{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:28:00Z","timestamp":1785421680521,"version":"3.56.0"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"crossref","award":["384\/2024"],"award-info":[{"award-number":["384\/2024"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"crossref","award":["384\/2025"],"award-info":[{"award-number":["384\/2025"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"crossref","award":["450\/2024"],"award-info":[{"award-number":["450\/2024"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010621","name":"Medical University of Lublin","doi-asserted-by":"crossref","award":["450\/2025"],"award-info":[{"award-number":["450\/2025"]}],"id":[{"id":"10.13039\/501100010621","id-type":"DOI","asserted-by":"crossref"}]},{"award":["384\/2024"],"award-info":[{"award-number":["384\/2024"]}],"id":[{"id":"https:\/\/ror.org\/016f61126","id-type":"ROR","asserted-by":"publisher"}]},{"award":["384\/2025"],"award-info":[{"award-number":["384\/2025"]}],"id":[{"id":"https:\/\/ror.org\/016f61126","id-type":"ROR","asserted-by":"publisher"}]},{"award":["450\/2024"],"award-info":[{"award-number":["450\/2024"]}],"id":[{"id":"https:\/\/ror.org\/016f61126","id-type":"ROR","asserted-by":"publisher"}]},{"award":["450\/2025"],"award-info":[{"award-number":["450\/2025"]}],"id":[{"id":"https:\/\/ror.org\/016f61126","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Certain metabolites of the tryptophan-kynurenine (Trp-KYN) pathway, which are primarily cleared via tubular transport, have been linked to end-stage kidney disease (ESKD). Uromodulin\u2014a protein expressed exclusively in the kidneys\u2014is a key regulator of renal structure and function, as well as a direct marker of tubular health. This preliminary study explores the hypothesis that serum uromodulin correlates with Trp-KYN metabolites, potentially revealing new pathophysiological pathways in patients undergoing kidney replacement therapy (KRT). Given the link between serum uromodulin, Trp-KYN metabolites, and tubular function, we examined their correlation in KRT patients. Furthermore, we assessed how various clinical and dialysis parameters influence serum uromodulin levels. Methods: A total of 64 stable patients from a single dialysis center receiving hemodialysis (HD) or hemodiafiltration (HDF) were enrolled. Pre- and post-dialysis concentrations of uromodulin, Trp, KYN, kynurenic acid (KYNA), 3-hydroxykynurenine (3-OHKYN), and their reduction ratios (RRs) were established. High-performance liquid chromatography (HPLC) was used to estimate the KYN pathway metabolite levels, whereas uromodulin concentration was measured using an immunoenzymatic assay. Results: Detectable serum uromodulin was found in only 30 patients. This group was predominantly male (p &lt; 0.001) and characterized by shorter dialysis vintage (p &lt; 0.001), a higher prevalence of residual kidney function (RKF) (p = 0.001) and diabetes mellitus (p = 0.028), higher pre-dialysis serum phosphorus levels (p = 0.015), and more frequent use of loop diuretics (p = 0.004). Furthermore, univariate analysis revealed significantly higher pre-dialysis (p = 0.004) and post-dialysis (p = 0.025) serum Trp concentrations in the uromodulin-positive group. Pre-dialysis serum uromodulin concentration correlated positively with pre-dialysis Trp level (p &lt; 0.001) and negatively with the pre-dialysis KYN\/Trp ratio (p = 0.008), but not with other metabolites that are also subject to tubular transport mechanisms. Post-dialysis uromodulin levels correlated positively only with post-dialysis Trp level (p = 0.005). Patients treated with HDF had significantly higher RR for uromodulin than those treated with HD (p = 0.01). Conclusions: The presented data indicate that serum uromodulin levels are correlated with RKF. Additionally, the presence of detectable serum uromodulin may indicate reduced immunological activation, leading to diminished activity within the Trp-KYN pathway.<\/jats:p>","DOI":"10.3390\/jcm15103743","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:26:37Z","timestamp":1778689597000},"page":"3743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uromodulin and Tryptophan Metabolite Clearance in Hemodialyzed Patients"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5251-7763","authenticated-orcid":false,"given":"Izabela","family":"Zakrocka","sequence":"first","affiliation":[{"name":"Department of Nephrology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma\u0142gorzata","family":"Kozio\u0142","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Wi\u0119ckowska-Dero\u0144","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwia","family":"Boczkowska","sequence":"additional","affiliation":[{"name":"Department of Holistic Care and Management in Nursing, Medical University of Lublin, 20-081 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Kloc","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-2626","authenticated-orcid":false,"given":"Tomasz","family":"Kocki","sequence":"additional","affiliation":[{"name":"Institute of Health Sciences, The John Paul II Catholic University of Lublin, Konstantyn\u00f3w 1F Street, 20-708 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Olender","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Medical University of Lublin, 20-093 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-528X","authenticated-orcid":false,"given":"Ewa M.","family":"Urba\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Za\u0142uska","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2945-2946","authenticated-orcid":false,"given":"Andreas","family":"Kronbichler","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1093\/ndt\/gfaf024","article-title":"Haemodiafiltration versus High-Flux Haemodialysis\u2014A Consensus Statement from the EuDial Working Group of the ERA","volume":"40","author":"Battaglia","year":"2025","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Canaud, B., Strippoli, G., and Davenport, A. (2025). High-Volume Hemodiafiltration Versus High-Flux Hemodialysis: A Narrative Review for the Clinician. J. Clin. Med., 14.","DOI":"10.3390\/jcm14082614"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1007\/BF00272616","article-title":"Tamm-Horsfall Protein-MRNA Synthesis Is Localized to the Thick Ascending Limb of Henle\u2019s Loop in Rat Kidney","volume":"94","author":"Bachmann","year":"1990","journal-title":"Histochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.kint.2018.04.021","article-title":"Uromodulin Is Expressed in the Distal Convoluted Tubule, Where It Is Critical for Regulation of the Sodium Chloride Cotransporter NCC","volume":"94","author":"Tokonami","year":"2018","journal-title":"Kidney Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/ndt\/gfy394","article-title":"Uromodulin (Tamm-Horsfall Protein): Guardian of Urinary and Systemic Homeostasis","volume":"35","author":"Micanovic","year":"2020","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1093\/ndt\/gfae008","article-title":"Uromodulin Biology","volume":"39","author":"Karagiannidis","year":"2024","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/MNH.0000000000000885","article-title":"Uromodulin: More than a Marker for Chronic Kidney Disease Progression","volume":"32","author":"LaFavers","year":"2023","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"eaaw3639","DOI":"10.1126\/scitranslmed.aaw3639","article-title":"Circulating Uromodulin Inhibits Systemic Oxidative Stress by Inactivating the TRPM2 Channel","volume":"11","author":"LaFavers","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1681\/ASN.2014070664","article-title":"Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis","volume":"26","author":"Micanovic","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1681\/ASN.2017040409","article-title":"Tamm-Horsfall Protein Regulates Mononuclear Phagocytes in the Kidney","volume":"29","author":"Micanovic","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"150","DOI":"10.2215\/CJN.06390420","article-title":"What Does Uromodulin Do?","volume":"16","author":"Kipp","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/ndt\/gfac187","article-title":"Uromodulin and Its Association with Urinary Metabolites: The German Chronic Kidney Disease Study","volume":"38","author":"Sekula","year":"2023","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"616","DOI":"10.2215\/CJN.11780919","article-title":"Association of Serum Uromodulin with Death, Cardiovascular Events, and Kidney Failure in CKD","volume":"15","author":"Steubl","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100536","DOI":"10.1016\/j.xkme.2022.100536","article-title":"Serum Uromodulin and All-Cause Mortality in Peritoneal Dialysis Patients: A Chinese Cohort Study","volume":"4","author":"Steubl","year":"2022","journal-title":"Kidney Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1186\/s12967-026-07758-2","article-title":"IDO Family: The Metabolic Crossroads Connecting Immunity, Nerves and Tumors","volume":"24","author":"Wang","year":"2026","journal-title":"J. Transl. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.kint.2025.11.022","article-title":"Meta-Organismal Tryptophan Metabolism: An Appealing Therapeutic Target in CKD-MBD","volume":"109","author":"Fernandes","year":"2026","journal-title":"Kidney Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"F199","DOI":"10.1152\/ajprenal.00019.2024","article-title":"Chronic Infusion of the Tryptophan Metabolite, Kynurenine Increases Mean Arterial Pressure in Male Sprague Dawley Rats","volume":"327","author":"Irsik","year":"2024","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.ekir.2025.02.024","article-title":"Uncovering the Link Between Kynurenic Acid Pathway and Kidney Failure","volume":"10","author":"Liabeuf","year":"2025","journal-title":"Kidney Int. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"100575","DOI":"10.1016\/j.jbc.2021.100575","article-title":"Coordinate Regulation of Systemic and Kidney Tryptophan Metabolism by the Drug Transporters OAT1 and OAT3","volume":"296","author":"Granados","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"632","DOI":"10.5301\/ijao.5000456","article-title":"Theoretical Basis for and Improvement of Daugirdas\u2019 Second Generation Formula for Single-Pool Kt\/V","volume":"38","author":"Sternby","year":"2015","journal-title":"Int. J. Artif. Organs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.jchromb.2010.01.006","article-title":"Optimization of Zn2+-Containing Mobile Phase for Simultaneous Determination of Kynurenine, Kynurenic Acid and Tryptophan in Human Plasma by High Performance Liquid Chromatography","volume":"878","author":"Zhao","year":"2010","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/S0378-4347(00)83925-0","article-title":"Quantification of 3-Hydroxykynurenine in Brain by High-Performance Liquid Chromatography and Electrochemical Detection","volume":"428","author":"Heyes","year":"1988","journal-title":"J. Chromatogr."},{"key":"ref_23","first-page":"628","article-title":"No Change in Corrected Beta 2-Microglobulin Concentration after Cuprophane Haemodialysis","volume":"1","author":"Wehle","year":"1987","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1159\/000503805","article-title":"Rationale and Strategies for Preserving Residual Kidney Function in Dialysis Patients","volume":"50","author":"Li","year":"2019","journal-title":"Am. J. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1093\/cvr\/cvaa081","article-title":"Circulating Uromodulin Inhibits Vascular Calcification by Interfering with Pro-Inflammatory Cytokine Signalling","volume":"117","author":"Alesutan","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e1302","DOI":"10.34067\/KID.0000000000000197","article-title":"Healthy Women Have Higher Systemic Uromodulin Levels: Identification of Uromodulin as an Estrogen Responsive Gene","volume":"4","author":"Nanamatsu","year":"2023","journal-title":"Kidney360"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"\u017deravica, R., Ilin\u010di\u0107, B., Buri\u0107, D., Jakovljevi\u0107, A., Crnobrnja, V., Ili\u0107, D., and Papuga, M.V. (2024). Relationship Between Serum Uromodulin as a Marker of Kidney Damage and Metabolic Status in Patients with Chronic Kidney Disease of Non-Diabetic Etiology. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252011159"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"30200","DOI":"10.1074\/jbc.M111.222968","article-title":"Activation of the Bumetanide-Sensitive Na+, K+, 2Cl\u2212 Cotransporter (NKCC2) Is Facilitated by Tamm-Horsfall Protein in a Chloride-Sensitive Manner","volume":"286","author":"Mutig","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1161\/HYPERTENSIONAHA.113.01423","article-title":"Validation of Uromodulin as a Candidate Gene for Human Essential Hypertension","volume":"63","author":"Graham","year":"2014","journal-title":"Hypertension"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1053\/j.ajkd.2023.05.017","article-title":"Associations of Baseline and Longitudinal Serum Uromodulin with Kidney Failure and Mortality: Results from the African American Study of Kidney Disease and Hypertension (AASK) Trial","volume":"83","author":"Chen","year":"2024","journal-title":"Am. J. Kidney Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"196","DOI":"10.2478\/v10039-010-0015-6","article-title":"Kynurenine Pathway\u2014A New Link between Endothelial Dysfunction and Carotid Atherosclerosis in Chronic Kidney Disease Patients","volume":"55","author":"Pawlak","year":"2010","journal-title":"Adv. Med. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.thromres.2007.01.011","article-title":"Tissue Factor and Urokinase-Type Plasminogen Activator System Are Related to the Presence of Cardiovascular Disease in Hemodialysis Patients","volume":"120","author":"Pawlak","year":"2007","journal-title":"Thromb. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1080\/0886022X.2016.1209389","article-title":"Serum Indoleamine 2,3 Dioxygenase and Tryptophan and Kynurenine Ratio Using the UPLC-MS\/MS Method, in Patients Undergoing Peritoneal Dialysis, Hemodialysis, and Kidney Transplantation","volume":"38","author":"Yilmaz","year":"2016","journal-title":"Ren. Fail."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.34067\/KID.0000000000000185","article-title":"Removal of Middle Molecules and Dialytic Albumin Loss: A Cross-over Study of Medium Cutoff and High-Flux Membranes with Hemodialysis and Hemodiafiltration","volume":"4","author":"Osuna","year":"2023","journal-title":"Kidney360"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1053\/j.jrn.2019.12.003","article-title":"Differences and Effects of Metabolic Fate of Individual Amino Acid Loss in High-Efficiency Hemodialysis and Hemodiafiltration","volume":"30","author":"Murtas","year":"2020","journal-title":"J. Ren. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gagel, A., Wiesen, G., Stuard, S., and Canaud, B. (2026). Advances in Membrane, Dialyzer Design, and Related Monitoring Technologies for Hemodiafiltration: Translating Bench-Side Innovations to Bedside Applications. J. Clin. Med., 15.","DOI":"10.20944\/preprints202602.0325.v1"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1093\/ndt\/gfw422","article-title":"Serum Uromodulin-a Marker of Kidney Function and Renal Parenchymal Integrity","volume":"33","author":"Scherberich","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1093\/ndt\/gft345","article-title":"Determination of Uromodulin in Human Urine: Influence of Storage and Processing","volume":"29","author":"Youhanna","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/s41581-024-00881-7","article-title":"Advances in Uromodulin Biology and Potential Clinical Applications","volume":"20","author":"Nanamatsu","year":"2024","journal-title":"Nat. Rev. Nephrol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/10\/3743\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:28:20Z","timestamp":1778819300000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/10\/3743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,13]]},"references-count":39,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["jcm15103743"],"URL":"https:\/\/doi.org\/10.3390\/jcm15103743","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,13]]}}}