{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T15:54:47Z","timestamp":1776614087898,"version":"3.51.2"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Lublin, Poland","award":["384\/2024"],"award-info":[{"award-number":["384\/2024"]}]},{"name":"Medical University of Lublin, Poland","award":["384\/2025"],"award-info":[{"award-number":["384\/2025"]}]},{"name":"Medical University of Lublin, Poland","award":["450\/2024"],"award-info":[{"award-number":["450\/2024"]}]},{"name":"Medical University of Lublin, Poland","award":["450\/2025"],"award-info":[{"award-number":["450\/2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic kidney disease (CKD) and kidney failure significantly reduce patients\u2019 quality of life and markedly increase cardiovascular risk and overall mortality. Disturbed metabolism of tryptophan (Trp) through kynurenine (KYN) pathway was implicated as an important factor in kidney damage and its complications. However, the expression of genes coding crucial enzymes of KYN pathway was not examined so far. The goal of the present study was to analyze the expression of Ido (indoleamine-2,3-dioxygenase), Kat1 (kynurenine aminotransferase 1), Kat2 (kynurenine aminotransferase 2), and Kmo (kynurenine-3-monooxygenase) genes in patients undergoing kidney failure with kidney replacement therapy (KFRT) treatment with either hemodiafiltration (HDF) or hemodialysis (HD) in relation to selected clinical and dialysis parameters. Our data imply that Ido, Kat1, and Kmo gene expression does not differ between KFRT patients with analyzed comorbidities, vascular access types, or diuresis occurrence. However, Ido and Kmo gene expression correlated with pre-dialysis concentration or reduction ratio (RR) of selected metabolites. Interestingly, patients treated with HDF manifested lower Kmo gene expression in comparison with patients treated by HD. Our study suggests that epigenetic factors do not exert noticeable impact on the KYN pathway enzymes expression in patients with KFRT. The advantageous effect of HDF vs. HD towards the KYN pathway genes expression has potential therapeutic implications, as it may reflect superiority of the former method in KFRT patients.<\/jats:p>","DOI":"10.3390\/ijms27031313","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T15:04:46Z","timestamp":1769612686000},"page":"1313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Impact of Clinical Variables and Dialysis Modality on Kynurenine Pathway Enzymes Expression"],"prefix":"10.3390","volume":"27","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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9945-7446","authenticated-orcid":false,"given":"Katarzyna","family":"Wicha-Komsta","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Kloc","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wojciech","family":"Za\u0142uska","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Medical University of Lublin, 20-090 Lublin, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"ref_1","unstructured":"(2025). GBD 2023 Kidney Failure with Replacement Therapy Collaborators. Global, Regional, and National Prevalence of Kidney Failure with Replacement Therapy and Associated Aetiologies, 1990\u20132023: A Systematic Analysis for the Global Burden of Disease Study 2023. Lancet Glob. Health, 13, e1378\u2013e1395."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1016\/j.ekir.2023.07.020","article-title":"Residual Kidney Function and Cause-Specific Mortality Among Incident Hemodialysis Patients","volume":"8","author":"Okazaki","year":"2023","journal-title":"Kidney Int. Rep."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Peth\u0151, \u00c1.G., F\u00fcl\u00f6p, T., Orosz, P., Sz\u00e9n\u00e1si, G., Tapolyai, M., and D\u00e9zsi, L. (2025). Increased Cardiovascular Mortality in Hemodialysis: The Role of Chronic Inflammation, Complement Activation, and Non-Biocompatibility. Toxins, 17.","DOI":"10.3390\/toxins17070345"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.2215\/CJN.02660221","article-title":"Classification of Uremic Toxins and Their Role in Kidney Failure","volume":"16","author":"Rosner","year":"2021","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Stuard, S., Maddux, F.W., and Canaud, B. (2025). Why High-Volume Post-Dilution Hemodiafiltration Should Be the New Standard in Dialysis Care: A Comprehensive Review of Clinical Outcomes and Mechanisms. J. Clin. Med., 14.","DOI":"10.20944\/preprints202506.0652.v1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1007\/s00011-024-01878-5","article-title":"Tryptophan Catabolism via the Kynurenine Pathway Regulates Infection and Inflammation: From Mechanisms to Biomarkers and Therapies","volume":"73","author":"Zhang","year":"2024","journal-title":"Inflamm. Res."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ball, H.J., Fedelis, F.F., Bakmiwewa, S.M., Hunt, N.H., and Yuasa, H.J. (2014). Tryptophan-Catabolizing Enzymes\u2014Party of Three. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00485"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.2741\/4363","article-title":"Tryptophan-Kynurenine Pathway Is Dysregulated in Inflammation, and Immune Activation","volume":"20","author":"Wang","year":"2015","journal-title":"Front. Biosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s43440-021-00329-w","article-title":"Kynurenine Pathway in Kidney Diseases","volume":"74","author":"Zakrocka","year":"2022","journal-title":"Pharmacol. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Bolanos-Palmieri, P., Schenk, H., B\u00e4hre, H., Schroder, P., Staggs, L., Haller, H., and Schiffer, M. (2025). Kynurenine Pathway Dysregulation Impairs Podocyte Morphology and Bioenergetics In Vitro and Leads to Glomerular Dysfunction. FASEB J., 39.","DOI":"10.1096\/fj.202502175R"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1093\/ndt\/gfn739","article-title":"Increased Indoleamine 2,3-Dioxygenase (IDO) Activity and Elevated Serum Levels of Tryptophan Catabolites in Patients with Chronic Kidney Disease: A Possible Link between Chronic Inflammation and Uraemic Symptoms","volume":"24","author":"Schefold","year":"2009","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","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_14","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.thromres.2009.04.011","article-title":"Kynurenines and Oxidative Status Are Independently Associated with Thrombomodulin and von Willebrand Factor Levels in Patients with End-Stage Renal Disease","volume":"124","author":"Pawlak","year":"2009","journal-title":"Thromb. Res."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fryc, J., and Naumnik, B. (2021). Thrombolome and Its Emerging Role in Chronic Kidney Diseases. Toxins, 13.","DOI":"10.3390\/toxins13030223"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"El Chamieh, C., Larabi, I.A., Alencar De Pinho, N., Lambert, O., Combe, C., Fouque, D., Frimat, L., Jacquelinet, C., Laville, M., and Laville, S. (2024). Study of the Association between Serum Levels of Kynurenine and Cardiovascular Outcomes and Overall Mortality in Chronic Kidney Disease. Clin. Kidney J., 17.","DOI":"10.1093\/ckj\/sfad248"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.clnu.2025.01.028","article-title":"Serum Tryptophan and Kynurenine Levels and Risk of Heart Failure among Patients with Chronic Kidney Disease","volume":"47","author":"Mohiti","year":"2025","journal-title":"Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1007\/s00018-017-2504-2","article-title":"Abnormal Kynurenine Pathway of Tryptophan Catabolism in Cardiovascular Diseases","volume":"74","author":"Song","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Debnath, S., Velagapudi, C., Redus, L., Thameem, F., Kasinath, B., Hura, C.E., Lorenzo, C., Abboud, H.E., and O\u2019Connor, J.C. (2017). Tryptophan Metabolism in Patients with Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers. Int. J. Tryptophan Res., 10.","DOI":"10.1177\/1178646917694600"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"van Gelder, M.K., Middel, I.R., Vernooij, R.W.M., Bots, M.L., Verhaar, M.C., Masereeuw, R., Grooteman, M.P., Nub\u00e9, M.J., van den Dorpel, M.A., and Blankestijn, P.J. (2020). Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome. Toxins, 12.","DOI":"10.3390\/toxins12040234"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mor, A., Kalaska, B., and Pawlak, D. (2020). Kynurenine Pathway in Chronic Kidney Disease: What\u2019s Old, What\u2019s New, and What\u2019s Next?. Int. J. Tryptophan Res., 13.","DOI":"10.1177\/1178646920954882"},{"key":"ref_22","first-page":"175","article-title":"Peripheral Distribution of Kynurenine Metabolites and Activity of Kynurenine Pathway Enzymes in Renal Failure","volume":"54","author":"Pawlak","year":"2003","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"379","DOI":"10.3109\/1354750X.2013.790074","article-title":"Serum Levels and Activity of Indoleamine2,3-Dioxygenase and Tryptophanyl-TRNA Synthetase and Their Association with Disease Severity in Patients with Chronic Kidney Disease","volume":"18","author":"Bao","year":"2013","journal-title":"Biomarkers"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"25261","DOI":"10.18632\/oncotarget.15705","article-title":"Peripheral Kynurenine\/Tryptophan Ratio Is Not a Reliable Marker of Systemic Indoleamine 2,3-Dioxygenase: A Lesson Drawn from Patients on Hemodialysis","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1080\/08830185.2020.1836176","article-title":"Indoleamine 2,3-Dioxygenase: A Professional Immunomodulator and Its Potential Functions in Immune Related Diseases","volume":"41","author":"Heidari","year":"2022","journal-title":"Int. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neulet.2008.06.007","article-title":"Induction of Indolamine 2,3-Dioxygenase and Kynurenine 3-Monooxygenase in Rat Brain Following a Systemic Inflammatory Challenge: A Role for IFN-Gamma?","volume":"441","author":"Connor","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1111\/bph.17407","article-title":"Chronic Stress Induces Behavioural Changes through Increased Kynurenic Acid by Downregulation of Kynurenine-3-Monooxygenase with Microglial Decline","volume":"182","author":"Hasegawa","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1053\/j.ajkd.2010.03.020","article-title":"Association of Residual Urine Output with Mortality, Quality of Life, and Inflammation in Incident Hemodialysis Patients: The Choices for Healthy Outcomes in Caring for End-Stage Renal Disease (CHOICE) Study","volume":"56","author":"Shafi","year":"2010","journal-title":"Am. J. Kidney Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Gon\u00e7alves, G.T., Santos, L.M.D.M., Figueiredo, P.H.S., Freitas, J.D.P.C., Santos, J.M., Santos, J.N.V., Junior, F.A.D.S., Alves, F.L., Brand\u00e3o, V.G., and Maciel, E.H.B. (2025). High Level of Soluble Tumor Necrosis Factor Receptors Is Associated with Lower Residual Diuresis Volume in Patients on Hemodialysis: An Exploratory Study. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0320019"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Cheng, L., Min, Y., Tu, C., Wan, S., Zhu, Q., Chen, J., Qiu, W., Jiang, N., and Li, H. (2025). The Prognosis of Maintenance Hemodialysis Patients With Various Types of Vascular Access in Hemodialysis Centers in Wuhan: A Retrospective Cohort Study. Int. J. Nephrol., 2025.","DOI":"10.1155\/ijne\/5865205"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Venegas-Ram\u00edrez, J., Hern\u00e1ndez-Fuentes, G.A., Palomares, C.S., Diaz-Martinez, J., Navarro-Cuellar, J.I., Calvo-Soto, P., Duran, C., Tapia-Vargas, R., Esp\u00edritu-Mojarro, A.C., and Figueroa-Guti\u00e9rrez, A. (2025). Vascular Access Type and Survival Outcomes in Hemodialysis Patients: A Seven-Year Cohort Study. Medicina, 61.","DOI":"10.3390\/medicina61040584"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1053\/j.jrn.2021.11.002","article-title":"Prognostic Value of the Malnutrition-Inflammation Score in Hospitalization and Mortality on Long-Term Hemodialysis","volume":"32","author":"Aguiar","year":"2022","journal-title":"J. Ren. Nutr."},{"key":"ref_33","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_34","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. Transpl."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","unstructured":"Zarobkiewicz, M., Kowalska, W., Chocholska, S., Tomczak, W., Szyma\u0144ska, A., Morawska, I., Wojciechowska, A., and Bojarska-Junak, A. (2020). High M-MDSC Percentage as a Negative Prognostic Factor in Chronic Lymphocytic Leukaemia. Cancers, 12.","DOI":"10.3390\/cancers12092614"},{"key":"ref_37","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 Analyt. Technol. Biomed. Life Sci."},{"key":"ref_38","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_39","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"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1313\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T09:03:30Z","timestamp":1770195810000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/3\/1313"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["ijms27031313"],"URL":"https:\/\/doi.org\/10.3390\/ijms27031313","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]}}}