{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:03:23Z","timestamp":1789653803751,"version":"4.0.0"},"reference-count":65,"publisher":"Wiley","issue":"17","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\/"},{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"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":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Acute kidney injury (AKI) affects approximately 30%\u201360% of intensive care unit (ICU) admissions, but early detection remains difficult because creatinine\u2010 and urine\u2010output\u2010based KDIGO criteria are delayed and confounded in critical illness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To summarize the biomarker landscape for ICU\u2010associated AKI, focusing on kidney\u2010targeted injury\/stress proteins and circulating cell\u2010free DNA (cfDNA), including mitochondrial DNA (mtDNA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed\/MEDLINE and Embase were searched from inception to December 31, 2025, using terms related to AKI, critical illness, NGAL, KIM\u20101, IL\u201018, L\u2010FABP, [TIMP\u20102]\u00b7[IGFBP7], cfDNA, mtDNA, and damage\u2010associated molecular patterns. Adult ICU studies reporting diagnostic performance, risk stratification, or clinically relevant outcomes were prioritized, especially in sepsis, cardiac surgery, shock, and trauma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>NGAL, KIM\u20101, IL\u201018, L\u2010FABP, and [TIMP\u20102]\u00b7[IGFBP7] often rise before creatinine or urine\u2010output changes, providing early kidney\u2010proximal signals of tubular injury or stress. cfDNA\/mtDNA instead reflects systemic cell death, mitochondrial damage, and innate immune activation, capturing multi\u2010organ injury and adding prognostic information beyond clinical scores and creatinine. Across ICU phenotypes, combining clinical risk, an early kidney\u2010targeted marker, and cfDNA\/mtDNA may improve identification of patients at risk for severe AKI, renal replacement therapy, and death.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Multimarker strategies may widen the diagnostic window and sharpen prognostication in ICU\u2010associated AKI. Routine implementation will require standardized pre\u2010analytical handling, assay harmonization, biomarker\u2010guided pragmatic trials, and trajectory\u2010based decision tools that demonstrate clinical benefit.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcla.70311","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T07:05:31Z","timestamp":1785913531000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Landscape of Biomarkers in\n                    <scp>ICU<\/scp>\n                    \u2010Associated\n                    <scp>AKI<\/scp>\n                    : From Protein Markers to Cell\u2010Free Nucleic Acids"],"prefix":"10.1002","volume":"40","author":[{"given":"Qi","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Emergency Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9844-8182","authenticated-orcid":false,"given":"Feng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Nephrology Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Nephrology Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoli","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Emergency Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8319-5369","authenticated-orcid":false,"given":"Zhenhua","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Nephrology Central Hospital Affiliated to Shenyang Medical College  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-018-0052-0"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2005.01.069"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/tsaco-2024-001381"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2008.11.034"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016010105"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10916-016-0528-z"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2024.06.021"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13613-024-01360-9"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e318228234b"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.1999.00515.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40620-018-0539-6"},{"issue":"1","key":"e_1_2_11_13_1","first-page":"21","article-title":"The Definition and Detection of Acute Kidney Injury","volume":"3","author":"Pickering J. 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