{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T18:01:41Z","timestamp":1791568901593,"version":"4.3.4"},"reference-count":25,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T00:00:00Z","timestamp":1675209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Bergen"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Cystatin C, a cysteine protease inhibitor, is used as a biomarker of renal function. It offers several advantages compared to creatinine, and formulas for the estimation of the glomerular filtration rate based on cystatin C have been developed. Recently, several proteoforms of cystatin C have been discovered, including an intact protein with a hydroxylated proline at the N-terminus, and N-terminal truncated forms. There is little knowledge about the biological significance of these proteoforms. <jats:bold>Methods<\/jats:bold>: Cross-sectional study of patients with different stages of chronic renal disease (pre-dialysis n = 53; hemodialysis n = 51, renal transplant n = 53). Measurement of cystatin C proteoforms by MALDI-TOF MS, assessment of medicine prescription using the first two levels of the Anatomical Therapeutic chemical system from patients\u2019 records. <jats:bold>Results<\/jats:bold>: Patients receiving hemodialysis had the highest cystatin C concentrations, followed by pre-dialysis patients and patients with a renal transplant. In all groups, the most common proteoforms were native cystatin C and CysC 3Pro-OH while the truncated forms made up 28%. The distribution of the different proteoforms was largely independent of renal function and total cystatin C. However, the use of corticosteroids (ATC-L02) and immunosuppressants (ATC-H04) considerably impacted the distribution of proteoforms. <jats:bold>Conclusion<\/jats:bold>: The different proteoforms of cystatin C increased proportionally with total cystatin C in patients with chronic kidney disease. Prescription of corticosteroids and immunosuppressants had a significant effect on the distribution of proteoforms. The biological significance of these proteoforms remains to be determined.<\/jats:p>","DOI":"10.1371\/journal.pone.0269436","type":"journal-article","created":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T19:03:16Z","timestamp":1675278196000},"page":"e0269436","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cystatin C proteoforms in chronic kidney disease"],"prefix":"10.1371","volume":"18","author":[{"given":"Helene","family":"Dahl","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Sandnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha Lervaag","family":"Welland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iselin","family":"Arnesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Peter","family":"Marti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0663-877X","authenticated-orcid":true,"given":"Jutta","family":"Dierkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vegard","family":"Lysne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,1]]},"reference":[{"key":"pone.0269436.ref001","doi-asserted-by":"crossref","first-page":"e0158765","DOI":"10.1371\/journal.pone.0158765","article-title":"Global Prevalence of Chronic Kidney Disease\u2014A Systematic Review and Meta-Analysis","volume":"11","author":"NR Hill","year":"2016","journal-title":"PLoS One"},{"key":"pone.0269436.ref002","first-page":"1","article-title":"KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"3","author":"KDIGO","year":"2013","journal-title":"Kidney Int Suppl"},{"key":"pone.0269436.ref003","doi-asserted-by":"crossref","first-page":"2093","DOI":"10.1111\/j.1600-6143.2011.03686.x","article-title":"Systematic review: Kidney transplantation compared with dialysis in clinically relevant outcomes","volume":"11","author":"M Tonelli","year":"2011","journal-title":"Am J Transplant"},{"key":"pone.0269436.ref004","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.2215\/CJN.06870909","article-title":"Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size","volume":"5","author":"WM Michels","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"pone.0269436.ref005","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.cca.2014.08.039","article-title":"Biomarkers of renal function, which and when?","volume":"438","author":"ME Wasung","year":"2015","journal-title":"Clin Chim Acta"},{"key":"pone.0269436.ref006","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1056\/NEJMoa1114248","article-title":"Estimating Glomerular Filtration Rate from Serum Creatinine and Cystatin C","volume":"367","author":"LA Inker","year":"2012","journal-title":"N Engl J Med"},{"key":"pone.0269436.ref007","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1515\/CCLM.2009.263","article-title":"Glomerular filtration rate measurement and prediction equations","volume":"47","author":"AA Soares","year":"2009","journal-title":"Clin Chem Lab Med"},{"key":"pone.0269436.ref008","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1056\/NEJMoa1214234","article-title":"Cystatin C versus Creatinine in Determining Risk Based on Kidney Function","volume":"369","author":"MG Shlipak","year":"2013","journal-title":"N Engl J Med"},{"key":"pone.0269436.ref009","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1080\/10408360490504934","article-title":"Biochemistry and clinical role of human cystatin C","author":"M Mussap","year":"2004","journal-title":"Critical Reviews in Clinical Laboratory Sciences"},{"key":"pone.0269436.ref010","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1042\/bj2730621","article-title":"Human cystatin C. 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