EFFECT OF ONCOTIC PRESSURE ON APOLIPOPROTEIN-A-I METABOLISM IN THE RAT

The nephrotic syndrome is characterized by reduced plasma albumin and colloid osmotic pressure (pi), urinary protein loss and hyperlipidemia . High-density lipoprotein (HDL) and the level of apo A-I, the princip al apolipoprotein in HDL, is increased in nephrotic rats and rats with hereditary analbuminemia (NAR)-animals with virtually no albumin in p lasma and reduced plasma pi, but without proteinuria, suggesting that urinary protein loss is not responsible for increased plasma apo A-I l evels. We conducted these studies to determine the mechanism responsib le for increased plasma apo A-I levels in the nephrotic syndrome and N AR and to determine whether reduced plasma pi or albumin was responsib le for increased apo A-I. We first measured the clearance of I-125 apo A-I HDL in NAR and rats with passive Heymann nephritis (HN) compared with normal Sprague Dawley (SD) control. Both the clearance of apo A-I and fractional apo A-I turnover rate (FTR) were significantly reduced both in HN (7.40 +/- 2.18% plasma pool/hr) and NAR (5.63 +/- 1.12) co mpared with SD (9.87 +/- 0.75). Total apo A-I turnover rate, which in steady state equals apo A-I synthesis rate, was also significantly inc reased in both HN (487 +/- 127 mu g/100 g body weight/hr) and NAR (253 +/- 16), compared with SD (216 +/- 19). Thus decreased apo A-I catabo lism and increased synthesis both contributed to increased apo A-I lev els in HN and NAR. We then infused either hyperoncotic human albumin o r ficoll into two additional groups of HN for days in quantities suffi cient to maintain plasma rr within the normal range. Both cholesterol and apo A-I levels decreased to normal, even though proteinuria persis ted, Thus apo A-I levels were increased both in HN and NAR as a result of both increased synthesis and reduced catabolism in response to red uced plasma pi. Neither hypoalbuminemia nor proteinuria were necessary . (C) 1995 by the National Kidney Foundation, Inc.