Nephrol Dial Transplant (2000) 15: 738-740
© 2000 European Renal Association-European Dialysis and Transplant Association
Letters
Long-term efficacy of lipoprotein apheresis in homozygous familial hypercholesterolaemia
1 Service de Néphrologie, Hôpital Tenon, Paris, France 2 Division of Nephrology, Department of Medicine, Hôpital de Sion, Switzerland
Sir,
Homozygous familial hypercholesterolaemia (FH) has an aggressive course with poor prognosis and its conventional treatment (dietary regimen and lipid-lowering drugs) remains ineffective. Extracorporeal low-density lipoprotein (LDL) removal is indicated in patients with FH to prevent or to regress coronary heart disease (CHD) [1]. To reduce LDL in these patients, several methods of extracorporeal LDL removal have been introduced. We focused the present report on the long-term lipoprotein changes of three procedures; (i) plasma-exchange (PE), (ii) double filtration plasmapheresis (DFPP), and (iii) dextran sulfate cellulose adsorption (DSCA) in a patient suffering from homozygous FH associated to severe CHD.
Case.
A 30-year-old white man with homozygous FH had undergone a double saphenous-vein coronary-artery bypass graft at the age of 11 years because of grade III angina and severe coronaropathy. At this time, physical examination revealed multiple xanthomas spread over the body as well as bilateral gerontoxons. The results of serum lipid and lipoprotein profile performed from 1983 to 1999 are shown in Table 1
. From 1983 to 1989, unselected PE (1983–1987) and DFPP (1987–1989) were used when the DSCA system, a more selective LDL apheresis method, was introduced. This technique is still maintained in 2000 (once a week). Present medication associates a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (atorvastatin), an antioxidant (
-tocopherol), an angiotensin II receptor-1 antagonist (irbesartan) and aspirin. Clinical evaluation shows complete regression of the xanthomas and no recurrence of angina. The family history reveals heterozygous HF phenotype without any symptom of CHD in the father, the mother and two brothers. One of the patient's brothers was homozygous and died from a myocardial infarction when he was 13 years old.
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Comment.
Familial hypercholesterolaemia is an inherited disease with an incidence of one per 1000 000 population for the homozygote type. Total plasma cholesterol levels as well as LDL concentration of these patients are usually very high, and CHD represents the most frequent complication of FH [2]. Since the drugs currently used in the management of hypercholesterolaemia, such as resins or classical HMG-CoA reductase inhibitors, induce an overexpression of LDL receptor, which are severely reduced or absent in homozygous FH, pharmacological treatment of these patients is usually not effective in the reduction of plasma cholesterol levels [3]. However apheresis techniques as used in our patient are capable, although to different extents, to lower LDL by 50, 68 and 74% as well as total cholesterol by 48, 58, and 72% for standard PE, DFPP and DSCA respectively [4]. ApoB, the major protein constituent of LDL, is involved in this particle removal by all LDL apheresis techniques, especially in DSCA (negatively charged). This last lipoprotein, found to be associated with CHD [5], is genetically determined and is not likely to be modified by environmental or pharmacological factors. Familial hypercholesterolaemia seems to be associated with increased levels of Lp(a) and might represent a further risk factor in these patients. Thus, the LDL-receptor defect has a dual effect on CHD morbidity by increasing both LDL and Lp(a) concentrations. It is of great clinical importance to note that LDL apheresis methods eliminate with high efficacy other plasma proteins of atherogenic potency such as fibrinogen. The aggressive lipid lowering with LDL apheresis may improve endothelial function by inducing changes in coronary tone. Due to technical and material reasons, unselective PE and DFPP are usually associated with decreased concentrations in total HDL values as observed in this case (-38% and -25% (0.8±0.1 vs 0.6±0.1; 
1983–1989) respectively). In contrast HDL concentrations increase with DSCA, by an average of 38% in this case, for electrical charge and molecular weight reasons.
In conclusion, LDL apheresis is effective and safe in the treatment of FH. In addition, the long-term follow-up reveals that symptoms are well maintained even after 16 years. All three types of apheresis techniques are powerful tools for lowering LDL, but to different extents. It appears that DSCA-LDL apheresis is more selective and appropriate than unselective PE and DFPP for the treatment of FH.
References
- Goldstein JL, Brown MS. Familial hypercholesterolemia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds The Metabolic Basis of Inherited Disease. McGraw-Hill, New York: 1989: 672–712
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Brown NS, Goldstein JL. A receptor mediated pathway for cholesterol homeostasis. Science1986; 232: 34–47
[Free Full Text] - Uany R, Vega GL, Grundy SM, Bilheimer DW. Lovastatin therapy in receptor-negative homozygous familial hypercholesterolemia: lack of effect on low-density lipoprotein concentration or turnover. J Pediatr1988; 113: 383–392
- Thompson GR, Lowenthal R, Myant NB. Plasma exchange in the management of homozygous familial hypercholesterolemia. Lancet1975; 1: 1208–1211[Medline]
- Seed M, Hoppicler F, Reaveley D, McCarthy SRN, Thompson GR, Boerwinkle E, Utermann G. Relation of serum lipoprotein (a) concentration and lipoprotein (a) phenotype to coronary heart disease in patients with familial hypercholesterolemia. N Engl J Med1990; 322: 1494–1499[Abstract]
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