Complement C3 and incident hospitalization due to chronic kidney disease: a population-based cohort study

Area of Science:

• Nephrology
• Immunology
• Epidemiology

Background:

• Circulating C3 complement protein is implicated in diabetes and hypertension, key drivers of chronic kidney disease (CKD).
• C3 activation pathways are suspected contributors to various renal pathologies.
• Understanding C3's role in CKD pathogenesis is crucial for identifying at-risk individuals.

Purpose of the Study:

• To investigate the association between elevated C3 concentrations and the risk of hospitalization due to CKD in the general population.
• To determine if diabetes and hypertension mediate the relationship between C3 levels and CKD hospitalization.
• To explore C3 as a potential biomarker for CKD incidence.

Main Methods:

• A cohort of 4552 participants from the Malmö Diet and Cancer study, free of prior CKD hospitalization, had baseline plasma C3 measured.
• Cox proportional hazards regression models were used to analyze the incidence of first CKD hospitalization over a mean follow-up of 19.2 years.
• Multivariate adjustments and sensitivity analyses incorporated traditional CKD risk factors like diabetes, blood pressure, and C-reactive protein.

Main Results:

• During follow-up, 94 participants were hospitalized for CKD.
• After adjusting for multiple variables, individuals in higher quartiles of C3 showed a significantly increased hazard ratio for CKD hospitalization (p-trend = 0.003).
• The association between C3 levels and CKD hospitalization remained robust across sensitivity analyses.

Conclusions:

• Elevated C3 concentration is independently associated with an increased risk of first hospitalization due to CKD in the general population.
• The observed link between C3 and CKD hospitalization is not solely explained by hyperglycemia or hypertension.
• C3 may serve as a valuable biomarker for predicting CKD incidence and progression.