{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:42:11Z","timestamp":1759365731613,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: The objectives of this review were as follows: to measure changes in renal biomarker levels before, immediately after, and 24 h post-marathon; to identify promising biomarkers for the diagnosis of acute kidney injury; and to describe the temporal patterns of biomarker dynamics in relation to the marathon. Materials and Methods: Studies of marathon runners reporting AKI-related biomarkers were included. Four databases (PubMed, EMBASE, Web of Science, and LILACS) were searched. Data on study design, participant characteristics, and biomarker values (pre-, post-, and 24 h post-race) were extracted, and a random effects meta-analysis was performed. Risk of bias was assessed with the National Heart, Lung, and Blood Institute pre\u2013post tool. Results: The study showed significant increases in most biomarkers immediately after the marathon compared to baseline values. The largest increases were observed in Tissue Inhibitor of Metalloproteinases-2* Insulin-like Growth Factor Binding Protein-7 (TIMP-2*IGFBP), copeptin, urinary Liver-type Fatty Acid Binding Protein (L-FABP), urinary Monocyte Chemoattractant Protein-1 (MCP-1), IGFBP-7, urinary Chitinase 3-like Protein 1 (YKL-40), and TIMP-2, suggesting that these biomarkers are promising candidates for future research. Several patterns of biomarker evolution were observed: some increased without decreasing even at 24 h after the marathon; others increased post-marathon and decreased at 24 h while remaining above baseline; some increased after the marathon and then fell below baseline at 24 h. Conclusions: Marathon running causes significant increases in kidney injury biomarkers, with different patterns of evolution.<\/jats:p>","DOI":"10.3390\/medicina61101775","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:37:21Z","timestamp":1759311441000},"page":"1775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Acute Kidney Injury Biomarkers in Marathon Runners: Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4218-8622","authenticated-orcid":false,"given":"Daniel-Corneliu","family":"Leucu\u021ba","sequence":"first","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loredana-Ioana","family":"Trif","sequence":"additional","affiliation":[{"name":"Department of Medical Informatics and Biostatistics, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8800-4935","authenticated-orcid":false,"given":"Oana","family":"Alm\u0103\u0219an","sequence":"additional","affiliation":[{"name":"Department of Prosthetic Dentistry and Dental Materials, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 32 Clinicilor Street, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5508-2598","authenticated-orcid":false,"given":"\u0218tefan Lucian","family":"Popa","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-271X","authenticated-orcid":false,"given":"Abdulrahman","family":"Ismaiel","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zuo, Y., Zou, L., Zhang, M., Smith, L., Yang, L., Loprinzi, P.D., and Ren, Z. (2019). The Temporal and Spatial Evolution of Marathons in China from 2010 to 2018. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16245046"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhu, H., Han, X., Miao, G., and Yan, Q. (2024). A Preliminary Exploration of the Regression Equation for Performance in Amateur Half-Marathon Runners: A Perspective Based on Respiratory Muscle Function. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1340513"},{"key":"ref_3","unstructured":"RunSignup (2025, August 20). Annual Industry Report 2024 (RaceTrends 2024). Available online: https:\/\/info.runsignup.com\/wp-content\/uploads\/sites\/3\/2025\/01\/24-Race-Trends-08-Online-compressed.pdf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1007\/s40279-015-0359-y","article-title":"Meta-Analyses of the Effects of Habitual Running on Indices of Health in Physically Inactive Adults","volume":"45","author":"Pillay","year":"2015","journal-title":"Sports Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s40798-025-00810-3","article-title":"Physiology and Pathophysiology of Marathon Running: A Narrative Review","volume":"11","author":"Braschler","year":"2025","journal-title":"Sports Med. Open"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s40279-021-01561-3","article-title":"Potential Long-Term Health Problems Associated with Ultra-Endurance Running: A Narrative Review","volume":"52","author":"Scheer","year":"2022","journal-title":"Sports Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1053\/j.ajkd.2017.01.045","article-title":"Kidney Injury and Repair Biomarkers in Marathon Runners","volume":"70","author":"Mansour","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.2215\/CJN.01400219","article-title":"The Role of Volume Regulation and Thermoregulation in AKI during Marathon Running","volume":"14","author":"Mansour","year":"2019","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_9","first-page":"75","article-title":"Acute Kidney Injury","volume":"36","author":"Goyal","year":"2023","journal-title":"Crit. Care Nurse"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"c179","DOI":"10.1159\/000339789","article-title":"KDIGO Clinical Practice Guidelines for Acute Kidney Injury","volume":"120","author":"Khwaja","year":"2012","journal-title":"Nephron Clin. Pr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000442365","article-title":"The Acute Kidney Injury to Chronic Kidney Disease Transition: A Potential Opportunity to Improve Care in Acute Kidney Injury","volume":"187","author":"Palant","year":"2016","journal-title":"Contrib. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e000093","DOI":"10.1136\/bmjsem-2015-000093","article-title":"Acute Kidney Injury Associated with Endurance Events\u2014Is It a Cause for Concern? A Systematic Review","volume":"3","author":"Hodgson","year":"2017","journal-title":"BMJ Open Sport Exerc. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1080\/0886022X.2020.1721300","article-title":"A Long Journey for Acute Kidney Injury Biomarkers","volume":"42","author":"Oh","year":"2020","journal-title":"Ren. Fail."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_15","unstructured":"Corporation for Digital Scholarship (2024, May 29). Open-Source Reference Management Software, Zotero, Available online: https:\/\/www.zotero.org\/."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Higgins, J.P.T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M.J., and Welch, V.A. (2019). Cochrane Handbook for Systematic Reviews of Interventions, Wiley-Blackwell. [2nd ed.].","DOI":"10.1002\/9781119536604"},{"key":"ref_17","unstructured":"National Heart, Lung, and Blood Institute (2025, August 20). Study Quality Assessment Tools, Available online: https:\/\/www.nhlbi.nih.gov\/health-topics\/study-quality-assessment-tools."},{"key":"ref_18","first-page":"40","article-title":"Meta: An R Package for Meta-Analysis","volume":"7","author":"Schwarzer","year":"2007","journal-title":"R. News"},{"key":"ref_19","unstructured":"R Core Team (2024). A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jsams.2022.10.012","article-title":"Marathon Running and Cell-Cycle Arrest Biomarkers of Acute Kidney Injury","volume":"26","author":"Leckie","year":"2023","journal-title":"J. Sci. Med. Sport"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/japplphysiol.00669.2021","article-title":"Xanthine Oxidoreductase Activity in Marathon Runners: Potential Implications for Marathon-Induced Acute Kidney Injury","volume":"133","author":"Kosaki","year":"2022","journal-title":"J. Appl. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Atkins, W.C., Butts, C.L., Kelly, M.R., Troyanos, C., Laursen, R.M., Duckett, A., Emerson, D.M., Rosa-Caldwell, M.E., and McDermott, B.P. (2022). Acute Kidney Injury Biomarkers and Hydration Outcomes at the Boston Marathon. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.813554"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Nescolarde, L., Roca, E., Bog\u00f3nez-Franco, P., Hern\u00e1ndez-Hermoso, J., Bayes-Genis, A., and Ara, J. (2020). Relationship Be-tween Bioimpedance Vector Displacement and Renal Function After a Marathon in Non-Elite Runners. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00352"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1111\/j.1440-1797.2010.01354.x","article-title":"Changes in Renal Markers and Acute Kidney Injury after Marathon Running","volume":"16","author":"Mccullough","year":"2011","journal-title":"Nephrology"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Bekos, C., Zimmermann, M., Unger, L., Janik, S., Hacker, P., Mitterbauer, A., Koller, M., Fritz, R., G\u00e4bler, C., and Kessler, M. (2016). Non-Professional Marathon Running: RAGE Axis and ST2 Family Changes in Relation to Open-Window Effect, Inflammation and Renal Function. Sci. Rep., 6.","DOI":"10.1038\/srep32315"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12947-015-0007-6","article-title":"Cardiac and Renal Function in a Large Cohort of Amateur Marathon Runners","volume":"13","author":"Hewing","year":"2015","journal-title":"Cardiovasc. Ultrasound"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"125","DOI":"10.2165\/00007256-198401020-00003","article-title":"Exercise and Renal Function","volume":"1","author":"Poortmans","year":"1984","journal-title":"Sports Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1249\/01.mss.0000218134.74238.6a","article-title":"Continuous Thermoregulatory Responses to Mass-Participation Distance Running in Heat","volume":"38","author":"Byrne","year":"2006","journal-title":"Med. Sci. Sports Exerc."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1152\/japplphysiol.00787.2019","article-title":"Both Hyperthermia and Dehy-dration during Physical Work in the Heat Contribute to the Risk of Acute Kidney Injury","volume":"128","author":"Chapman","year":"2020","journal-title":"J. Appl. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Schlader, Z.J., Hostler, D., Parker, M.D., Pryor, R.R., Lohr, J.W., Johnson, B.D., and Chapman, C.L. (2019). The Potential for Renal Injury Elicited by Physical Work in the Heat. Nutrients, 11.","DOI":"10.3390\/nu11092087"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.matbio.2015.03.005","article-title":"The Role of TIMPs in Regulation of Extracellular Matrix Proteolysis","volume":"44\u201346","author":"Arpino","year":"2015","journal-title":"Matrix Biol."},{"key":"ref_32","first-page":"F894","article-title":"Extracellular Matrix-Related Genes in Kidney after Ischemic Injury: Potential Role for TGF-\u03b2 in Repair","volume":"275","author":"Basile","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7602","DOI":"10.1002\/jcb.28035","article-title":"IGFBP7 Regulates Sepsis-Induced Acute Kidney Injury through ERK1\/2 Signaling","volume":"120","author":"Wang","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/cc12503","article-title":"Discovery and Validation of Cell Cycle Arrest Biomarkers in Human Acute Kidney Injury","volume":"17","author":"Kashani","year":"2013","journal-title":"Crit. Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.33176\/AACB-20-00001","article-title":"The Emerging Role of Copeptin","volume":"42","author":"Jalleh","year":"2021","journal-title":"Clin. Biochem. Rev."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cca.2006.05.038","article-title":"Urinary Fatty Acid Binding Protein in Renal Disease","volume":"374","author":"Sugaya","year":"2006","journal-title":"Clin. Chim. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/s11010-005-9047-9","article-title":"Urinary Liver-Type Fatty Acid Binding Protein as a Useful Biomarker in Chronic Kidney Disease","volume":"284","author":"Kamijo","year":"2006","journal-title":"Mol. Cell. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"107598","DOI":"10.1016\/j.intimp.2021.107598","article-title":"MCP-1: Function, Regulation, and Involvement in Disease","volume":"101","author":"Singh","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1081\/JDI-120015673","article-title":"Monocyte Chemoattractant Protein-1 Expression Correlates with Monocyte Infiltration in the Post-Ischemic Kidney","volume":"24","author":"Rice","year":"2002","journal-title":"Ren. Fail."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Stroo, I., Claessen, N., Teske, G.J., Butter, L.M., Florquin, S., and Leemans, J.C. (2015). Deficiency for the Chemokine Monocyte Chem-oattractant Protein-1 Aggravates Tubular Damage after Renal Ischemia\/Reperfusion Injury. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123203"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.canlet.2012.10.014","article-title":"Tumor Necrosis Factor","volume":"328","author":"Chu","year":"2013","journal-title":"Cancer Lett."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e127456","DOI":"10.1172\/jci.insight.127456","article-title":"Urine TNF-\u03b1 and IL-9 for Clinical Diagnosis of Acute Interstitial Nephritis","volume":"4","author":"Moledina","year":"2019","journal-title":"JCI Insight"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chen, G., Liu, B., Li, H., Mai, Z., Zhang, L., Li, M., Liu, L., Chen, S., Chen, J., and Liu, Y. (2020). Ethnicity-Stratified Analysis of the Association between TNF-\u03b1 Genetic Polymorphisms and Acute Kidney Injury: A Systematic Review and Me-ta-Analysis. Biomed. Res. Int., 2020.","DOI":"10.1155\/2020\/5262351"},{"key":"ref_44","first-page":"351","article-title":"YKL 40, a Mammalian Member of the Chitinase Family, Is a Matrix Protein of Specific Granules in Human Neutrophils","volume":"110","author":"Volck","year":"1998","journal-title":"Proc. Assoc. Am. Physicians"},{"key":"ref_45","first-page":"5","article-title":"YKL 40\u2014A Novel Biomarker in Clinical Practice?","volume":"51","author":"Kazakova","year":"2009","journal-title":"Folia Med."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Blazevic, N., Rogic, D., Pelajic, S., Miler, M., Glavcic, G., Ratkajec, V., Vrkljan, N., Bakula, D., Hrabar, D., and Pavic, T. (2024). YKL-40 as a Biomarker in Various Inflammatory Diseases: A Review. Biochem. Med., 34.","DOI":"10.11613\/BM.2024.010502"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1681\/ASN.2012060579","article-title":"Chitinase-like protein Brp-39\/YKL-40 modulates the renal response to ischemic injury and pre-dicts delayed allograft function","volume":"24","author":"Schmidt","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1080\/00365510410003057","article-title":"Distribution and Determinants of Serum Creatinine in the General Population: The Hordaland Health Study","volume":"64","author":"Vikse","year":"2004","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bufkin, K.B., and Silva, J. (2024). The XpressCard Point-of-Care Test for Human Neutrophil Gelatinase-Associated Lipocalin Enhances the Predic-tion of Acute Kidney Injury. J. Clin. Med., 13.","DOI":"10.3390\/jcm13247564"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Meersch, M., Schmidt, C., Van Aken, H., Martens, S., Rossaint, J., Singbartl, K., G\u00f6rlich, D., Kellum, J.A., and Zarbock, A. (2014). Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0093460"}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1775\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T10:15:43Z","timestamp":1759313743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/61\/10\/1775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,1]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["medicina61101775"],"URL":"https:\/\/doi.org\/10.3390\/medicina61101775","relation":{},"ISSN":["1648-9144"],"issn-type":[{"value":"1648-9144","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,1]]}}}