Apolipoprotein A-IV concentrations and clinical outcomes in a large chronic kidney disease cohort: Results from the GCKD study
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Published on: April 4, 2025
Johannes P Schwaiger1,2, Barbara Kollerits1, Inga Steinbrenner3
1Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.
Insights
Higher levels of apolipoprotein A-IV (apoA-IV) are linked to reduced inflammation and lower mortality risk in patients with chronic kidney disease (CKD). This suggests apoA-IV may be a key biomarker for cardiovascular outcomes in CKD patients.
Area of Science:
- Nephrology
- Cardiology
- Biochemistry
Background:
- Chronic kidney disease (CKD) is characterized by inflammation and high cardiovascular risk.
- Apolipoprotein A-IV (apoA-IV) possesses anti-inflammatory and anti-atherogenic properties.
- ApoA-IV levels increase in CKD patients.
Purpose of the Study:
- To investigate the association between apoA-IV levels and mortality and cardiovascular outcomes in CKD patients.
- To determine if apoA-IV is an independent risk marker in this population.
Main Methods:
- Prospective cohort study of 5141 Caucasian CKD patients.
- Measured apoA-IV levels and followed patients for a median of 6.5 years.
- Statistical modeling adjusted for major confounders to assess associations.
Main Results:
- Higher apoA-IV concentrations correlated with lower high-sensitivity C-reactive protein (hs-CRP) levels, despite more diabetes and lower eGFR.
- Each 10 mg/dl increase in apoA-IV was associated with reduced odds of prevalent cardiovascular disease (OR=0.80).
- Elevated apoA-IV significantly lowered risk for all-cause mortality (HR=0.81), major adverse cardiovascular events (HR=0.88), and heart failure hospitalizations (HR=0.84).
Conclusions:
- Elevated apoA-IV concentrations are linked to reduced inflammation in moderate CKD.
- ApoA-IV serves as an independent protective marker against mortality and adverse cardiovascular events in CKD patients.
Background:
Chronic kidney disease (CKD) represents a chronic proinflammatory state and is associated with very high cardiovascular risk. Apolipoprotein A-IV (apoA-IV) has antiatherogenic, antioxidative, anti-inflammatory and antithrombotic properties and levels increase significantly during the course of CKD.
Objectives:
We aimed to investigate the association between apoA-IV and all-cause mortality and cardiovascular outcomes in the German Chronic Kidney Disease study.
Methods:
This was a prospective cohort study including 5141 Caucasian patients with available apoA-IV measurements and CKD. The majority of the patients had an estimated glomerular filtration rate (eGFR) of 30-60 ml/min/1.73m2 or an eGFR >60 ml/min/1.73m2 in the presence of overt proteinuria. Median follow-up was 6.5 years. The association of apoA-IV with comorbidities at baseline and endpoints during follow-up was modelled adjusting for major confounders.
Results:
Mean apoA-IV concentrations of the entire cohort were 28.9 ± 9.8 mg/dl. Patients in the highest apoA-IV quartile had the lowest high-sensitivity C-reactive protein values despite the highest prevalence of diabetes, albuminuria and the lowest eGFR. Each 10 mg/dl higher apoA-IV translated into lower odds of prevalent cardiovascular disease (1289 cases, odds ratio = 0.80, 95% confidence interval [CI] 0.72-0.86, p = 0.0000003). During follow-up, each 10 mg/dl higher apoA-IV was significantly associated with a lower risk for all-cause mortality (600 cases, hazard ratio [HR] = 0.81, 95% CI 0.73-0.89, p = 0.00004), incident major adverse cardiovascular events (506 cases, HR = 0.88, 95% CI 0.79-0.99, p = 0.03) and death or hospitalizations due to heart failure (346 cases, HR = 0.84, 95% CI 0.73-0.96, p = 0.01).
Conclusions:
These data support a link between elevated apoA-IV concentrations and reduced inflammation in moderate CKD. ApoA-IV appears to be an independent risk marker for reduced all-cause mortality, cardiovascular events and heart failure in a large cohort of patients with CKD.
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