Laboratory Investigation

Kidney International (1989) 36, 240–248; doi:10.1038/ki.1989.186

Plasma lipids and acyltransferase activities in experimental nephrotic syndrome

Teresa L Sestak1, Nahid Alavi1 and Papasani V Subbaiah1,1

1Rush Medical College, Departments of Medicine and Biochemistry, Chicago, Illinois, USA

Correspondence: P V Subbaiah PhD, Section of Endocrinology and Metabolism, Rush Medical College, 1653 West Congress Parkway, Chicago, Illinois 60612, USA.

1Present address: Department of Medicine, Section of Nephrology, University of Illinois at Chicago, Chicago, Illinois.

Received 14 October 1988; Revised 26 January 1989; Accepted 29 March 1989.

Top

Abstract

Plasma lipids and acyltransferase activities in experimental nephrotic syndrome. Lecithin:cholesterol acyltransferase (LCAT) and lysolecithin acyltransferase (LAT) are two activities carried out by the same plasma enzyme, but require different apoprotein activators. The LCAT reaction takes place primarily on high density lipoproteins (HDL) and is activated by serum albumin, whereas LAT takes place on low density lipoproteins (LDL) and is inhibited by albumin. In nephrotic syndrome (NS), the levels of serum albumin are reduced, whereas the LDL levels are increased, and therefore, the ratio of LAT/LCAT activities should be increased. To test this hypothesis, we estimated the lipid levels and the two enzyme activities in experimental NS induced in rats by the injection of anti-FxlA antibody (passive Heymann nephritis). As found in other nephrotic conditions, the plasma lipid levels rose progressively as the proteinuria increased and the serum albumin concentration declined. In addition, the ratio of LAT/LCAT activities increased by about fourfold after nine days of induction of nephritis. The LCAT activity correlated positively and the LAT activity negatively with serum albumin levels. The esterified cholesterol correlated positively with LCAT activity in normal rats but negatively in nephrotic animals, indicating that most of the cholesteryl esters in NS may be non-LCAT derived. The free cholesterol/lecithin ratio, a known risk factor for atherosclerosis, increased significantly in nephrotic rats. Furthermore, since the increase in the LAT activity produces more disaturated lecithins, another putative risk factor, the cumulative risk of coronary heart disease may be increased in long-term NS.

Top

References

  1. Valeri A, Gelfand J, Blum C, Appel GB: Treatment of hyperlipidemia of the nephrotic syndrome: A controlled trial. Am J Kidney Dis 8:388–396, 1986
  2. Diamant S, Shafrir E: Lipogenesis in aminonucleoside-induced nephrotic syndrome. Biochim Biophys Acta 360:241–251, 1974
  3. Jungst D, Caselmann WH, Kutschera P, Weisweiler P: Relation of hyperlipidemia in serum and loss of HDL in urine in the nephrotic syndrome. Clin Chim Acta 168:159–167, 1987
  4. Miller CJ, Miller NE: Plasma high density lipoprotein concentration and development of ischemic heart disease. Lancet i:16, 1975
  5. Berlyne GM, Mallick NP: Ischemic heart disease as a complication of nephrotic syndrome. Lancet 2:399–400, 1969 | PubMed |
  6. Wass V, Cameron JS: Cardiovascular disease and the nephrotic syndrome: The other side of the coin. Nephron 27:58–61, 1981
  7. Glomset JA: The plasma lecithin:cholesterol acyltransferase reaction. J Lipid Res 9:155–167, 1968 | PubMed | ISI | ChemPort |
  8. Subbaiah PV, Albers JJ, Chen CH, Bagdade JD: Low density lipoprotein-activated lysolecithin acylation by human plasma lecithin-cholesterol acyltransferase. J Biol Chem 255:9275–9280, 1980
  9. Subbaiah PV, Chen CH, Bagdade JD, Albers JJ: Substrate specificity of plasma lysolecithin acyltransferase and the molecular species of lecithin formed by the reaction. J Biol Chem 260:5308–5314, 1985
  10. Gershfeld NL: Selective phospholipid adsorption and atherosclerosis. Science 204:506–509, 1979
  11. Gherardi E, Calandra S: Plasma and urinary lipids and lipoproteins during the development of nephrotic syndrome induced in the rat by puromycin aminonucleoside. Biochim Biophys Acta 710:188–196, 1981
  12. Singh AK, Makker SP: The distribution and molecular presentation of the brush border antigen of Heymann nephritis in various rat tissues. Clin Exp Immunol 60:579–585, 1985
  13. Kuksis A, Myher JJ, Geher K, Jones GJL, Breckenridge WC, Feather T, Hewitt D, Little JA: Decreased plasma phosphati-dylcholine/free cholesterol ratio as an indicator of risk for ischemic vascular disease. Arteriosclerosis 2:296–302, 1982
  14. Zamlauski-Tucker MJ, Van Lieu JB, Noble B: Pathophysiology of the kidney in rats with Heymann nephritis. Kidney Int 28:504–512, 1985
  15. Bradford MM: A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254, 1976 | Article | PubMed | ISI | ChemPort |
  16. Doumas BT, Watson WA, Biggs HG: Albumin standards and the measurement of serum albumin with bromcresol green. Clin Chim Acta 31:87–96, 1971 | Article | PubMed | ISI | ChemPort |
  17. Subbaiah PV: Lysolecithin acyltransferase of human plasma: Assay and characterization of enzyme activity. Meth Enzymol 129:790–797, 1986
  18. Bligh ED, Dyer WJ: A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917, 1959 | PubMed | ISI | ChemPort |
  19. Stokke KT, Norum KR: Determination of lecithin:cholesterol acyltransfer in human blood plasma. Scand J Clin Lab Invest 27:21–27, 1971
  20. Marinetti GV: Chromatographic separation, identification, and analysis of phosphatides. J Lipid Res 3:1–20, 1962 | ISI | ChemPort |
  21. Singh AK, Schwartz MM: Nephritogenicity and immunocyto-chemical localization of the 70-kilodalton glycoprotein subunit (gp 70) of Heymann antigen. Clin Immunol Immunopathol 48:61–77, 1988
  22. Cabana VG, Siegel JN, Sabesin SM: Effects of the acute phase response upon the concentration and density distribution of lipids and apolipoproteins. J Lipid Res 30:39–49, 1989
  23. Snedecor GW, Cochran WG: Statistical Methods, 6th ed. Ames, Iowa, Iowa State University Press, 1976
  24. Chan MK, Persaud JW, Ramdial L, Varghese Z, Sweny P, Moorhead JF: Hyperlipidemia in untreated nephrotic syndrome. Clin Chim Acta 117:317–323, 1981 | PubMed |
  25. Robbins SL, Cotran RS, Kumar V: Pathologic Basis of Disease, 3rd ed. Philadelphia, PA, WB Saunders and Co., 1984, pp. 1011–1018
  26. Dieplinger H, Schoenfeld PY, Fielding CJ: Plasma choiesterol metabolism in end-stage renal disease. Differences between treatment by hemodialysis or peritoneal dialysis. J Clin Invest 77:1071–1083, 1986 | PubMed | ISI | ChemPort |
  27. Ueno K, Sakuma N, Kawaguchi M, Fujinami T, Okuyama H: Selectivity and contribution of lecithin:cholesterol acyltransferase to plasma cholesterol ester formation. J Biochem 99:541–547, 1986
  28. Glomset JA: Lecithin:cholesterol acyltransferase. An exercise in comparative biology. Progr Biochem Pharmacol 15:41–66, 1979
  29. Gidez LI, Roheim DS, Eder HA: Effect of diet on the cholesterol ester composition of liver and of plasma lipoproteins in the rat. J Lipid Res 6:377–382, 1965
  30. Cohen SL, Cramp DG, Lewis AD, Tickner TR: The mechanism of hyperlipidemia in nephrotic syndrome-role of low albumin and the LCAT reaction. Clin Chim Acta 104:393–400, 1980
  31. Mallick NP, Short CO: The nephrotic syndrome and ischaemic heart disease. Nephron 27:54–57, 1981

Extra navigation

.
ADVERTISEMENT