LDL-apheresis Research Articles

Homozygous familial hypercholesterolemia in Spain. Data from Registry of the Spanish Atherosclerosis Society.

Abstract Homozygous familial hypercholesterolemia (HoFH) is a rare disease characterized by the presence of two pathogenic variants in the LDLR, APOB, PCSK9 or LDLRAP1 genes, which cause very high levels of LDL cholesterol and premature atherosclerotic cardiovascular disease (ASCVD). The objective of this study is to analyze the current situation regarding diagnosis, cardiovascular disease, lipid-lowering treatment and degree of control of lipids in patients with HoFH in the National Dyslipidemia Registry of the Spanish Atherosclerosis Society. Methods Subjects with HoFH, confirmed by the presence of two pathogenic variants in the genes mentioned above, included in the registry from 2013 to June 2023 with an updated review were analyzed. Results 71 HoFH subjects were included. 40.8% were women, aged 52 [24-62] years, 57 adults and 13 children. The median follow-up was 7 [4-13] years. Age of diagnosis was 14 [2-26] years, with 10% of ASCVD at diagnosis and 27% of current ASCVD at 40.6 (13.4) years of age. 38% were on PCSK9i, 9 patients on lomitapide, 9 on LDL apheresis and 1 patient on evinacumab. Subjects with more than 4 therapies achieved >80% reduction in LDLc. In the last visit, the median LDLc was 139.3 [89.4-204.2] mg/dL. ASCVD was strongly associated with male sex and family history of ASCVD, relative risk 5.26 (1.53-18.10) and 2.53 (1.03-6.26), p<0.05, respectively. Only 18% and 10% meet the recommended LDLc goal in primary and secondary prevention respectively. Conclusions The current situation of HoFH in Spain is better than expected, with marked reductions in LDLc levels with new treatments. In this population, recommended LDLc goals are difficult to achieve despite maximum lipid-lowering therapy. ASCVD has been reduced and delayed by two decades.

Targeted NGS Revealed Pathogenic Mutation in a 13-Year-Old Patient with Homozygous Familial Hypercholesterolemia: A Case Report

Familial hypercholesterolemia is an autosomal hereditary disease defined by an increased level of low-density lipoprotein cholesterol (LDL-C), which predisposes significant risks for premature cardiovascular disorders. We present a family trio study: proband, a 13-year-old Kazakh girl with homozygous familial hypercholesterolemia (HoFH) and her parents. HoFH is much more rare and severe than a heterozygous form of the disorder. HoFH patients generally present with LDL-C levels exceeding 13 mmol/L, resulting in early and life-threatening cardiovascular events within the first decades of life. In cases of neglected treatment, young patients have a risk of death from coronary diseases before the age of 30. The aim of this research was to identify genetic mutations in the affected patient and her parents. Genetic testing was necessary due to highly elevated LDL-C levels and the presence of multiple xanthomas. Targeted next-generation sequencing (NGS) was performed in this study using the Illumina TruSight cardio panel, which targets 174 genes related to cardiac disorders. The girl was diagnosed with HoFH based on the results of genetic testing. A biallelic mutation was observed in exon 3 of the low-density lipoprotein receptor (LDLR): c. 295 G>A (p.Glu99Lys). Sanger sequencing confirmed that the mutant gene was inherited from both parents. After confirming the genetic diagnosis of HoFH, the patient was treated with LDL apheresis and statins. This case report is the first study of HoFH in a pediatric patient from the Central Asian region. Globally, it emphasizes the need for increased clinical awareness among healthcare providers, as early detection and intervention are important for improving outcomes, particularly in pediatric patients with this rare genetic disorder.

Unveiling homozygous familial hypercholesterolemia in Greece: a comprehensive analysis of baseline traits and LDL goal achievement in adults from the HELLAS-FH Registry

Abstract Background Homozygous familial hypercholesterolemia (HoFH) is a severe genetic disorder characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) levels. This study aimed to analyze demographic characteristics, lipid profile, and rate in achieving LDL-C targets in adult HoFH patients in Greece. Methods This is a cross-sectional analysis of the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH). Adults with genetically or clinically diagnosed HoFH were included. Median LDL-C levels were assessed during HoFH diagnosis and enrollment. Results Seventeen HoFH adults (mean age 41 years and mean age at diagnosis 31 years, men 58.8%). Genetic confirmation of HoFH was available in 10 patients, while the remaining were diagnosed based on clinical criteria. Family history of atherosclerotic cardiovascular disease was documented in 70.5% of patients. Clinical presentations varied, with 47.0% exhibiting tendon xanthomas, 17.6% xanthelasmas, 23.5% corneal arcus, and 52.9% premature coronary artery disease (CAD). Predominant treatment involved statins (88.2%), ezetimibe (58.8%),PCSK9i (23.5%), lomitapide (29.4%), while LDL apheresis was utilized in 23.5%. Median LDL-C levels were 407 mg/dL (10.53 mmol/L) at diagnosis and 226 mg/dL (5.84 mmol/L) at enrollment. None of the patients achieved the LDL-C target set by the 2019 EAS/ESC Guidelines. Conclusion The challenges of delayed diagnosis, undertreatment, and unattained LDL-C targets persist in HoFH management in Greece, emphasizing the critical need for effective lipid-lowering interventions to mitigate cardiovascular risk.

Successful Treatment of Primary FSGS with LDL Apheresis

Successful Treatment of Primary FSGS with LDL Apheresis

Rapid Lipid-Lowering Response in Two Cases of Autosomal Recessive Hypercholesterolemia

BackgroundAutosomal recessive hypercholesterolemia (ARH) is an ultrarare dyslipidemia caused by variants in the LDLRAP1 gene. Clinically, this condition is indistinguishable from other homozygous familial hypercholesterolemia (HoFH). CaseWe present the cases of two siblings diagnosed with ARH caused by LDLRAP1 gene c.617-14C>A splicing homozygous variant. Over a five-year treatment period, the older sibling experienced an 81% reduction in low-density lipoprotein cholesterol (LDL-C) levels with the maximal dose of pitavastatin plus ezetimibe, while the younger sibling achieved a 75% reduction. After three sessions, the older brother no longer required LDL apheresis, and the sibling never had LDL apheresis. ConclusionOur findings demonstrate a rapid and significant response to lipid-lowering therapy (LLT) in patients with ARH caused by c.617-14C>A splicing VUS variant, a condition that mimics HoFH at diagnosis. Long-term follow-up studies in large pediatric cohorts of ARH patients treated with pitavastatin plus ezetimibe from childhood are necessary to better define the risk of cardiovascular disease (CVD) development.

Efficacy of Novel Low-Density Lipoprotein Apheresis for Chronic Limb-Threatening Ischemia

Efficacy of Novel Low-Density Lipoprotein Apheresis for Chronic Limb-Threatening Ischemia

High-Density Lipoprotein Subclasses and Their Role in the Prevention and Treatment of Cardiovascular Disease: A Narrative Review.

The association between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) is controversial. HDL-C is one content type of high-density lipoprotein (HDL). HDL consists of diverse proteins and lipids and can be classified into different subclasses based on size, shape, charge, and density, and can change dynamically in disease states. Therefore, HDL-C levels alone cannot represent HDLs' cardioprotective role. In this review, we summarized the methods for separating HDL subclasses, the studies on the association between HDL subclasses and cardiovascular risk (CVR), and the impact of lipid-modifying medications and nonpharmacological approaches (exercise training, dietary omega fatty acids, and low-density lipoprotein apheresis) on HDL subclasses. As HDL is a natural nanoplatform, recombinant HDLs (rHDLs) have been used as a delivery system in vivo by loading small interfering RNA, drugs, contrast agents, etc. Therefore, we further reviewed the HDL subclasses used in rHDLs and their advantages and disadvantages. This review would provide recommendations and guidance for future studies on HDL subclasses' cardioprotective roles.

Asymptomatic Intracranial Artery Stenosis/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events.

The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH. This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low-density lipoprotein cholesterol level (240±95 versus 244±75 mg/dL; P=0.67) did not differ between the 2 groups. Despite the use of lipid-lowering therapies (statin, P=0.71; high-intensity statin, P=0.81; ezetimibe, P=0.33; proprotein convertase subxilisin/kexin type 9 inhibitor, P=0.39; low-density lipoprotein apheresis, P=0.14), on-treatment low-density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97±62 versus 105±50 mg/dL; P=0.17), accompanied by a higher triglyceride level (median, 109 versus 79 mg/dL; P=0.001). During the 12.4-year observational period (interquartile range, 6.2-24.6 years), asymptomatic IASO exhibited a 4.04-fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71-9.55; P=0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71-10.9]; P=0.002). A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid-lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH-related atherosclerosis, which ultimately affects future outcomes.

#3006 Therapeutic apheresis in Fabry disease

Abstract Background and Aims Fabry's disease (FD) is a rare lysosomal disorder linked to the X chromosome due to a mutation in the gene encoding alpha-galactosidase A (alpha-Gal A). This mutation leads to a defect in the metabolism of glycosphingolipids, causing the progressive accumulation of globotriaacylceramide (GB3) or LysoGB3 in cells, tissues, and organs. In the treatment of FD, we have enzyme replacement therapy (ERT) with Agalsidase-alfa (Replagal®), Agalsidase-beta (Fabrazyme®), and chaperones (Migalastat®). However, there are limitations such as disease progression and morbimortality. Regarding ERT, the development of circulating immunoglobulin G (IgG) antibodies against agalsidase (aGAL) in the long term appears to be associated with a loss of effectiveness. The use of Therapeutic Apheresis (TA), such as plasma exchange therapy (PE) and low-density lipoprotein apheresis (LDL-apheresis), is employed in the treatment of various pathologies due to its ability to eliminate plasma, antibodies, low-density lipoproteins, apolipoproteins, and the adaptability of therapy to the molecule to be removed. The aim was to demonstrate that LDL-apheresis and PE favor Lyso-Gb3 elimination, and PE also eliminates IgG-aGAL as an adjunctive treatment in FD and conducted a proof-of-concept study. Method Two branches of intervention were established, where patients were classified into two groups based on the presence or absence of anti-agalsidase IgG antibodies. If they have the presence of antibodies, they would be eligible for plasma exchanges with two objectives: removing pre-formed antibodies and eliminating Lyso-Gb3. Conversely, in the absence of pre-formed antibodies, LDL-apheresis is performed with the aim of eliminating Lyso-Gb3. The proof-of-concept study was done with two FD patients undergoing ERT were identified, one with IgG-aGAL and the other with very low levels. PE was performed on the first patient, and LDL-apheresis on the second. Lyso-Gb3 levels were titrated in blood before and after LDL-apheresis, and in the washout bag of the column. For antibodies, titration was done in pre and post PE blood and in the extracted plasma from PE. Results After applying TA techniques, we observed that PE reduces IgG-aGAL by 85%, and in the case of LDL-apheresis, there was a 28% reduction in IgG-aGAL. While the ability to eliminate LysoGb3 showed a reduction of 25.5% in PE and 39.7% for LDL-apheresis. To eliminate a potential confounding factor, LysoGb3 determination in albumin was within normal limits. Conclusion With these results, we confirm that PE is more efficient in removing IgG-aGAL but also eliminates LysoGb3, whereas LDL-apheresis is a very effective technique for removing Lyso-Gb3 but also contributes to antibody removal. Based on these findings, we consider TA to be an effective adjunctive tool for FD treatment, even as a standalone treatment. However, these are very preliminary results and should be reproduced with a larger number of patients.

Management of Pregnancy in a Patient with Familial Hypercholesterolemia and Previous Myocardial Infarction—Treatment with LDL Apheresis: A Case Report

Familial hypercholesterolemia, a genetic disorder marked by elevated low-density lipoprotein cholesterol (LDL-C), poses significant risks for premature atherosclerosis and cardiovascular diseases, particularly during pregnancy. One of the safe methods of treating this condition in pregnancy is with the use of LDL apheresis. We present a 38-year-old primigravida with homozygous Familial Hypercholesterolemia (HoFH), ischemic cardiomyopathy, and angina pectoris. Two years before conception, extremely elevated lipid levels prompted statin therapy and lifestyle changes. Stent placements followed acute myocardial infarction. When planning pregnancy, statins were discontinued, but lipid levels elevated. LDL apheresis was initiated, achieving a 60% reduction. Throughout pregnancy, 16 LDL apheresis sessions were performed every 14 days, maintaining optimal lipid profiles. A cesarean section was performed in the 38th week of gestation, delivering a healthy infant. The patient resumed statin therapy after 8 months of breastfeeding. The patient maintained cardiovascular health, demonstrating the feasibility of controlled HoFH pregnancies. This case highlights the successful management of HoFH during pregnancy using LDL apheresis, ensuring maternal and fetal well-being. Future research on novel treatments and their safety during pregnancy is essential for refining therapeutic approaches in similar cases.

Consensus document on diagnosis and management of familial hypercholesterolemia from the Italian Society for the Study of Atherosclerosis (SISA)

AimsFamilial Hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism that causes an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Although early diagnosis and treatment of FH can significantly improve the cardiovascular prognosis, this disorder is underdiagnosed and undertreated. For these reasons the Italian Society for the Study of Atherosclerosis (SISA) assembled a Consensus Panel with the task to provide guidelines for FH diagnosis and treatment. Data synthesisOur guidelines include: i) an overview of the genetic complexity of FH and the role of candidate genes involved in LDL metabolism; ii) the prevalence of FH in the population; iii) the clinical criteria adopted for the diagnosis of FH; iv) the screening for ASCVD and the role of cardiovascular imaging techniques; v) the role of molecular diagnosis in establishing the genetic bases of the disorder; vi) the current therapeutic options in both heterozygous and homozygous FH. Treatment strategies and targets are currently based on low-density lipoprotein cholesterol (LDL-C) levels, as the prognosis of FH largely depends on the magnitude of LDL-C reduction achieved by lipid-lowering therapies. Statins with or without ezetimibe are the mainstay of treatment. Addition of novel medications like PCSK9 inhibitors, ANGPTL3 inhibitors or lomitapide in homozygous FH results in a further reduction of LDL-C levels. LDL apheresis is indicated in FH patients with inadequate response to cholesterol-lowering therapies. ConclusionFH is a common, treatable genetic disorder and, although our understanding of this disease has improved, many challenges still remain with regard to its identification and management.

Lomitapide: A Medication Use Evaluation and a Formulary Perspective.

Lomitapide is approved for lowering low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemia, which is a rare genetic disorder. The evidence regarding its safety and efficacy from a small clinical trial requires further validation for effectiveness and safety in the real world. This study aimed to use institutional data on the effectiveness and safety of lomitapide to assist in formulating a perspective on adding it to the formulary. This was a retrospective review of patients who were actively prescribed lomitapide at King Abdulaziz Medical City, Riyadh, Saudi Arabia, from 2019 to 2022. Data collection included demographics, confirmed gene mutation results, duration of lomitapide therapy, baseline, on-treatment, last LDL-C levels, percent reduction in LDL-C after 1-3 months of therapy (whichever was first available), other LDL-C lowering therapies used, liver function tests, adverse effects, and compliance. Eight adult patients were included in the review, with a mean age of 25.5 years. Approximately 75% were female, and the duration of treatment with lomitapide ranged from 9 months to 3 years. None of the patients were on continuous LDL apheresis. The mean baseline LDL-C at presentation to our facility was 17.2 mmol/L (range, 11.78-21.97 mmol/L), the mean percent drop in LDL-C with lomitapide was 34.1% (range, 0%-87%), gastrointestinal disturbances were documented in 50% of the patients, and no cases of severe liver toxicities or increase in liver enzymes were seen. In our cohort of adult patients, lomitapide showed an overall modest reduction in LDL-C, with no cases of increase in liver enzymes and documented intolerance, indicating that most patients were likely noncompliant. This review revealed important considerations when reimbursing expensive medications for rare diseases. Real-world evidence in real-time can support healthcare systems in price negotiations and reaching mutual agreements that can eventually improve patient access to care.

Research Progress in the Clinical Treatment of Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal dominant inheritable disease with severe disorders of lipid metabolism. It is mainly marked by increasing levels of plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), xanthoma, corneal arch, and early-onset coronary heart disease (CHD). The prevalence of FH is high, and it is dangerous and clinically underdiagnosed. The clinical treatment for FH includes both pharmacological and non-pharmacological treatment, of which non-pharmacological treatment mainly includes therapeutic lifestyle change and dietary therapy, LDL apheresis, liver transplantation and gene therapy. In recent years, many novel drugs have been developed to treat FH more effectively. In addition, the continuous maturity of non-pharmacological treatment techniques has also brought more hope for the treatment of FH. This paper analyzes the pathogenic mechanism and the progress in clinical treatment of FH. Furthermore, it also summarizes the mechanism and structure-activity relationship of FH therapeutic drugs that have been marketed. In a word, this article provides a reference value for the research and development of FH therapeutic drugs.

Facile Preparation of β-Cyclodextrin-Modified Polysulfone Membrane for Low-Density Lipoprotein Adsorption via Dopamine Self-Assembly and Schiff Base Reaction.

A facile method for the immobilization of β-cyclodextrin on polysulfone membranes with the aim of selectively adsorbing low-density lipoprotein (LDL) was established, which is based on the self-assembly of dopamine on the membrane followed by the Schiff base reaction with mono-(6-ethanediamine-6-deoxy)-β-cyclodextrin. The surface modification processes were validated using X-ray photoelectron spectroscopy and attenuated total reflectance Fourier-transform infrared spectroscopy. Surface wettability and surface charge of the membranes were investigated through the water contact angle and zeta potential analysis. The cyclodextrin-modified polysulfone membrane (PSF-CD) showed good resistance to protein solutions, as shown by the measurement of BSA adsorption. The assessment of BSA adsorption revealed that the cyclodextrin-modified polysulfone membrane (PSF-CD) exhibited excellent resistance to protein solutions. To investigate the adsorption and desorption behaviors of the membranes in single-protein or binary-protein solutions, an enzyme-linked immunosorbent assay was employed. The results revealed that the PSF-CD possessed remarkable adsorption capacity and higher affinity for LDL in both single-protein and binary-protein solutions, rendering it a suitable material for LDL apheresis.

Heparin-Mediated Extracorporeal Low-Density Lipoprotein Precipitation Apheresis for Treating Peripheral Arterial Disease in Patients with Chronic Kidney Disease.

Patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD), have a high prevalence of cardiovascular disease and peripheral arterial disease (PAD). Medical treatment is mainly based on risk factor management, and the surgical approach remains the gold standard treatment in specific conditions. Heparin-mediated extracorporeal low-density lipoprotein precipitation (H.E.L.P.) apheresis is effective in reducing circulating lipoprotein, fibrinogen, inflammatory mediators and procoagulant factors, thereby reducing cardiovascular risk in patients with familial hypercholesterolemia and hypertriglyceridemia. These activities may be effective in reducing symptoms and ischemic vascular lesions even in patients with severe PAD. We reported the application of a treatment protocol with H.E.L.P. apheresis in an ESRD patient with severe PAD without clinical improvement after severe revascularization who was not suitable for further surgical approaches, despite normal LDL cholesterol and lipoprotein (a). The H.E.L.P. protocol was characterized by an intensive first phase with weekly treatments followed by a single session every 10-15 days for 6 months of treatment. The overall clinical condition, foot lesions and walking distance improved significantly after the first 2 months of treatment, and foot amputation was avoided. Here, we review the main pathogenetic mechanisms through which LDL apheresis improves microcirculation and clinical outcomes. Its wider application may represent an optimal therapeutic option for patients unresponsive to standard treatment.

Low-density Lipoprotein Receptor Activities, Lipids, Apolipoprotein, and Clinical Course of Patients with Steroid-resistant Nephrotic Syndrome Treated with Low-density Lipoprotein Apheresis: A Case Series.

We herein report three cases of steroid-resistant nephrotic syndrome successfully treated with low-density lipoprotein apheresis (LDL-A). All patients were treated with a combination of steroids, cyclosporine, and LDL-A. In all cases, the serum concentrations of LDL, total and high-density lipoprotein cholesterol, and triglycerides were significantly lowered following LDL-A administration. Furthermore, the estimated LDL receptor activity increased, while both serum LDL and total cholesterol levels decreased, suggesting that LDL-A increases LDL receptor activity by driving changes in serum cholesterol concentration. This case series suggests that LDL-A increases LDL receptor activity, which may improve the intracellular uptake of cyclosporine.

Correlation between bradykinin concentration and blood pressure during Rheocarna therapy: A single-center case series.

A novel LDL (low-density lipoprotein) apheresis therapeutic option, Rheocarna, has garnered attention as an alternative therapy for chronic limb-threating ischemia (CLTI). Bradykinin-mediated vasodilation is involved in the effects of LDL apheresis and a decrease in blood pressure (BP), but the changes in bradykinin concentration during Rheocarna therapy are unknown. The study involved patients with CLTI treated with Rheocarna at our hospital, from April 2022 to August 2023. After Rheocarna therapy, skin ulcers improved in 80% of the patients. Circuit coagulation was observed in two patients with high fibrinogen levels. A decrease in BP was observed at approximately the same time when the bradykinin concentration peaked. The peak bradykinin concentration in a patient undergoing hemodialysis at the same time was considerably lower than that in the other patients. This is the first report on the changes in bradykinin concentration under Rheocarna therapy.

One-step engineering dual-network reinforced hydrogel microspheres with excellent anti-coagulant and low-density lipoprotein removal

Low-density lipoprotein apheresis (LDL-a) is a potent therapeutic strategy for treating hyperlipidemia and preventing atherosclerotic cardiovascular disease. However, the use of water-soluble anticoagulant during LDL-a treatment increases the risk of severe bleeding. In this study, dual-network composite polyacrylonitrile (PAN) hydrogel microspheres (CAHMs) are prepared through a one-step synthesis method using PAN, acrylic acid (AA) and 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS) as raw materials. Benefiting from the presence of PAN network, the CAHMs exhibit an average compressive stress of 7.16 MPa. Then, the hydrophilic network established by AA and AMPS leads to excellent LDL adsorption capacity and self-anticoagulant property, significantly inhibiting the activity of the blood coagulation factors VIII, IX, XI and XII, and prolonging the activated partial thromboplastin time (APTT) by fourfold. Moreover, according to the Sips model, the CAHMs exhibit a maximum static LDL adsorption capacity of 49.37 mg/g. In dynamic simulated perfusion experiments, the CAHMs achieve a total LDL adsorption capacity of 69.59 mg/g, 20 times higher than the adsorption capacity for HDL. The one-step synthesis method employed in this study guarantees rapid and large-scale production of the composite microspheres, which possess excellent mechanical strength, blood compatibility, self-anticoagulant property and LDL adsorption capacity. This one-step synthesis method has the advantage of abandoning organic solvent and stabilizer, thus provides a new idea for the industrial preparation of LDL absorbent used in whole blood.

Updated evidence of beneficial effect of LDL apheresis for refractory nephrotic syndrome due to a variety of causative diseases for nationwide and global approval.

Low-density lipoprotein apheresis (LDL-A) therapy has shown reasonable efficacy in treating nephrotic syndrome (NS) refractory to initial drug therapy and has been covered by National Health Insurance for the indication of drug-resistant focal segmental glomerulosclerosis (FSGS) since 1992 in Japan and has contributed to liberating substantial number of patients of this disease from entering into end-stage renal disease by easier practical application in actual clinical settings. Subsequently, various beneficial evidence of this treatment has accumulated on those other than FSGS, however, due to the limitation of covered disease insurance only for FSGS, patients with diseases other than FSGS are unlikely to benefit from this treatment in practice. This review summarizes the therapeutic evidence of the beneficial effect of LDL-A accumulated to date and the mechanisms of action analyzed from multifaceted perspectives. examines the applicability of expanding insurance coverage for diseases other than FSGS.

Evaluation of the treatment volume and removal rate of Rheocarna: A novel adsorption-type blood purification device for patients with chronic limb-threatening ischemia.

Chronic limb-threatening ischemia (CLTI) is a clinical syndrome defined by peripheral arterial disease (PAD) combined with rest pain, gangrene, or leg ulceration for longer than two weeks resulting in lower extremity amputation. In recent years, low-density lipoprotein apheresis (LDL-A) has been implemented for PAD treatment. However, it has not been possible to ensure insurance coverage for patients with lower LDL levels than 140 mg/dL under cholesterol-lowering drugs. Rheocarna is a novel adsorption-type blood purification device for the treatment of CLTI by adsorbing LDL and fibrinogen (Fib) that is not constrained by hypercholesterolemia and is not amenable to or nonresponsive to revascularization surgery. The only requirements for use are that the blood flow rate increases up to 200 mL/min gradually. To evaluate the applicability of this treatment procedure, we compared the removal rates of Fib and LDL following Rheocarna therapy using various blood treatment volumes (6, 10.5, and 19.5 L). Fib and LDL removal rates were about 20% and 15%-25% per treatment, with no significant differences between treatment volumes. Following treatment with Rheocarna, blood pressure tends to decrease at first, which later increases, and the higher the treatment volume, the longer the time of low blood pressure tended to be. Although no significant difference was found in the removal rate of Fib and LDL in response to increase volume to 6 L or beyond in this study, the 6 L volume is considered effective enough for the removal of Fib and LDL.