{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T21:49:51Z","timestamp":1793396991638,"version":"4.5.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,9,3]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Kidney disease is common in heart failure with preserved ejection fraction (HFpEF). However, the biologic correlates and prognostic significance of kidney injury (KI), in HFpEF, beyond the estimated glomerular filtration rate (eGFR), are unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Using baseline plasma samples from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, we measured the following KI biomarkers: cystatin\u2010C, fatty acid\u2010binding protein\u20103, Beta\u20102 microglobulin, neutrophil gelatinase\u2010associated lipocalin, and kidney\u2010injury molecule\u20101. Factor analysis was used to extract the common variability underlying these biomarkers. We assessed the relationship between the KI\u2010factor score and the risk of death or HF\u2010related hospital admission in models adjusted for the Meta\u2010Analysis Global Group in Chronic Heart Failure risk score and eGFR. We also assessed the relationship between the KI factor score and ~5000 plasma proteins, followed by pathway analysis. We validated our findings among HFpEF participants in the Penn Heart Failure Study. KI was associated with the risk of death or HF\u2010related hospital admission independent of the Meta\u2010Analysis Global Group in Chronic Heart Failure risk score and eGFR. Both the risk score and eGFR were no longer associated with death or HF\u2010related hospital admission after adjusting for the KI factor score. KI was predominantly associated with proteins and biologic pathways related to complement activation, inflammation, fibrosis, and cholesterol homeostasis. KI was associated with 140 proteins, which reproduced across cohorts. Findings regarding biologic associations and the prognostic significance of KI were also reproduced in the validation cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">KI is associated with adverse outcomes in HFpEF independent of baseline eGFR. Patients with HFpEF and KI exhibit a plasma proteomic signature indicative of complement activation, inflammation, fibrosis, and impaired cholesterol homeostasis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.033660","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T06:30:14Z","timestamp":1724913014000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["Proteomic Correlates and Prognostic Significance of Kidney Injury in Heart Failure With Preserved Ejection Fraction"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8390-1036","authenticated-orcid":false,"given":"Oday","family":"Salman","sequence":"first","affiliation":[{"name":"Hospital of the University of Pennsylvania","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7099-3712","authenticated-orcid":false,"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb Company","place":["Princeton, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4649-079X","authenticated-orcid":false,"given":"Jordana B.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Hospital of the University of Pennsylvania","place":["Philadelphia, USA"]},{"name":"University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7591-5684","authenticated-orcid":false,"given":"Marie Joe","family":"Dib","sequence":"additional","affiliation":[{"name":"Hospital of the University of Pennsylvania","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8161-9611","authenticated-orcid":false,"given":"Joe David","family":"Azzo","sequence":"additional","affiliation":[{"name":"Hospital of the University of Pennsylvania","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushrima","family":"Gan","sequence":"additional","affiliation":[{"name":"Hospital of the University of Pennsylvania","place":["Philadelphia, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2023-8177","authenticated-orcid":false,"given":"A. 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