TY - JOUR
T1 - Increased levels of ficolin-1 and of C3dg are independently associated with high risk of infection in patients with chronic kidney disease
T2 - a prospective cohort study
AU - Sagedal, Solbjørg
AU - Hovd, Markus
AU - Åsberg, Anders
AU - Mollnes, Tom Eirik
AU - Klingenberg, Olav
AU - Heldal, Torbjørn Fossum
AU - Witczak, Bartlomiej J
AU - Hejlesen, Trine Korsgaard
AU - Troldborg, Anne
AU - Thiel, Steffen
N1 - Copyright © 2025 Sagedal, Hovd, Åsberg, Mollnes, Klingenberg, Heldal, Witczak, Hejlesen, Troldborg and Thiel.
PY - 2025
Y1 - 2025
N2 - Background and hypothesis: Infection is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). The complement system provides crucial first-line defense against pathogens. Mannose-binding lectin (MBL), ficolins (1, 2 and 3), and collectin-LK 1 (CL-LK) are pattern recognition molecules (PRMs) of the lectin pathway (LP) that recognize microbial surfaces and activate complement. C3dg is a complement cleavage fragment indicating complement activation. The aim of the study was to investigate whether levels of PRMs and C3dg are associated with the risk of significant infections requiring hospitalization in patients with CKD. Methods: This prospective cohort study included 518 patients ≥18 years with CKD (eGFR<60 mL/min/1.73 m2), consecutively recruited between 2008-2022. About half (270/518) were in dialysis at inclusion. None of the patients were previously transplanted with any organ or stem cells. The primary endpoint was non-access-related infections requiring hospitalization. Patients were followed until kidney transplantation or death or until 31.12.2024. Plasma concentrations of the biomarkers were measured at inclusion. Time-to-event analyses using Cox regression were employed to assess associations with infection, adjusting for age, sex, diabetes, dialysis status, and dialysis vintage. Results: During a median (interquartile range [IQR]) time of follow-up of 1.24 (0.49-2.76) years, 182 patients (35%) were hospitalized due to non-access infection. Higher baseline levels of ficolin-1 and C3dg were independently associated with infection risk, HR 3.05, 95% CI 1.25-7.43, p=0.01 and HR 2.97, 95% CI 1.37-6.44, p=0.006, respectively, for each log10 unit increase. In multivariable models including all biomarkers, only C3dg remained independently associated with infection (HR 2.81, 95% CI 1.23-6.43, p=0.01). Conclusions: High levels of complement activation (C3dg) and ficolin-1 were independently associated with increased infection risk in patients with CKD. A dysregulated complement activation rather than PRM deficiency seems to be a key pathogenic mechanism resulting in increased infection risk in advanced CKD.
AB - Background and hypothesis: Infection is a leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). The complement system provides crucial first-line defense against pathogens. Mannose-binding lectin (MBL), ficolins (1, 2 and 3), and collectin-LK 1 (CL-LK) are pattern recognition molecules (PRMs) of the lectin pathway (LP) that recognize microbial surfaces and activate complement. C3dg is a complement cleavage fragment indicating complement activation. The aim of the study was to investigate whether levels of PRMs and C3dg are associated with the risk of significant infections requiring hospitalization in patients with CKD. Methods: This prospective cohort study included 518 patients ≥18 years with CKD (eGFR<60 mL/min/1.73 m2), consecutively recruited between 2008-2022. About half (270/518) were in dialysis at inclusion. None of the patients were previously transplanted with any organ or stem cells. The primary endpoint was non-access-related infections requiring hospitalization. Patients were followed until kidney transplantation or death or until 31.12.2024. Plasma concentrations of the biomarkers were measured at inclusion. Time-to-event analyses using Cox regression were employed to assess associations with infection, adjusting for age, sex, diabetes, dialysis status, and dialysis vintage. Results: During a median (interquartile range [IQR]) time of follow-up of 1.24 (0.49-2.76) years, 182 patients (35%) were hospitalized due to non-access infection. Higher baseline levels of ficolin-1 and C3dg were independently associated with infection risk, HR 3.05, 95% CI 1.25-7.43, p=0.01 and HR 2.97, 95% CI 1.37-6.44, p=0.006, respectively, for each log10 unit increase. In multivariable models including all biomarkers, only C3dg remained independently associated with infection (HR 2.81, 95% CI 1.23-6.43, p=0.01). Conclusions: High levels of complement activation (C3dg) and ficolin-1 were independently associated with increased infection risk in patients with CKD. A dysregulated complement activation rather than PRM deficiency seems to be a key pathogenic mechanism resulting in increased infection risk in advanced CKD.
KW - Adult
KW - Aged
KW - Biomarkers/blood
KW - Female
KW - Ficolins
KW - Humans
KW - Infections/etiology
KW - Lectins/blood
KW - Male
KW - Middle Aged
KW - Prospective Studies
KW - Renal Insufficiency, Chronic/complications
KW - Risk Factors
KW - chronic kidney disease
KW - infection
KW - C3dg
KW - lectin pathway
KW - pattern recognition molecules
KW - ficolin-1
KW - complement
UR - https://www.scopus.com/pages/publications/105018956778
U2 - 10.3389/fimmu.2025.1645347
DO - 10.3389/fimmu.2025.1645347
M3 - Journal article
C2 - 41103429
SN - 1664-3224
VL - 16
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1645347
ER -