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Cystatin C proteoforms in chronic kidney disease

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 d...

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Autores principales: Dahl, Helene, Meyer, Klaus, Sandnes, Kristina, Welland, Natasha Lervaag, Arnesen, Iselin, Marti, Hans-Peter, Dierkes, Jutta, Lysne, Vegard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891521/
https://www.ncbi.nlm.nih.gov/pubmed/36724153
http://dx.doi.org/10.1371/journal.pone.0269436
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author Dahl, Helene
Meyer, Klaus
Sandnes, Kristina
Welland, Natasha Lervaag
Arnesen, Iselin
Marti, Hans-Peter
Dierkes, Jutta
Lysne, Vegard
author_facet Dahl, Helene
Meyer, Klaus
Sandnes, Kristina
Welland, Natasha Lervaag
Arnesen, Iselin
Marti, Hans-Peter
Dierkes, Jutta
Lysne, Vegard
author_sort Dahl, Helene
collection PubMed
description 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. Methods: 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’ records. Results: 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. Conclusion: 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.
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spelling pubmed-98915212023-02-02 Cystatin C proteoforms in chronic kidney disease Dahl, Helene Meyer, Klaus Sandnes, Kristina Welland, Natasha Lervaag Arnesen, Iselin Marti, Hans-Peter Dierkes, Jutta Lysne, Vegard PLoS One Research Article 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. Methods: 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’ records. Results: 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. Conclusion: 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. Public Library of Science 2023-02-01 /pmc/articles/PMC9891521/ /pubmed/36724153 http://dx.doi.org/10.1371/journal.pone.0269436 Text en © 2023 Dahl et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dahl, Helene
Meyer, Klaus
Sandnes, Kristina
Welland, Natasha Lervaag
Arnesen, Iselin
Marti, Hans-Peter
Dierkes, Jutta
Lysne, Vegard
Cystatin C proteoforms in chronic kidney disease
title Cystatin C proteoforms in chronic kidney disease
title_full Cystatin C proteoforms in chronic kidney disease
title_fullStr Cystatin C proteoforms in chronic kidney disease
title_full_unstemmed Cystatin C proteoforms in chronic kidney disease
title_short Cystatin C proteoforms in chronic kidney disease
title_sort cystatin c proteoforms in chronic kidney disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9891521/
https://www.ncbi.nlm.nih.gov/pubmed/36724153
http://dx.doi.org/10.1371/journal.pone.0269436
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