Clinical Investigation

Kidney International (1984) 25, 683–688; doi:10.1038/ki.1984.74

Plasma lipoproteins and lecithin:cholesterol acyltransferase distribution in patients on dialysis

Roger McLeod1, C Edward Reeve1 and Jiri Frohlich1

1Departments of Pathology and Medicine, University of British Columbia, Vancouver, British Columbia, Canada

Correspondence: Dr J Frohlich, Division of Clinical Chemistry, Department of Pathology, Shaughnessy Hospital, 4500 Oak Street, Vancouver, British Columbia V6H 3N1, Canada

Received 12 November 1982; Revised 15 September 1983.

Top

Abstract

Plasma lipoproteins and lecithin:cholesterol acyltransferase distribution in patients on dialysis. Plasma lipoproteins and LCAT activity were studied using a single spin density gradient separation and an exogenous substrate enzyme assay in 41 patients on chronic hemodialysis and in 11 normal subjects. The plasma HDL cholesterol was markedly decreased (33 vs. 63 mg/dl, P < 0.001) while total and LDL-cholesterol were unchanged in the patients. Plasma LCAT activity was significantly lower in the patient group (42 vs. 59 nmoles/4 hr/ml, P < 0.001), but the distribution of activity (studied in 13 dialysis patients and 12 control subjects) was not different between the two groups: 90% being associated with HDL and VHDL lipoprotein fractions. To examine the possible genetic influence on the development of hypertriglyceridemia in the patient group, we examined the ratio of apolipoproteins E3/E2 and CII/CIII in ten of the patients and another group of 13 control subjects. The frequency of heterozygotes for E3 deficiency was not different between the patient (one of ten) and the control (two of 13) groups. While the patient group had lower CII/CIII ratio, the figures did not reach statistical significance. The low LCAT activity in the face of higher plasma triglycerides and low HDL may contribute to impaired lipolysis previously documented in uremic patients. A follow-up study performed 1 year after the initial study confirmed the decreased HDL (51 vs. 71 mg/dl, P < 0.01) and LCAT activity (50 vs. 59 nmoles/hr/ml, P < 0.02) in an exogenous substrate system (N = 20). LCAT measured using the endogenous substrate was not significantly different from the control group (49 vs. 55 nmoles/hr/ml). Changes in LCAT activity induced by a single dialysis were not significant in either assay system.

Lipoprotéines plasmatiques et distribution de la lécithine:cholestérol acyltransférase chez des malades en dialyse. Les lipoprotéines plasmatiques et l'activité LCAT ont été étudiées en utilisant une séparation par centrifugation unique sur gradient de densité et un dosage enzymatique avec un substrat exogène chez 41 malades en hémodialyse chronique et chez 11 sujets normaux. Le cholestérol plasmatique HDL était diminué de façon marquée (33 contre 63 mg/dl, P < 0,001) tandis que les cholestérols total et LDL étaient inchangés chez les malades. L'activité LCAT plasmatique était significativement plus faible dans le groupe des malades (42 contre 59 nmoles/4 hr/ml, P < 0,001), mais la distribution de l'activité (étudiée chez 13 hémodialysés et 12 sujets contrôles) n'était pas différente entre les deux groupes: 90% étaient associés avec les fractions HDL et VHDL des lipoprotéines. Afin d'examiner une possible influence génétique sur le développement d'une hypertrigly-céridémie dans le groupe des malades, nous avons examiné le rapport des apolipoprotéines E3/E2 et CII/CIII chez dix des malades et chez un autre groupe de 13 sujets contrôles. La fréquence des hétérozygotes pour un déficit en E3 n'était pas différente entre les groupes des malades (un des dit) ou des contrôles (deux des 13). Bien que le groupe des malades ait eu un rapport CII/CIII plus faible, les valeurs n'ont pas atteint la signification statistique. La faible activité LCAT en présence de triglycérides plasmatiques plus élevés et de HDL bas pourrait contribuer à l'anomalie de lipolyse préalablement documentée chez les malades urémiques. Une étude évolutive faite un an après l'étude initiale a confirmé la diminution des HDL (51 contre 71 mg/dl, P < 0,01) et de l'activité LCAT (50 contre 59 nmoles/hr/ml, P < 0,02) dans un système utilisant un substrat exogène (N = 20). La LCAT mesurée en utilisant le substrat endogène n'était pas significativement différente du groupe contrôle (49 contre 55 nmoles/hr/ml). Les modifications d'activité LCAT induites par une dialyse unique n'étaient pas significatives dans aucun des systèmes de dosage.

Top

References

  1. Chan MK, Varghese Z, Moorhead JF: Lipid abnormalities in uremia, dialysis and transplantation. Kidney Int 19:625–637, 1981 | PubMed | ISI | ChemPort |
  2. Hueck C-C, Ritz E: Hyperlipoproteinemia in renal insufficiency. Nephron 25:107, 1980
  3. Linder A, Charra B, Sherrard DJ, Scribner BH: Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med 290:697–701, 1974 | PubMed | ISI | ChemPort |
  4. Lowrie EG, Lazarus JM, Mocelin AJ, Bailey GL, Hampers CL, Wilson RE, Merrill JP: Survival of patients undergoing chronic hemodialysis and renal transplantation. N Engl J Med 288:863–867, 1973 | PubMed |
  5. Nestel PJ, Fidge NH, Tan MH: Increased lipoprotein-remnant formation in chronic renal failure. N Engl J Med 307:329–333, 1982 | PubMed | ISI | ChemPort |
  6. Ibels LS, Reardon MF, Nestel PI: Plasma post-heparin lipolytic activity and triglyceride clearance in uremic and hemodialysis patients and renal allograft recipients. J Lab Clin Med 87:648–658, 1976 | PubMed | ISI | ChemPort |
  7. Applebaum-Bowden D, Goldberg AP, Hazzard WR, Sherrard DJ, Brunzell JD, Huttunen JK, Nikkila EA, Ehnholm C: Post-heparin plasma triglyceride lipases in chronic hemodialysis: Evidence for a role for hepatic lipase in lipoprotein metabolism. Metabolism 28:917–924, 1979 | Article | PubMed | ChemPort |
  8. Guarnieri GF, Moracchiello M, Companacci L, Ursini F, Ferri L, Valente M, Gregolin C: Lecithin-cholesterol acyltransferase (LCAT) activity in chronic uremia. Kidney Int 13(suppl 8):S26–S30, 1978
  9. Jung K, Neumann R, Precht K, Nugel E, Scholz D: Lecithin: cholesterol acyltransferase activity, HDL-cholesterol and apolipo-protein A in serum of patients undergoing chronic hemodialysis. Enzyme 25:273–275, 1980
  10. Chan MK, Ramdial L, Varghese Z, Persand JW, Baillod RA, Moorhead JF: Plasma lecithin-cholesterol acyltransferase activities in uremic patients. Clin Chim Acta 119:65–72, 1982
  11. Williams ES, Luft FC: The effect of chronic uremia on fatty acid metabolism in the heart. J Lab Clin Med 92:548–555, 1978
  12. Utterman G, Hees M, Steinmetz A: Polymorphism of apo E and occurrence of dysbetalipoproteinemia in man. Nature 269:604–607, 1977 | Article |
  13. Bories PC, Subbaiah PV, Bagdade JD: LCAT activity in dialyzed and undialyzed chronic uremic patients. Nephron 32:22–27, 1982 | PubMed | ISI | ChemPort |
  14. Lacko AG, Rutenberg HL, Soloff LA: Measurement of the initial rate of serum cholesterol esterification. Biochem Med 7:178–183, 1973
  15. Lipid Research Clinics Program, Manual of Laboratory Operations, Lipid and Lipoprotein Analysis, Washington, D.C., DHEW Publication No. NIH 75-628, U.S. Government Printing Office, vol 1, 1974
  16. Warnick GR, Mayfield C, Albers JJ, Hazzard WR: A gel isoelectric focusing method for specific diagnosis of hyperlipoproteinemia type III. Clin Chem 25:279–284, 1979
  17. Frohlich J, Godolphin WJ, Reeve CE, Evelyn KA: Familial LCAT deficiency. Report of two patients from a Canadian family of Italian and Swedish descent. Scand J Clin Lab Invest 38(suppl 150):156–161, 1978
  18. Fredrickson DS: A physician's guide to hyperlipidemia. Mod Concepts Cardiovasc Dis 41:31, 1972
  19. Chung BH, Wilkinson T, Geer JC, Segrest JP: Preparations and quantitative isolation of plasma lipoproteins: rapid, single discontinuous density gradient ultracentrifugation in a vertical rotor. J Lipid Res 21:184–291, 1980
  20. Chen C-H, Albers JJ: Characterization of proteoliposomes containing apo AI: a new substrate for the measurement of LCAT activity. J Lipid Res 23:680–691, 1982 | PubMed | ISI | ChemPort |
  21. Matz CE, Jonas A: Reaction of human LCAT with synthetic micellar complexes of apo AI, phosphatidylcholine, and cholesterol. J Biol Chem 257:4541–4546, 1982 | PubMed | ChemPort |
  22. Stokke KT, Norum KR: Determination of LCAT in human blood plasma. Scand J Clin Lab Invest 27:21–27, 1981
  23. Bagdade JD, Albers JJ: Plasma HDL concentrations in chronic hemodialysis and renal transplant patients. N Engl J Med 296:1436–1439, 1979
  24. Marcel YL, Vezina C: Lecithimcholesterol acyltransferase of human plasma. J Biol Chem 248:8254–8259, 1973
  25. Rose HG, Juliano J: Regulation of plasma lecithin-cholesterol acyltransferase in man. I. Increased activity in primary hypertriglyceridemia. J Lab Clin Med 88:29–43, 1976
  26. Staprans I, Felts JM, Zacherle B: Apoprotein composition of plasma lipoproteins in uremic patients on hemodialysis. Clin Chim Acta 93:135–143, 1979
  27. Frohlich J, Hon K, McLeod R: Detection of heterozygotes for familial LCAT deficiency. Am J Hum Genet 34:65–72, 1982
  28. Albers JJ, Chen C-H, Adolphson JL: LCAT mass: its relationship to LCAT activity and cholesterol esterification rate. J Lip Res 22:1206–1213, 1982
  29. Chen C-H, Albers JJ: Distribution of LCAT in human plasma lipoprotein fractions. Evidence for the association of active LCAT with LDL. Biochem Biophys Res Comm 107:1091–1096, 1982
  30. Nordby G, Berg T, Nilkson M, Norum KR: Secretion of LCAT from isolated rat hepatocytes. Biochem Biophys Acta 450:69–77, 1976
  31. Fielding PE, Fielding CJ: A cholesteryl ester transfer complex in human plasma. Proc Natl Acad Sci (USA) 77:3327–3330, 1980
  32. Holdsworth G, Stocks J, Dodson P, Galton DJ: An abnormal triglyceride-rich lipoprotein containing excess sialylated apo CIII. J Clin Invest 69:932–939, 1982

Extra navigation

.
ADVERTISEMENT