Cargando…

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...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario: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.