{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:12Z","timestamp":1792789512775,"version":"4.5.0"},"reference-count":30,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"108 Military Central Hospital, Hanoi, Vietnam","award":["2021.89.32"],"award-info":[{"award-number":["2021.89.32"]}],"id":[{"id":"https:\/\/ror.org\/04k25m262","id-type":"ROR","asserted-by":"crossref"}]},{"award":["2021.89.32"],"award-info":[{"award-number":["2021.89.32"]}],"id":[{"id":"https:\/\/ror.org\/04k25m262","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>High-intensity physical exercise can induce temporary renal hemodynamic strain and subclinical tubular injury, yet the exact dose\u2013response relationship remains poorly defined. This study investigated the relationship between exercise intensity and urinary liver-type fatty acid-binding protein (L-FABP) concentrations, a sensitive marker of proximal tubular stress, to identify an exploratory intensity threshold. We conducted an observational cohort study of 285 healthy young men undergoing a routine 20 min physical training session. Exercise intensity was quantified as metabolic equivalents of task (METs) using wearable accelerometers, and urinary L-FABP was measured pre-exercise and 30 min post-exercise. Post-exercise urinary L-FABP concentrations increased significantly from baseline (median, 1.89 vs. 0.90 \u00b5g\/gCr; p &lt; 0.001). Restricted cubic splines confirmed a nonlinear dose\u2013response relationship (p for nonlinearity &lt; 0.001) with an estimated breakpoint at 6.76 METs (95% CI, 5.67 to 7.12). Below 6.76 METs, exercise intensity was not significantly associated with post-exercise L-FABP (\u03b2 = 0.068, p = 0.358), whereas above this threshold, L-FABP escalated rapidly (\u03b2 = 0.491, p &lt; 0.001). In conclusion, exercise intensity nonlinearly correlates with proximal renal tubular stress in young men. The 6.76 MET threshold represents an exploratory breakpoint marking an inflection zone beyond which exercise-associated subclinical renal tubular stress accelerates.<\/jats:p>","DOI":"10.3390\/ijms27198539","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:11:23Z","timestamp":1790248283000},"page":"8539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Nonlinear Dose\u2013Response Association Between Exercise Intensity and Urinary Liver-Type Fatty Acid-Binding Protein in Young Men: A Piecewise Threshold Analysis"],"prefix":"10.3390","volume":"27","author":[{"given":"Hoa Do","family":"Thanh","sequence":"first","affiliation":[{"name":"108 Military Central Hospital, No. 1 Tran Hung Dao Str., Hai Ba Trung Dist., Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4813-5805","authenticated-orcid":false,"given":"Duan Duc","family":"Le","sequence":"additional","affiliation":[{"name":"108 Military Central Hospital, No. 1 Tran Hung Dao Str., Hai Ba Trung Dist., Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Tuan Nguyen","family":"Anh","sequence":"additional","affiliation":[{"name":"108 Military Central Hospital, No. 1 Tran Hung Dao Str., Hai Ba Trung Dist., Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuong Nguyen","family":"Thai","sequence":"additional","affiliation":[{"name":"108 Military Central Hospital, No. 1 Tran Hung Dao Str., Hai Ba Trung Dist., Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghi Nguyen","family":"Hai","sequence":"additional","affiliation":[{"name":"108 Military Central Hospital, No. 1 Tran Hung Dao Str., Hai Ba Trung Dist., Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8136-1320","authenticated-orcid":false,"given":"Duong Le","family":"Xuan","sequence":"additional","affiliation":[{"name":"108 Military Central Hospital, No. 1 Tran Hung Dao Str., Hai Ba Trung Dist., Hanoi 100000, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1159\/000515022","article-title":"Effects of Exercise on Acute Kidney Injury Biomarkers and the Potential Influence of Fluid Intake","volume":"76","author":"Juett","year":"2020","journal-title":"Ann. Nutr. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Guo, C., Cui, Y., Jiao, M., Yao, J., Zhao, J., Tian, Y., Dong, J., and Liao, L. (2024). Crosstalk between proximal tubular epithelial cells and other interstitial cells in tubulointerstitial fibrosis after renal injury. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1256375"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1053\/j.ajkd.2012.10.016","article-title":"Performance of urinary liver-type fatty acid-binding protein in acute kidney injury: A meta-analysis","volume":"61","author":"Susantitaphong","year":"2013","journal-title":"Am. J. Kidney Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s41100-017-0107-x","article-title":"Urinary excretion of liver-type fatty acid-binding protein reflects the severity of sepsis","volume":"3","author":"Sato","year":"2017","journal-title":"Ren. Replace. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1007\/s10157-025-02641-8","article-title":"Efficacy of urinary [TIMP-2]\u22c5[IGFBP7], L-FABP, and NGAL levels for predicting community-acquired acute kidney injury in Japanese patients: A single-center, prospective cohort study","volume":"29","author":"Inotani","year":"2025","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3387","DOI":"10.1053\/j.jvca.2025.08.020","article-title":"Urinary Liver-Type Fatty Acid Binding Protein as a Postoperative Marker of Acute Kidney Injury in Patients Undergoing EndovascularAortic Aneurysm Repair","volume":"39","author":"Abelardo","year":"2025","journal-title":"J. Cardiothorac. Vasc. Anesth."},{"key":"ref_8","first-page":"114","article-title":"The Role of Urine Liver Fatty Acid Binding Protein in Early Detection of Acute Kidney Injury in Septic Patient","volume":"8","author":"Hartomuljono","year":"2021","journal-title":"Egypt. J. Crit. Care Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejim.2019.10.025","article-title":"Creatinine: From physiology to clinical application","volume":"72","author":"Kashani","year":"2020","journal-title":"Eur. J. Intern. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/S0002-9440(10)63384-6","article-title":"Urinary excretion of fatty acid-binding protein reflects stress overload on the proximal tubules","volume":"165","author":"Kamijo","year":"2004","journal-title":"Am. J. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1097\/CCM.0b013e3181eedac0","article-title":"Urinary L-type fatty acid-binding protein as a new biomarker of sepsis complicated with acute kidney injury","volume":"38","author":"Doi","year":"2010","journal-title":"Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s13300-025-01731-w","article-title":"Urinary L-FABP: A Novel Biomarker for Evaluating Diabetic Nephropathy Onset and Progression. A Narrative Review","volume":"16","author":"Satta","year":"2025","journal-title":"Diabetes Ther."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Okuda, H., Asai, H., Yamamoto, K., Miyazaki, K., Fukushima, H., and Saeki, K. (2025). Prognosis prediction by urinary L-FABP in ICU patients admitted from the emergency department: A single-center, historical cohort study. Res. Sq.","DOI":"10.21203\/rs.3.rs-7161428\/v1"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wo\u0142yniec, W., Ratkowski, W., Renke, J., and Renke, M. (2020). Changes in Novel AKI Biomarkers after Exercise. A Systematic Review. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165673"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Knechtle, B., Scheer, V., Nikolaidis, P.T., Thuany, M., Chl\u00edbkov\u00e1, D., Forte, P., Leite, L.B., Weiss, K., Rosemann, T., and Duric, S. (2026). The Comrades Marathon: A narrative review of physiological responses and health implications in the world\u2019s oldest ultra-marathon. Front. Physiol., 17.","DOI":"10.3389\/fphys.2026.1811456"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1152\/japplphysiol.00289.2025","article-title":"Hypohydration augments the acute increase in urinary biomarkers of kidney injury following the 100-mile Western States Endurance Run","volume":"139","author":"Linder","year":"1985","journal-title":"J. Appl. Physiol."},{"key":"ref_17","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_18","doi-asserted-by":"crossref","unstructured":"Poussel, M., Touz\u00e9, C., Allado, E., Frimat, L., Hily, O., Thilly, N., Rousseau, H., Vauthier, J.-C., and Chenuel, B. (2020). Ultramarathon and Renal Function: Does Exercise-Induced Acute Kidney Injury Really Exist in Common Conditions?. Front. Sports Act. Living, 1.","DOI":"10.3389\/fspor.2019.00071"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Bouscaren, N., Millet, G.Y., and Racinais, S. (2019). Heat Stress Challenges in Marathon vs. Ultra-Endurance Running. Front. Sports Act. Living, 1.","DOI":"10.3389\/fspor.2019.00059"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Hoppel, F., Calabria, E., Pesta, D., Kantner-Rumplmair, W., Gnaiger, E., and Burtscher, M. (2019). Physiological and Pathophysiological Responses to Ultramarathon Running in Non-elite Runners. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.01300"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/sms.13869","article-title":"Effect of marathon and ultra-marathon on inflammation and iron homeostasis","volume":"31","author":"Kaufmann","year":"2021","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/sms.13618","article-title":"Incremental short maximal exercise increases urinary liver-type fatty acid-binding protein in adults without CKD","volume":"30","author":"Kosaki","year":"2020","journal-title":"Scand. J. Med. Sci. Sports"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Tominaga, T., Ma, S., Sugama, K., Kanda, K., Omae, C., Choi, W., Hashimoto, S., Aoyama, K., Yoshikai, Y., and Suzuki, K. (2021). Changes in Urinary Biomarkers of Organ Damage, Inflammation, Oxidative Stress, and Bone Turnover Following a 3000-m Time Trial. Antioxidants, 10.","DOI":"10.3390\/antiox10010079"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Pelliccia, A., Heidbuchel, H., Corrado, D., B\u00f6rjesson, M., Sharma, S., Pelliccia, A., Heidbuchel, H., Corrado, D., Borjesson, M., and Sharma, S. (2019). Physiology of exercise. The ESC Textbook of Sports Cardiology, Oxford University Press.","DOI":"10.1093\/med\/9780198779742.001.0001"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e15420","DOI":"10.14814\/phy2.15420","article-title":"The moderate-intensity continuous exercise maintains renal blood flow and does not impair the renal function","volume":"10","author":"Kawakami","year":"2022","journal-title":"Physiol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"57434","DOI":"10.12775\/QS.2025.37.57434","article-title":"Kidney Function and Extreme Endurance Races: Risks, Mechanisms, and Preventing Strategies","volume":"37","author":"Kulbacka","year":"2025","journal-title":"Qual. Sport"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1152\/japplphysiol.00392.2022","article-title":"Renal blood flow during exercise: Understanding its measurement with Doppler ultrasound","volume":"134","author":"Rocha","year":"2023","journal-title":"J. Appl. Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"355","DOI":"10.34067\/KID.0004772020","article-title":"Proximal Tubular Oxidative Metabolism in Acute Kidney Injury and the Transition to CKD","volume":"2","author":"Schaub","year":"2021","journal-title":"Kidney360"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1038\/ki.2008.106","article-title":"Renal L-type fatty acid-binding protein mediates the bezafibrate reduction of cisplatin-induced acute kidney injury","volume":"73","author":"Negishi","year":"2008","journal-title":"Kidney Int."},{"key":"ref_30","first-page":"635","article-title":"Urinary L-type fatty acid binding protein (L-FABP) as a new urinary biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan","volume":"61","author":"Ichikawa","year":"2013","journal-title":"Rinsho Byori"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8539\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:51:55Z","timestamp":1790614315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8539"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":30,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198539"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198539","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}