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Association between apolipoprotein A-IV concentrations and chronic kidney disease in two large population-based
S Stangl1, B Kollerits1, C Lamina1
1Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Medical University of Innsbruck, Innsbruck, Austria.
Insights
High plasma apolipoprotein A-IV (apoA-IV) levels are linked to reduced kidney function in the general population. This finding suggests apoA-IV may serve as an early indicator of declining kidney function, even before other chronic kidney disease (CKD) risk factors appear.
Area of Science:
- Cardiovascular and Metabolic Science
- Nephrology
- Biochemistry
Background:
- Apolipoprotein A-IV (apoA-IV) is recognized for its anti-atherogenic and antioxidative properties.
- Elevated plasma apoA-IV levels are observed in individuals with primary chronic kidney disease (CKD) or renal failure.
- The relationship between apoA-IV and kidney function in the general population remains under-investigated.
Purpose of the Study:
- To investigate the association between plasma apoA-IV concentrations and kidney function in two large, population-based cohorts.
- To determine if apoA-IV can serve as an early marker for impaired kidney function.
Main Methods:
- Plasma apoA-IV concentrations were measured in the KORA F3 (n=3159) and KORA F4 (n=3061) studies.
- Chronic kidney disease (CKD) was defined using serum creatinine-estimated glomerular filtration rate (eGFR) and/or urine albumin-to-creatinine ratio.
- Statistical analyses included linear mixed models and logistic regression to assess associations and improve discrimination of low eGFR.
Main Results:
- A significant association was found between higher apoA-IV concentrations and lower eGFR across quartiles in both cohorts.
- Elevated apoA-IV levels (third and fourth quartiles) were significantly associated with an increased likelihood of having an eGFR <60 mL/min/1.73 m².
- Including apoA-IV in risk models significantly improved the prediction of low eGFR (<60 mL/min/1.73 m²) beyond established CKD risk factors.
Conclusions:
- High plasma apoA-IV concentrations are strongly associated with reduced kidney function (low eGFR) in the general population.
- This association is independent of major CKD risk factors, suggesting apoA-IV's potential as an early biomarker.
- ApoA-IV may represent a novel, early indicator of impaired kidney function.
Background:
Apolipoprotein A-IV (apoA-IV) is an anti-atherogenic and antioxidative glycoprotein. Plasma apoA-IV levels are elevated in patients with primary chronic kidney disease (CKD) or renal failure. The association between apoA-IV and kidney function has not been investigated in the general population; therefore, we analysed this relationship in two large population-based cohorts.
Methods:
Plasma apoA-IV concentrations were measured in the Cooperative Health Research in the Region of Augsburg (KORA) F3 (n = 3159) and KORA F4 (n = 3061) studies. CKD was defined by the serum creatinine-estimated glomerular filtration rate (eGFR) and/or urine albumin-to-creatinine ratio.
Results:
Mean (±SD) apoA-IV concentration was 17.3 ± 4.7 mg dL(-1) in KORA F3 and 15.3 ± 4.3 mg dL(-1) in KORA F4. Fully adjusted linear mixed models revealed a significant association between apoA-IV concentration and lower eGFR in the third and fourth versus the first quartile of apoA-IV (β = -1.78 mL min(-1) /1.73 m², P = 0.0003 and β = -5.09 mL min(-1) /1.73 m², P = 2.83 × 10(-23) , respectively). ApoA-IV was significantly associated with an eGFR of <60 mL min(-1) /1.73 m², which was observed in 601 of the 6220 study participants [odds ratio (OR) 1.46, P = 0.03 and OR 3.47, P = 6.84 × 10(-15) for the third and fourth vs. the first quartile of apoA-IV, respectively]. Adding apoA-IV (fourth vs. first quartile) to the fully adjusted model significantly improved discrimination of eGFR <60 mL min(-1) /1.73 m² in KORA F3 [integrated discrimination improvement (IDI) 0.03, P = 1.30 × 10(-7) ] and KORA F4 (IDI 0.04, P = 1.32 × 10(-9) ) beyond classical risk factors for CKD.
Conclusion:
The present analysis in two population-based cohorts revealed that high plasma apoA-IV concentrations are strongly associated with low kidney function defined by eGFR independent of major CKD risk factors. ApoA-IV appears to be an early marker of impaired kidney function.
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