Low–Density Lipoprotein Adsorption for Arteriosclerotic Patients

Abstract: A wide variety of treatments is now available for arteriosclerosis obliterans (ASO) patients, not very successful in some cases. Low—density lipoprotein (LDL) apheresis using an extracorporeal adsorption column containing dextran sulfate cellulose beads was applied to control lipid levels intensively in ASO patients with accompanying drug—resistant hyperlipidemia. A series of the apheresis procedures had a remarkable impact on clinical symptoms and physiological findings with improvement in intermittent claudication observed in more than 80% of the patients. Improvements in plethysmogram and thermogram readings suggested an increased circulation in lower extremities in more than 80% of patients. In addition, the treatment improved blood rheology, as evidenced by a reduction in blood viscosity. In a follow—up study made by sending a questionnaire to previously treated patients, it was revealed that improvements in clinical symptoms were well maintained even after cessation of the treatment. In conclusion, LDL apheresis proved to be a useful therapeutic tool in ASO patients having elevated lipid levels     

Low–Density Lipoprotein Apheresis in the Treatment of Two Patients with Coronary Heart Disease and Extremely Elevated Lipoprotein (a) Levels

Abstract: Hyperlipidemia and elevated lipoprotein (a) (Lp[a]) levels have been linked to the development and progression of premature atherosclerosis. Our study concerned 2 white male patients (aged 36 and 42 years) with heterozygous familial hypercholesterolemia and extremely elevated Lp(a) concentrations that were resistant to diet regimens and lipid–lowering drugs. The patients were treated with low–density lipoprotein (LDL) apheresis for 59 months (Liposorber system, Kaneka, Japan) and 19 months (immunoadsorption system, special Lp(a) columns; Lipopak; Pocard, Russia), respectively. The concentration of Lp(a) decreased on average by 50%, total cholesterol by 27%, LDL cholesterol by 41%, triglycerides by 43%, and fibrinogen by 16%. High–density lipoprotein (HDL) cholesterol increased by approximately 4%. Before treatment with LDL apheresis, each patient had suffered 3 myocardial infarctions, and had had 4 and 6 coronary angiographies with 2 and 4 percutaneous transluminal angioplasties (PTCAs), respectively. Since treatment with LDL apheresis, no myocardial infarctions or cardiac complaints were observed. In the course of treatment, both patients reported an increased performance. Available data suggest that LDL apheresis may be effective in the treatment of patients, the only risk factor for premature atherosclerosis being extremely elevated Lp(a) concentrations.     

Short–and Long–Term Effects on Serum Lipoproteins by Three Different Techniques of Apheresis

Abstract: Low–density lipoprotein (LDL) apheresis is applied in patients with coronary heart disease because of severe inherited forms of hypercholesterolemia, for which dietary and combined drug treatment cannot lower LDL cholesterol concentrations less than 130 mg/dl. The following article describes the changes in lipoprotein levels in a total of 19 patients undergoing weekly LDL apheresis. Immunoadsorption, operating with polyclonal antibodies against apolipoprotein B–100, was used in 6 patients. Five patients were put on heparin–induced extracorporeal LDL precipitation (HELP) therapy; 6 received dextran sulfate adsorption treatments. Under steady–state conditions a single treatment reduced LDL cholesterol by 149 ± 3 m/dl with immunoadsorption, 122 ± 2 mg/dl with HELP, and 124 ± 18 mg/dl with dextran sulfate adsorption. Lipoprotein (a) (Lp[a]) declined by 52 to 65%. Very low density lipoprotein (VLDL) cholesterol and VLDL triglycerides declined by 45 to 55% because of the activation of lipoprotein lipase and precipitation during the HELP procedure. In all procedures, there was a small reduction in the different high–density lipoprotein fractions, which had returned to normal after 24 h. The long–term HDL3 cholesterol levels increased significantly. During all procedures there was a decrease in the molar esterification rate of lecithin cholesterol acyltrans–ferase activity. All changes in lipid fractions were paralleled by changes in the corresponding apolipoprotein levels. It is concluded that all three techniques described are powerful tools capable of lowering LDL cholesterol in severe hereditary forms of hypercholesterolemia. In HELP and dextran sulfate adsorption, the amount of plasma is limited by the elimination of other plasma constituents. Immunoadsorption may thus be preferred in very severe forms of hypercholesterolemia.     

Extracorporeal Removal of Lipids by Dextran Sulfate Cellulose Adsorption

Abstract: Extracorporeal removal of low–density lipoprotein (LDL) cholesterol by dextran sulfate adsorption is indicated in patients with diet and drug resistant hypercholesterolemia to prevent or to regress coronary heart disease. Plasma separation is the first step in the process, followed by adsorption of LDL cholesterol and lipoprotein (a) (Lp[aJ) to negatively charged dextran sulfate co–valently bound to cellulose beads. The reduction per treatment in LDL cholesterol is 65–75% and in Lp(a) 40–60%. In most patients one treatment per week is sufficient to reduce mean LDL to 100–150 mg/dl. Minor side effects occur in 2–6% of treatments. Major side effects are rare. In uncontrolled studies long–term treatment was associated with inhibition of progression and induction of regression of coronary artery disease. LDL apheresis by dextran sulfate may increase blood perfusion of some tissues, and preliminary results indicate a beneficial effect on therapy resistant nephrotic syndrome with hypercholesterolemia.     

Treatment of Homozygous Familial Hypercholesterolemia with Low Density Lipoprotein Apheresis: A 4 Year Follow-Up Study

Abstract: Hypercholesterolemia and elevated lipoprotein (a) (Lp[a]) levels are considered to be risk factors for the development and progression of premature atherosclerosis. The purpose of our report is to describe the effects of low density lipoprotein (LDL) apheresis (Liposorber system, Kanegafuchi Chemical Industrial Company LTD, Osaka, Japan) on serum lipoprotein concentrations and the clinical status in 2 male patients with homozygous familial hypercholesterolemia. Compared with pretreatment values, the posttreatment concentrations of total cholesterol, LDL cholesterol, and Lp(a) were significantly reduced by 50–60% (p < 0.0001). The concentration of high density lipoprotein (HDL) cholesterol was slightly affected. After one treatment session, LDL cholesterol and Lp(a) were decreased on average by 65% and then increased to reach about 70–75% of the pretreatment values before the next session. Prior to the treatment with LDL apheresis, each patient had suffered one myocardial infarction and had had 2 coronary angiographies. After treatment with LDL apheresis, neither cardiac complaints nor myocardial infarction were observed. The xanthomas were much decreased during the treatment or disappeared. We conclude that LDL apheresis can be continued safely and without major technical problems for several years. Apheresis effectively lowers the serum levels of total and LDL cholesterol. Furthermore, it reduces Lp(a), which is not influenced by lipid-lowering drugs. The reduction of LDL cholesterol and Lp(a) may delay the progression of the atherosclerotic process, thereby helping to reduce the risk of new episodes of coronary heart disease and thus extending the life expectancy in these patients.     

Treatment of Severe Hyperlipidemia: Six Years' Experience with Low–Density Lipoprotein Apheresis

Abstract: In total, 30 patients suffering from familial hypercholesterolemia, resistant to diet and lipid–lowering drugs, were treated for up to 6 years (3.6 ± 1.6; range, 0.2–6.8 years) with low–density lipoprotein (LDL) apheresis. Three different systems were used; the dextran sulfate adsorption system (Kaneka) for 27 of 30 patients, the immunoadsorption system from Baxter for 2 of 30 patients, and the immunoadsorption system with special li–poprotein(a) (Lp[a]) columns from Lipopak for one patient. Prior to the LDL apheresis, 23 of 30 patients suffered from coronary heart disease. Twenty of 23 patients suffered intermittently from symptoms of angina, excertional dyspnea, and claudication. With LDL apheresis, reductions of 47% for total cholesterol, 49% for LDL, 26% for Lp(a), and 40% for triglycerides were reached. Severe side effects such as shock or allergic reactions were very rare (0.55%). In the course of treatment with LDL apheresis, an improvement in general well–being and increased performance were experienced in 27 of 30 patients. A reduction of nitrate medication between 60 and 100% was observed in 17 of 23 patients. The present data clearly demonstrate that treatment with LDL apheresis in patients suffering from severe familial hyperlipidemia, resistant to maximum conservative therapy, is very effective and safe even over long periods of time.     

Low–Density Lipoprotein Removal Methods by Membranes and Future Perspectives

Abstract: Since the application by Thompson et al. in 1975 of plasma exchange for the treatment of 2 patients with familial hyperlipidemia, plasma purification techniques for selective low–density lipoprotein (LDL) removal (i.e., LDL apheresis) have been developed and adopted for the management of this disease. Thermofil–tration is one of the LDL apheresis systems that utilizes membrane techniques developed by Nose and Malchesky's group in 1985. This article reviews its rationale, in vitro studies, animal studies, and clinical investigation. Thermofiltration effectively and selectively removes LDL cholesterol while retaining in the plasma physiologically important macromolecules such as albumin and high–density lipoprotein (HDL) cholesterol. Based on the global view of the treatment of atherosclerosis by LDL apheresis, membrane techniques are as effective, safe, and simpler to apply than other methods. Additionally, these methods are effective for the removal of lipoprotein (a) and fibrinogen; thus, they can address the needs in these application areas.     

Low–Density Lipoprotein Apheresis Versus Lipid Lowering Drugs in the Treatment of Severe Hypercholesterolemia: Four Years' Experience

Abstract: Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Li–popak; 24 patients, aged 50.2 ±11.5 years), diet, and/or lipid–lowering drugs or with diet and lipid–lowering drugs only (23 patients, aged 48.8 ±11.8 years). After treatment periods of 49.8 ±13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 ± 15.1 months (drug group), the ensuing results revealed significant differences (p <0.0001): –47.3% versus –12.1% for total cholesterol, –46.9% versus –21.8% for LDL, +8.4% versus +0.9% for HDL, –52.0% versus – 13.1% for the LDL/HDL ratio, –36.4% versus –16.2% for triglycerides, and –25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia.     

Low–Density Lipoprotein Hemoperfusion Using a Modified Polyacrylate Adsorber: In Vitro, Ex Vivo, and First Clinical Results

Abstract: Current lipid apheresis techniques can remove low–density lipoprotein (LDL) cholesterol only from plasma, i.e., a primary cell–plasma separation step is mandatory. This article describes in vitro, ex vivo, and clinical results using a new LDL adsorber compatible with human whole blood. It consists of modified polyacrylate, the negative charges of which can interact with the positively charged protein B moiety of LDL, thus retaining these particles on the surface of the adsorber. After the efficacy and selectivity of LDL removal had been demonstrated in vitro and ex vivo, a clinical pilot study corroborated these results. Thus, treating 60 ml of blood per kilogram of body weight in a single session, LDL hemoperfusion reduced LDL cholesterol by 50%, lipoprotein (a) by 17%, and triglycerides by 19% in 6 hy–percholesterolemic patients. High–density lipoprotein cholesterol recovery amounted to 97%. In conclusion, LDL hemoperfusion holds great promise for the future.     

Assessment of Currently Available Low-Density Lipoprotein Apheresis Systems

Abstract: It has already been 10 years since the introduction of low-density lipoprotein (LDL) apheresis technologies. They have been established as technically and medically feasible for long-term treatment and economically acceptable, and their long-term treatment effects have been determined. Currently, there are efforts to develop more selective LDL removal systems. However, after 10 years of research, it is time to carefully review this strategy. The approach may have become too specific in light of the multiple macromolecules involved in the pathogenesis of atherosclerosis. In this paper, the six currently available LDL apheresis systems (plasma exchange, double filtration plasmapheresis, thermofiltration, LDL chemical adsorption (Kaneka system), LDL immunoadsorption, and the heparin-induced extracorporeal LDL precipitation [HELP] system) were reviewed and scored from various points of view such as effectiveness, simplicity, safety, and cost performance. Finally, each system was assessed from the global point of view in relation to the pathogenesis of lipid-related diseases.     

Prevention of Restenosis after Coronary Angioplasty with Low-Density Lipoprotein Apheresis

Abstract: A prospective study was performed to determine whether low-density lipoprotein (LDL) apheresis, when performed only immediately before and after percutaneous transluminal coronary angioplasty (PTCA), is effective in preventing restenosis of coronary artery lesions following PTCA. Thirty-six patients with coronary heart disease (CHD) and hypercholesterolemia were divided into 2 groups. The 9 patients in the LDL group underwent LDL-apheresis 1 day before and 5 days after PTCA while the 27 patients of the control group underwent PTCA but did not undergo LDL-apheresis. Follow-up coronary angiography (CAG) was performed 4 months after PTCA. The rate of restenosis of coronary artery lesions was significantly lower in the LDL group (0%) than in the control group (30%). These findings suggest that LDL-apheresis, when performed before and after PTCA, is effective in preventing restenosis of coronary artery lesions in patients with CHD and hypercholesterolemia.     

Lipoprotein(a) Apheresis in Severe Coronary Heart Disease: an Immunoadsorption Method

Lipoprotein(a) (Lp[a]) is associated with an increased cardiovascular risk. It is similar to low-density lipoprotein with an additional molecule of apo A covalently linked to apo B-100 by one disulfide bridge. Apo A is highly homologous to plasminogen. The kringle 4 motive of plasminogen is repeated between 10 and 40 times in apo (a). Currently, there is no drug therapy available to lower Lp(a). Since October 1993, we have carried out over 160 immunoadsorption treatments on 3 patients with elevated Lp(a) as their only risk factor and a history of myocardial infarction. Lp(a) was removed from plasma by sepharose coupled anti-Lp(a) columns. Lp(a) levels were lowered from above 170 mg/dl to below 30 mg/dl immediately after Lp(a) apheresis. To achieve this, the patient's plasma volume had to be treated 2 to 3 times. Nonspecific protein loss during column changes remained negligible. There were no serious unwanted effects during or after treatment. Minor circulatory problems (tachycardia, flush) occurred in 11% of the treatments but only with plasma flow rates above 55 ml/min. In 1 patient, coronary angiography after 2 years and in another patient after 1 year showed no progression. The third patient has not yet had repeat coronary angiography. Like the others, he reported subjective improvement after 1 year of apheresis. It is concluded that Lp(a) apheresis may retard progression of atherosclerosis in patients with selective Lp(a) elevation. Further studies to support this hypothesis are needed.     

Bone Mineral Density Distribution Curves in Spanish Adults With Down Syndrome

According to reports from small-sized case series, adults with Down syndrome (DS) appear to have lower bone mineral density (BMD) than the general population. The objective of our study was to further characterize the bone mass acquisition curve in an adult DS population. This is a retrospective study of 297 adults with DS from the Adult Down Syndrome Outpatient Clinic of a tertiary care hospital in Madrid, Spain, who underwent a bone densitometry (Hologic QDR-4500W), for clinical purposes between January 2010 and June 2015. The mean age of our sample population was 34?yr (±10.9); 51% were women. Bone mass peak was reached earlier and was lower than the general population (around 20–25?yr), with almost parallel curves. The mean BMD was 0.715?±?0.12?g/cm² in femoral neck (FN) and 0.872?±?0.11?g/cm² in lumbar spine (LS). According to FN scores, 52% of the subjects were classified as osteopenic and 18% as osteoporotic. According to LS scores, frequencies were 54% and 25%, respectively. BMD was considered inadequate for the age (Z-score?<??2 standard deviation) in 18% of the subjects at FN and 40% at LS. BMD at LS was significantly lower in males than in females (52% vs 38%, p?<?0.001). Male DS subjects had a 2.58-fold (95% confidence interval: 1.57–4.25) higher risk of developing reduced BMD at LS than females. Persons with DS reach the bone mass peak earlier and this bone mass is lower than the general population. Among subjects with DS, male gender is a risk factor for developing low BMD, especially at LS.     

Lipoprotein A Levels after Intestinal Bypass Operation for Morbid Obesity

Background: Serum Lipoprotein A [Lp(a)] is considered an independent risk factor for cardiovascular disease. Reduction of other risk factors such as serum triglycerides and serum cholesterol is seen after weight reduction but it has been difficult to demonstrate a similar reduction of Lp(a). In this study Lp(a) is studied following weight reduction after intestinal bypass surgery for obesity. Methods: A cross-sectional study was performed in which Lp(a) levels were compared between patients operated with intestinal bypass surgery for obesity (bilio-intestinal bypass) and a closely matched control group. The controls were chosen so as to correspond to the operated patients' preoperative body mass indices. Results: The operated group had reduced their body mass index from a mean of 42 kg/m² to a mean of 29 kg/m² and had a significantly lower mean serum Lp(a) level (113 mg/l, SEM 34) than controls (207 mg/l, SEM 37), p < 0.05. Conclusion: Lowered Lp(a) levels are correlated to substantial weight loss following intestinal bypass surgery for obesity.     

HELP Apheresis in the Treatment of Sepsis

Heparin induced extracorporeal lipoprotein fibrinogen precipitation (HELP) is an established procedure for removal of low-density lipoprotein (LDL) cholesterol, lipoprotein (a), and fibrinogen in patients with severe hypercholesterolemia. In vitro studies revealed that HELP also removes endotoxin, tumor necrosis factor α (TNF-α) and C-reactive protein (CRP). With the intention to treat, we applied this procedure to 4 patients with severe gram-negative sepsis with highly elevated endotoxin blood levels. Nine treatments were performed, 6 using the standard HELP precipitating buffer and 3 without addition of heparin to the precipitating buffer. Heparin was omitted from the precipitating buffer to avoid fibrinogen depletion in patients at risk (low fibrinogen, postoperative). The average processed plasma volume was 3,386 ml in the standard and 2,963 ml in the modified treatment. Mean reductions (%) in plasma solute concentrations were (standard/modified procedure) as follows: endotoxin, 50/57; TNF-α, 25/5; CRP, 49/55; fibrinogen, 49/6; total cholesterol, 38/5; and apolipoprotein B (Apo B), 41/2. Both treatment modalities were equally effective in removing endotoxin and CRP. With the modified precipitation buffer, fibrinogen was not removed. To further simplify the extracorporeal treatment, we have designed a closed-loop circuit with 2 adsorbers in series, one for removal of TNF-α (dextran sulfate modified cellulose) and the other for removal of endotoxin (DEAE-cellulose). In vitro evaluation confirmed very efficient endotoxin and TNF-α removal from plasma. This system is very simple, operates at physiological pH, and uses adsorbers already in clinical use for other purposes.     

Smaller low-density lipoprotein size as a possible risk factor for the prevalence of coronary artery diseases in haemodialysis patients: associations of cholesteryl ester transfer protein and the hepatic lipase gene polymorphism with low-density lipoprotein size

Aim: Smaller low‐density lipoprotein (LDL) size has recently been reported as a non‐traditional lipid risk factor for coronary artery disease (CAD). Cholesteryl ester transfer protein (CETP) and the C/T hepatic lipase (HL) gene polymorphism may promote LDL size reduction via the CETP‐mediated exchange of CE for triglyceride (TG) and subsequent HL‐mediated TG hydrolysis in LDL. However, little is known about LDL size status and its relationship with CAD prevalence in haemodialysis (HD) patients who are at high risk for atherosclerosis. Methods: CETP levels, HL genotypes and LDL size were determined, and the determinants of LDL size and its association with CAD prevalence in HD patients (n = 236) aged over 30 years were investigated. Results: The HD patients had a similar LDL size to the healthy subjects. In the HD group, high‐density lipoprotein cholesterol was an independent positive determinant of LDL size, while log₁₀ (TG) was an independent negative determinant in the high (≥2.1 µg/mL) but not low (<2.1 µg/mL) CETP group. In the patients with hypertriglyceridemia, the high CETP group had a significantly smaller LDL size than the low CETP group. Among the patients with above‐median TG levels, the CC genotype and CETP were independent negative determinants of LDL size. In the whole group and the high CETP group, the patients with CAD had a significantly smaller LDL size than those without CAD. Finally, DM and smaller LDL size were identified as independent risk factors for CAD prevalence. Conclusion: These suggest that a smaller LDL size, which is associated with higher levels of TG and CETP and the HL/CC genotype, may serve as a risk factor for CAD in HD patients.     

Development of Selective Low-Density Lipoprotein (LDL) Apheresis System: Immobilized Polyanion as LDL-Specific Adsorption for LDL Apheresis System

Abstract: Low-density lipoprotein (LDL) is widely recognized as one of the major risk factors for developing coronary heart diseases. Despite intensive development of LDL-lowering drugs, there still exist those patients with refractory hyperlipidemia whose plasma LDL levels are not sufficiently lowered by drugs. LDL apheresis, direct removal of plasma LDL from circulating blood, is thought to be the most promising treatment for such refractory patients. Various techniques, such as the use of an im-munoadsorbent utilizing an anti-LDL antibody, have been used in an attempt to achieve the selective removal of LDL. However, none were widely used because of complications, poor selectivity, and so forth. To establish a safe and effective LDL apheresis system, we chose a synthetic affinity adsorbent as the LDL-removing device. Synthetic polyanion compounds were used as the affinity ligands for LDL adsorbent to simulate the anion-rich sequence of LDL binding sites in the human LDL receptor. Among various polyanion compounds, those polyanions with sulfate or sulfonate groups and hydrophilic backbone were found to have strong affinity for LDL. In contrast, polyanions with carboxyl groups showed poor affinity. Dextran sulfate (DS) was selected as the affinity ligand of LDL adsorbent for its high affinity and low toxicity. The influence of its charge density and molecular weight on its affinity for LDL was suitable. The affinity rapidly increased as the charge density increased, then, reached a constant value. Little affinity was found for either the DS monomer (glucose sulfate) or DS with a molecular weight higher than 10⁴ daltons whereas DS with molecular weights in the midrange showed strong affinity. DS with a midrange molecular weight was immobilized on cellulose hard gel to give LDL adsorbent clinical application. The adsorbent demonstrated an excellent selectivity for LDL and very low density lipoprotein (VLDL) in vitro. Adsorption of high-density lipoprotein and major plasma proteins was almost negligible. Additional study of the LDL-binding mechanism revealed that DS directly interacts with positively charged sites on LDL, which demonstrates that the nature of the interaction is the same as that of LDL receptor. An LDL adsorption column (Liposorber) packed with an LDL adsorbent and polysulfone hollow-fiber plasma separator (Sulflux) was developed as an efficient LDL apheresis system. Clinical investigation proved that this system is capable of intensively lowering the plasma LDL level without affecting major plasma components.     

Lipoprotein(a) in patients with proteinuria.

Lipoprotein(a) (Lp(a)) has recently been recognized to be a risk factor for coronary heart disease. Lp(a) median values in the absence of renal disease are around 10 mg/dl. Higher levels (greater than or equal to 30 mg/dl) correlate with the occurrence of coronary heart disease, particularly in the presence of elevated cholesterol. We have studied Lp(a) in 76 adults with proteinuria. Fifty had glomerular diseases and 26 non-glomerular diseases, with renal function varying from normal to advanced chronic renal failure. Lp(a) values were shifted to the right, with a median of 21.0 mg/dl, and 25% of patients had values of 30 mg/dl or more. Lp(a) did not correlate with cholesterol, age, lipoprotein subclasses, apoproteins A-I or B-100, albumin, creatinine, or creatinine clearance. Median Lp(a) values did not differ significantly comparing men versus women, or glomerular versus non-glomerular disease. Lp(a) may inhibit fibrinolysis, and is deposited in atherosclerotic lesions. Although the cause of these elevated Lp(a) levels is uncertain, we propose that they contribute to the increased risk of coronary heart disease in the nephrotic syndrome, and may play a role in progressive renal disease.     

Long-term efficiency, biocompatibility, and clinical safety of combined simultaneous LDL-apheresis and haemodialysis in patients with hypercholesterolaemia and end-stage renal failure

Three hypercholesterolaemic patients on maintenance haemodialysiswith angiographically proven coronary artery disease were treatedin a once-a-week schedule by combined, synchronous lipid apheresis(using heparin-induced extracorporeal LDL precipitation) andhaemodialysis (HELP/HD) for 65–104 weeks. Clinical side-effectswere few and mostly related to high ultrafiltration rates inpatients with low compliance regarding interdialytic fluid restriction.Biocompatibility of the procedure was shown to be good and bloodcell losses, leukocyte (elastase release) and thrombocyte (ß-thromboglobulinextrusion) as well as complement (C3a formation) activationwere minimal. Interestingly, most of the C3a generated in theextracorporeal HELP circuit was immediately removed again inthe precipitate filter. In the pseudo-steady-state after 3 monthsof regular therapy, acute haematocrit-corrected reduction ofplasma components after the session compared to pre values wereabout 55% for the risk factors LDL cholesterol (LDL-C), lipoprotein(a)(Lp(a)), and fibrinogen (FIB) with good recovery of HDL-C andother proteins. Urea, creatinine, and phosphate eliminationwas similar to normal haemodialysis. Mean interapheresis values of risk factors after one (n=2) andtwo (n=1) years of treatment were crucially dependent upon ultrafiltration(UF); thus, in two patients with high UF LDL-C concentrationsamounting to 185 and 220mg/dl at baseline and were reduced toabout 135mg/dl LDL-C, while in the patient with low UF the reductionwas from 231 mg/dl to 80 mg/dl. The atherogenic index (LDL-C/HDL-C)was reduced from 6.4 and 5.1 to about 4.3 in patients with highUF, from 6.1 to 3.3 in the patient with low UF. Fibrinogen andLp(a) were normalized in all patients. In summary, the combined HELP/HD treatment in hypercholesterolaemicdialysis patients proved to be a safe, effective, and selectiveprocedure for lipoprotein and fibrinogen normalization withexcellent biocompatibility and good clinical patient tolerance,providing a tool ready for future atherosclerosis regressionstudies in ESRD patients.     

Serum Amyloid A and P Protein Levels are Lowered by Dextran Sulfate Cellulose Low-Density Lipoprotein Apheresis

The present study describes the short-term effect of dextran sulfate cellulose (DSC) low-density lipoprotein (LDL) apheresis using a plasma separator equipped with a polysulfone (PS) membrane filter (PS/DSC-LDL apheresis) on the serum amyloid A (SAA) and P (SAP) protein levels during treatment in a patient with familial hypercholesterolemia (type IIa, heterozygote). PS/DSC-LDL apheresis markedly lowered both the SAA (reduction percentage, 84.1 ± 8.2%) and SAP (91.4 ± 5%) levels, which returned to their respective initial levels within 4 days. Experimentally, the levels of both proteins also decreased on passage through the DSC minicolumn without a PS membrane, indicating that the DSC resin had an affinity to both proteins. These results suggest that PS/DSC-LDL apheresis may be advantageous for amyloid protein accumulating disorders, including amyloidosis and atherosclerosis.