{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T10:22:24Z","timestamp":1756462944235,"version":"3.37.3"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100010198","name":"Ministerio de Econom\u00eda, Industria y Competitividad, Gobierno de Espa\u00f1a","doi-asserted-by":"crossref","award":["PTA2017-14093-I"],"award-info":[{"award-number":["PTA2017-14093-I"]}],"id":[{"id":"10.13039\/501100010198","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI18\/00255"],"award-info":[{"award-number":["PI18\/00255"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A large proportion of end-stage renal disease (ESRD) patients under long-term haemodialysis, have persistent anaemia and require high doses of recombinant human erythropoietin (rhEPO). However, the underlying mechanisms of renal anaemia have not been fully elucidated in these patients. In this study, we will be focusing on anaemia and plasma proteins in ESRD patients on high-flux haemodialysis (HF) and on-line haemodiafiltration (HDF), to investigate using two proteomic approaches if patients undergoing these treatments develop differences in their plasma protein composition and how this could be related to their anaemia. The demographic and biochemical data revealed that HDF patients had lower anaemia and much lower rhEPO requirements than HF patients. Regarding their plasma proteomes, HDF patients had increased levels of a protein highly similar to serotransferrin, trypsin-1 and immunoglobulin heavy constant chain alpha-1, and lower levels of alpha-1 antitrypsin, transthyretin, apolipoproteins E and C-III, and haptoglobin-related protein. Lower transthyretin levels in HDF patients were further confirmed by transthyretin-peptide quantification and western blot detection. Since ESRD patients have increased transthyretin, a protein that can aggregate and inhibit transferrin endocytosis and erythropoiesis, our finding that HDF patients have lower transthyretin and lower anaemia suggests that the decrease in transthyretin plasma levels would allow an increase in transferrin endocytosis, contributing to erythropoiesis. Thus, transthyretin could be a critical actor for anaemia in ESRD patients and a novel player for haemodialysis adequacy.<\/jats:p>","DOI":"10.1038\/s41598-020-72104-5","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T10:03:40Z","timestamp":1601373820000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Proteomic analysis of plasma proteins of high-flux haemodialysis and on-line haemodiafiltration patients reveals differences in transthyretin levels related with anaemia"],"prefix":"10.1038","volume":"10","author":[{"given":"Emma","family":"Mart\u00ednez-Alonso","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Alc\u00e1zar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emilio","family":"Camafeita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milagros","family":"Fern\u00e1ndez-Lucas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Ru\u00edz-Roso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Alc\u00e1zar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,29]]},"reference":[{"key":"72104_CR1","doi-asserted-by":"publisher","first-page":"A7","DOI":"10.1053\/j.ajkd.2018.01.002","volume":"71","author":"R Saran","year":"2018","unstructured":"Saran, R. et al. US Renal Data System 2017 annual data report: epidemiology of kidney disease in the United States. Am. J. Kidney. Dis. 71, A7 (2018).","journal-title":"Am. J. Kidney. Dis."},{"key":"72104_CR2","doi-asserted-by":"crossref","unstructured":"Palmer, S. C. et al. High-flux versus low-flux membranes for end-stage kidney disease. Cochrane Database Syst Rev, CD005016 (2012).","DOI":"10.1002\/14651858.CD005016.pub2"},{"key":"72104_CR3","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1681\/ASN.V11122344","volume":"11","author":"RA Ward","year":"2000","unstructured":"Ward, R. A., Schmidt, B., Hullin, J., Hillebrand, G. F. & Samtleben, W. A comparison of on-line hemodiafiltration and high-flux hemodialysis: a prospective clinical study. J. Am. Soc. Nephrol. 11, 2344\u20132350 (2000).","journal-title":"J. Am. Soc. Nephrol."},{"key":"72104_CR4","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1093\/ndt\/gfx277","volume":"33","author":"F Locatelli","year":"2018","unstructured":"Locatelli, F. et al. Mortality risk in patients on hemodiafiltration versus hemodialysis: a \u201creal-world\u201d comparison from the DOPPS. Nephrol. Dial Transplant. 33, 683\u2013689 (2018).","journal-title":"Nephrol. Dial Transplant."},{"key":"72104_CR5","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.semnephrol.2006.06.001","volume":"26","author":"M Nangaku","year":"2006","unstructured":"Nangaku, M. & Eckardt, K. U. Pathogenesis of renal anemia. Semin. Nephrol. 26, 261\u2013268 (2006).","journal-title":"Semin. Nephrol."},{"key":"72104_CR6","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1159\/000077409","volume":"24","author":"RG Langlois","year":"2004","unstructured":"Langlois, R. G. et al. Serum protein profile alterations in hemodialysis patients. Am. J. Nephrol. 24, 268\u2013274 (2004).","journal-title":"Am. J. Nephrol."},{"key":"72104_CR7","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1080\/0886022X.2018.1491406","volume":"40","author":"S Han","year":"2018","unstructured":"Han, S. et al. Proteomics investigation of the changes in serum proteins after high- and low-flux hemodialysis. Ren. Fail. 40, 506\u2013513 (2018).","journal-title":"Ren. Fail."},{"key":"72104_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.2147\/TCRM.S150824","volume":"14","author":"M Bonomini","year":"2018","unstructured":"Bonomini, M., Pieroni, L., Di Liberato, L., Sirolli, V. & Urbani, A. Examining hemodialyzer membrane performance using proteomic technologies. Ther. Clin. Risk Manag. 14, 1\u20139 (2018).","journal-title":"Ther. Clin. Risk Manag."},{"key":"72104_CR9","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1681\/ASN.V451205","volume":"4","author":"JT Daugirdas","year":"1993","unstructured":"Daugirdas, J. T. Second generation logarithmic estimates of single-pool variable volume Kt\/V: an analysis of error. J. Am. Soc. Nephrol. 4, 1205\u20131213 (1993).","journal-title":"J. Am. Soc. Nephrol."},{"key":"72104_CR10","doi-asserted-by":"publisher","first-page":"iii53","DOI":"10.1093\/ndt\/gfy218","volume":"33","author":"PJ Blankestijn","year":"2018","unstructured":"Blankestijn, P. J., Grooteman, M. P., Nube, M. J. & Bots, M. L. (2018) Clinical evidence on haemodiafiltration. Nephrol Dial Transplant 33, iii53\u2013iii58","journal-title":"Nephrol Dial Transplant"},{"key":"72104_CR11","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1093\/ndt\/14.5.1202","volume":"14","author":"F Maduell","year":"1999","unstructured":"Maduell, F. et al. Change from conventional haemodiafiltration to on-line haemodiafiltration. Nephrol. Dial Transplant. 14, 1202\u20131207 (1999).","journal-title":"Nephrol. Dial Transplant."},{"key":"72104_CR12","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1515\/CCLM.2002.226","volume":"40","author":"NJ Cano","year":"2002","unstructured":"Cano, N. J. Metabolism and clinical interest of serum transthyretin (prealbumin) in dialysis patients. Clin. Chem. Lab. Med. 40, 1313\u20131319 (2002).","journal-title":"Clin. Chem. Lab. Med."},{"key":"72104_CR13","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.mcna.2016.09.005","volume":"101","author":"PG Fraenkel","year":"2017","unstructured":"Fraenkel, P. G. Anemia of inflammation: a review. Med. Clin. N. Am. 101, 285\u2013296 (2017).","journal-title":"Med. Clin. N. Am."},{"key":"72104_CR14","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.semnephrol.2016.02.001","volume":"36","author":"T Ganz","year":"2016","unstructured":"Ganz, T. & Nemeth, E. Iron balance and the role of hepcidin in chronic kidney disease. Semin. Nephrol. 36, 87\u201393 (2016).","journal-title":"Semin. Nephrol."},{"key":"72104_CR15","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1186\/s12882-017-0688-1","volume":"18","author":"A Mikhail","year":"2017","unstructured":"Mikhail, A. et al. Renal association clinical practice guideline on Anaemia of Chronic Kidney Disease. BMC Nephrol. 18, 345 (2017).","journal-title":"BMC Nephrol."},{"key":"72104_CR16","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.biocel.2017.02.002","volume":"85","author":"VH Fong","year":"2017","unstructured":"Fong, V. H., Wong, S. & Vieira, A. Disruption of endocytic transport by transthyretin aggregates. Int. J. Biochem. Cell Biol. 85, 102\u2013105 (2017).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"72104_CR17","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1515\/bmc-2013-0038","volume":"5","author":"M Vieira","year":"2014","unstructured":"Vieira, M. & Saraiva, M. J. Transthyretin: a multifaceted protein. Biomol. Concepts 5, 45\u201354 (2014).","journal-title":"Biomol. Concepts"},{"key":"72104_CR18","doi-asserted-by":"crossref","unstructured":"IV. NKF-K\/DOQI Clinical Practice Guidelines for Anemia of Chronic Kidney Disease: Update 2000. American Journal of Kidney Diseases 37, S182-S238 (2001).","DOI":"10.1016\/S0272-6386(01)70008-X"},{"issue":"110","key":"72104_CR19","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1152\/japplphysiol.00665.2010","volume":"1985","author":"B Christensen","year":"2011","unstructured":"Christensen, B. et al. Novel serum biomarkers for erythropoietin use in humans: a proteomic approach. J. Appl. Physiol. 1985(110), 149\u2013156 (2011).","journal-title":"J. Appl. Physiol."},{"issue":"Suppl 1","key":"72104_CR20","doi-asserted-by":"publisher","first-page":"S21","DOI":"10.1111\/hdi.12556","volume":"21","author":"AE Gaweda","year":"2017","unstructured":"Gaweda, A. E. Markers of iron status in chronic kidney disease. Hemodial. Int. 21(Suppl 1), S21\u2013S27 (2017).","journal-title":"Hemodial. Int."},{"key":"72104_CR21","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.1002\/pmic.200700214","volume":"7","author":"C Cid","year":"2007","unstructured":"Cid, C. et al. Proteomic characterization of protein phosphatase 1 complexes in ischemia-reperfusion and ischemic tolerance. Proteomics 7, 3207\u20133218 (2007).","journal-title":"Proteomics"},{"key":"72104_CR22","doi-asserted-by":"publisher","first-page":"2856","DOI":"10.1038\/nprot.2006.468","volume":"1","author":"A Shevchenko","year":"2006","unstructured":"Shevchenko, A., Tomas, H., Havlis, J., Olsen, J. V. & Mann, M. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat. Protoc. 1, 2856\u20132860 (2006).","journal-title":"Nat. Protoc."},{"key":"72104_CR23","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1007\/s00216-003-2057-0","volume":"376","author":"D Suckau","year":"2003","unstructured":"Suckau, D. et al. A novel MALDI LIFT-TOF\/TOF mass spectrometer for proteomics. Anal. Bioanal. Chem. 376, 952\u2013965 (2003).","journal-title":"Anal. Bioanal. Chem."},{"key":"72104_CR24","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1074\/mcp.M700239-MCP200","volume":"7","author":"S Martinez-Bartolome","year":"2008","unstructured":"Martinez-Bartolome, S. et al. Properties of average score distributions of SEQUEST: the probability ratio method. Mol. Cell Proteom. 7, 1135\u20131145 (2008).","journal-title":"Mol. Cell Proteom."},{"key":"72104_CR25","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1021\/pr4006958","volume":"13","author":"P Navarro","year":"2014","unstructured":"Navarro, P. et al. General statistical framework for quantitative proteomics by stable isotope labeling. J. Proteome Res. 13, 1234\u20131247 (2014).","journal-title":"J. Proteome Res."},{"key":"72104_CR26","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1074\/mcp.M115.055905","volume":"15","author":"F Garcia-Marques","year":"2016","unstructured":"Garcia-Marques, F. et al. A novel systems-biology algorithm for the analysis of coordinated protein responses using quantitative proteomics. Mol. Cell Proteom. 15, 1740\u20131760 (2016).","journal-title":"Mol. Cell Proteom."},{"key":"72104_CR27","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1093\/bioinformatics\/bty815","volume":"35","author":"M Trevisan-Herraz","year":"2019","unstructured":"Trevisan-Herraz, M. et al. SanXoT: a modular and versatile package for the quantitative analysis of high-throughput proteomics experiments. Bioinformatics 35, 1594\u20131596 (2019).","journal-title":"Bioinformatics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72104-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72104-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72104-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T19:52:25Z","timestamp":1670356345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72104-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,29]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["72104"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-72104-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2020,9,29]]},"assertion":[{"value":"28 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16029"}}