Association between apolipoprotein A-IV concentrations and chronic kidney disease in two large population-based cohorts: results from the KORA studies.

Abstract

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. 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. Mean (±SD) apoA-IV concentration was 17.3±4.7mgdL(-1) in KORA F3 and 15.3±4.3mgdL(-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=-1.78mLmin(-1) /1.73m², P=0.0003 and β=-5.09mLmin(-1) /1.73m², P=2.83×10(-23) , respectively). ApoA-IV was significantly associated with an eGFR of <60mLmin(-1) /1.73m², 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 <60mLmin(-1) /1.73m² 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. 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.