REDUCTION OF PLASMA APOLIPOPROTEIN-B BY EFFECTIVE REMOVAL OF CIRCULATING GLYCATION DERIVATIVES IN UREMIA

Patients with diabetes and renal insufficiency (Db/ESRD), a group subj ect to accelerated atherosclerosis exhibit marked increases in the lev els of circulating, glycation-derived reactive substances, termed adva nced glycation endproducts (AGEs). These products have bean previously shown to react covalently with apoliprotein B (ApoB) to form AGE-ApoB , a modification that results in delayed low density lipoprotein (LDL) clearance and possibly to dyslipidemia. Because the effect of hemodia lysis on AGE removal was shown to be unsatisfactory, based on single i ntradialytic studies, we examined the effect of long-term hemodialysis therapy on serum AGE-ApoB levels, as well as on total serum ApoB of 2 5 Db/ESRD patients treated by two types of hemodialysis filters, the F resenius Inc. F8, as the low flux (LF), or high-flux polysulfone AN69 (HF) for two months using an AGE-specific ELISA. At the end of eight w eeks, circulating AGE-ApoB levels were reduced significantly (by 35%) from baseline (P = 0.039) in patients treated by HF compared to a mode st 16% reduction noted in patients treated by LF (P = 0.05) N = 12, (P = 0.047). Of note, total plasma ApoB was reduced by 27% from baseline (P = 0.02) in patients treated by HF compared to a 6% reduction noted in those treated with LF (P = 0.8). In vitro comparison of AGE mass b alance, and mass adsorption by the different filters revealed that the higher efficiency of HF filter was due to greater adsorption. The ass ociation of reduced AGE-ApoB levels with a decrease in total circulati ng ApoB by HF and not by LF dialysis suggests: (1) a causal link betwe en AGE clearance and dyslipidemia in diabetic ESRD, and, (2) that more efficient modes of renal replacement treatment and AGE removal could significantly benefit clinical outcome.