, proenkephalin\u2010A provided a brief, homogeneous measure of KFR with wide dynamic range, encouraging wider use of this kidney stress test.\n                  <\/jats:p>","DOI":"10.14814\/phy2.71083","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:52:27Z","timestamp":1787806347000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma proenkephalin\u2010a facilitates measurement of human kidney functional reserve: From healthy kidney donors to polymorbid patients"],"prefix":"10.14814","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0562-0893","authenticated-orcid":false,"given":"Camila Eleuterio","family":"Rodrigues","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Faculty of Medicine and Health University of New South Wales  Sydney New South Wales Australia"},{"name":"Department of Nephrology Prince of Wales Hospital  Sydney New South Wales Australia"},{"name":"Hospital das Cl\u00ednicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo  S\u00e3o Paulo SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy Y. M.","family":"Au","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Faculty of Medicine and Health University of New South Wales  Sydney New South Wales Australia"},{"name":"Department of Nephrology Prince of Wales Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Rebello","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Faculty of Medicine and Health University of New South Wales  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Maawad","sequence":"additional","affiliation":[{"name":"Department of Nephrology Prince of Wales Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Uhle","sequence":"additional","affiliation":[{"name":"SphingoTec GmbH  Hennigsdorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Erlich","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Faculty of Medicine and Health University of New South Wales  Sydney New South Wales Australia"},{"name":"Department of Nephrology Prince of Wales Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4782-8695","authenticated-orcid":false,"given":"Zoltan H.","family":"Endre","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Faculty of Medicine and Health University of New South Wales  Sydney New South Wales Australia"},{"name":"Department of Nephrology Prince of Wales Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1111\/j.1440-1797.2010.01291.x","article-title":"Functional renal reserve capacity in different stages of chronic kidney disease","volume":"15","author":"Barai S.","year":"2010","journal-title":"Nephrology (Carlton)"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1016\/j.ekir.2023.08.006","article-title":"Assessing GFR with Proenkephalin","volume":"8","author":"Beunders R.","year":"2023","journal-title":"Kidney International Reports"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1097\/SHK.0000000000001510","article-title":"Proenkephalin compared to conventional methods to assess kidney function in critically ill sepsis patients","volume":"54","author":"Beunders R.","year":"2020","journal-title":"Shock"},{"key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/S0272-6386(88)80081-7","article-title":"Renal functional reserve in live related kidney donors","volume":"11","author":"Cassidy M. 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