Effects Of Low-density Lipoprotein Apheresis Research Articles

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.

Effect of Low-Density Lipoprotein Apheresis on Quality of Life in Patients with Diabetes, Proteinuria, and Hypercholesterolemia

Introduction: Treating diabetic nephropathy with low-density lipoprotein (LDL) apheresis reduces proteinuria and improves prognosis. However, its impact on patients’ quality of life (QoL) is unclear. This study evaluated the effect of LDL apheresis on QoL in patients with diabetes, proteinuria, and hypercholesterolemia. Methods: In this nationwide multicenter prospective study, we enrolled 40 patients with diabetes. Inclusion criteria were proteinuria (defined as an albumin/creatinine ratio ≥3 g/g), serum creatinine levels <2 mg/dL, and serum LDL ≥120 mg/dL despite drug treatment. LDL apheresis was performed 6–12 times within 12 weeks. The 36-item Short Form Health Survey (SF-36) was used to analyze QoL. Results: The study enrolled 35 patients (27 men and 8 women; mean age 58.9 ± 11.9 years). A comparison of baseline SF-36 values with those at the end of the course of apheresis found an improvement in the mean physical component summary (37.9 ± 11.4 vs. 40.6 ± 10.5, p = 0.051) and a significant increase in the mean mental component summary (MCS) (49.4 ± 8.4 vs. 52.5 ± 10.9, p = 0.026). A multivariable linear regression analysis revealed a history of coronary heart disease negatively correlated with the MCS increase at the end of the course of apheresis (β coefficient −6.935, 95% confidence interval, 13.313 to−0.556, p = 0.034). Conclusion: Our results suggest that LDL apheresis may improve the mental and physical QoL in patients with diabetes, proteinuria, and hypercholesterolemia.

Effects of LDL apheresis on proteinuria in patients with diabetes mellitus, severe proteinuria, and dyslipidemia

Patients with diabetes mellitus and severe proteinuria present with poor renal prognoses, despite improvements in diabetes and kidney disease therapies. In this study, we designed a low-density lipoprotein (LDL)-cholesterol apheresis treatment for patients with diabetic nephropathy (DN)/diabetic kidney disease and severe proteinuria. This was a multicenter prospective LICENSE study to confirm the impact of LDL apheresis on proteinuria that exhibited hyporesponsiveness to treatment. In addition, we sought to determine the efficacy and safety of LDL apheresis by comparing the outcomes to those of historical controls in patients with diabetes, refractory hypercholesterolemia, and severe proteinuria. This was a prospective, multicenter study, including 40 patients with diabetes, severe proteinuria, and dyslipidemia. LDL apheresis was performed 6-12 times over a 12-week period. The primary endpoint was the proportion of patients with a decrease in proteinuria excretion of at least 30% in the 6months after starting therapy. The secondary endpoints included serum creatinine levels and laboratory variables, which were evaluated 4, 6, 12, 18, and 24months after therapy initiation. LDL apheresis was performed on 40 registered patients with diabetes. The proportion of cases in which proteinuria decreased by 30% or more after 6months of LDL apheresis was 25%, which was similar to that of historical controls. The overall survival and end-stage kidney disease-free survival rates were significantly higher in the LICENSE group compared to those in historical controls. Our results suggest that LDL apheresis may be effective and safe for patients with diabetes, proteinuria, and dyslipidemia. Trial registration number: jRCTs042180076.

Evaluation of vascular quality of life questionnaire in dialysis patients with peripheral arterial disease treated by low-density lipoprotein apheresis

Peripheral arterial disease (PAD) is a common complication in dialysis patients. Early diagnosis and treatment are recommended. Low-density lipoprotein apheresis (LDL-A) is a potential therapy to improve PAD. However, the mechanism has yet to be fully clarified due to lack of established quantitative methods to assess the therapeutic effects of LDL-A treatment. Improvement of skin perfusion pressure (SPP) or ankle brachial index (ABI) is a representative therapy goal, but clinical symptoms were not always consistent with the values of SPP/ABI. Vascular quality of life questionnaire (VascuQOL) was proposed as a disease-specific QOL score, getting validated recently. The possibility of VascuQOL to reflect the severity of PAD in dialysis patients and evaluate the therapeutic effects of LDL-A has yet to be elucidated. This is an observational study. LDL-A treatment was performed in 32 dialysis patients with PAD. They were divided to critical limb ischemia (CLI) group (17 subjects) and non-CLI group (15 subjects) according to their clinical manifestations. We examined the relationship of PAD severity with SPP, ABI, VascuQOL, and lipid profile such as apoB/apoA-I ratio, malondialdehyde-modified LDL, and remnant-like particles cholesterol. Furthermore, we evaluated these parameters successively to find out a suitable therapeutic marker just after the first LDL-A, at tenth LDL-A, and 1 month after completion of LDL-A treatment. All of the lipid markers were higher in CLI patients, but not significantly different from those in the non-CLI group. They decreased significantly just after LDL-A, although no changes were observed 1 month after completion of LDL-A treatment. ABI was significantly different between the CLI and non-CLI groups, but did not improve by LDL-A treatment. By contrast, SPP was ameliorated significantly and the peak was at tenth LDL-A. Among VascuQOL domains, “Symptom” and “Emotional” domains were significantly different between the CLI and non-CLI groups. The average score of VascuQOL increased successively until 1 month after completion of LDL-A treatment. Several domains of VascuQOL can reflect the severity of PAD in dialysis patients. VascuQOL was a useful marker to show the prolonged therapeutic effects of LDL-A treatment in dialysis patients with PAD, independent of SPP.

Low-density lipoprotein apheresis ameliorates monthly estimated glomerular filtration rate declines in patients with renal cholesterol crystal embolism.

The incidence of cholesterol crystal embolism (CCE) has increased along with increases in the prevalence of atheromatous diseases and intravascular procedures. CCE frequently results in the deterioration of renal function, which sometimes leads to end-stage renal failure. Although there has been no established therapy for CCE, the possibility that low-density lipoprotein apheresis (LDL-A) is an effective therapy for renal CCE was previously reported. However, whether LDL-A improves renal CCE remains uncertain. This study aimed to evaluate the effectiveness of LDL-A in renal CCE patients. Twelve renal CCE patients (9 men and 3 women, mean age 70.6 ± 1.7 years) were included in this retrospective study. All patients had received LDL-A therapy, and estimated glomerular filtration rate (eGFR) values were examined before and after LDL-A. In addition, monthly changes in eGFR before and after LDL-A were calculated for each patient. At initial diagnosis of renal CCE, the eGFR was 35.2 ± 4.8 mL/min/1.73 m(2). At the initiation of LDL-A, the eGFR significantly decreased to 11.0 ± 1.2 mL/min/1.73 m(2), and monthly changes in eGFR reached -7.2 ± 2.5 mL/min/1.73 m(2)/month. After the initiation of LDL-A, the progression of renal dysfunction stabilized in nearly two-thirds of patients, and monthly changes in eGFR after LDL-A significantly diminished to -0.3 ± 0.7 mL/min/1.73 m(2)/month (p < 0.05 vs. before LDL-A). Although 4 patients had to undergo hemodialysis, all patients were alive over 1 year after the initiation of LDL-A. LDL-A therapy ameliorated renal dysfunction in renal CCE patients.

The effect of low-density lipoprotein apheresis on ocular microcirculation in patients with hypercholesterolaemia: a pilot study

AimTo investigate the effect of low-density lipoprotein (LDL) apheresis on ocular microcirculation in patients with hypercholesterolaemia.MethodsSix patients with hypercholesterolaemia were included in this study. The diameter of retinal vessels was...

Effect of Low-Density Lipoprotein Apheresis on Plasma Levels of Apolipoprotein E4

Apolipoprotein E4 (apoE4) is a positively charged proinflammatory apolipoprotein bound to high-density lipoprotein (HDL) cholesterol and remnant lipoproteins. ApoE4 is associated with an increased risk of cardiovascular and cerebrovascular disease. Low-density lipoprotein (LDL) apheresis, a therapy for patients with familial hypercholesterolemia, removes apolipoprotein B and other positively charged plasma proteins but negatively charged proteins such as HDL cholesterol are generally spared. Despite their negative charge, LDL apheresis still removes 10% to 15% of HDL cholesterol, in particular, inflammatory HDL cholesterol. Patients with familial hypercholesterolemia have increased plasma levels of apoE4 and apoE4-bound HDL cholesterol. We tested the hypothesis that LDL apheresis would reduce the plasma levels of apoE4. We analyzed the plasma apoE4 levels using enzyme-linked immunosorbent assay immediately before and after LDL apheresis in 10 patients with familial hypercholesterolemia who had tested positive for the apoE4 isoform. After one treatment, the mean plasma apoE4 levels had been reduced by 39%, LDL cholesterol by 75%, triglycerides by 38%, and HDL cholesterol by 18%. The change in HDL cholesterol was significantly related to the apoE4 baseline values (r = -0.83, p = 0.001) and apoE4 levels after apheresis (r = 0.816, p = 0.004). In conclusion, LDL apheresis acutely reduced the plasma levels of apoE4. The mechanism of apoE4 reduction by LDL apheresis might be related to the selective reduction of a particular HDL cholesterol.

The role of dysfunctional HDL in atherosclerosis

This review focuses on HDL function in modulating LDL oxidation and LDL-induced inflammation. Dysfunctional HDL has been identified in animal models and humans with chronic inflammatory diseases including atherosclerosis. The loss of antiinflammatory function correlated with a loss of function in reverse cholesterol transport. In animal models and perhaps in humans, dysfunctional HDL can be improved by apoA-I mimetic peptides that bind oxidized lipids with high affinity.

Effect of Low-Density Lipoprotein Apheresis on Inflammatory and Noninflammatory High-Density Lipoprotein Cholesterol

Low-density lipoprotein (LDL) apheresis, a treatment for familial hypercholesterolemia, significantly decreases LDL cholesterol and inflammatory markers such as C-reactive protein, CD40 ligand, and tissue factor. LDL apheresis also decreases high-density lipoprotein (HDL) cholesterol, which might be considered therapeutically counterproductive because HDL is known to be anti-inflammatory. However, recent studies have shown that HDL also possesses proinflammatory properties, as seen in its ability to alter LDL-induced monocyte chemotactic activity. We examined the acute effects of LDL apheresis on inflammatory HDL activity in 13 patients with familial hypercholesterolemia and cardiovascular disease who had been receiving bi-weekly LDL apheresis treatments. Immediately before and immediately after treatment, each patient's plasma was collected for analysis of inflammatory HDL and full lipid profile. LDL apheresis reduced LDL by 52% (from 208 +/- 89 to 99 +/- 48 mg/dl, p <0.002), and HDL decreased by 16% (49 +/- 15 to 41 +/- 13 mg/dl, p <0.003). At the same time, inflammatory HDL activity (in migrated monocytes per high-power field) decreased from 22 +/- 4 to 14 +/- 2, a 37% acute reduction (p <0.003). Moreover, inflammatory HDL before HDL apheresis was highly correlated with its acute reduction (r(s) = 0.85, p <0.001). In conclusion, our findings indicate that, in addition to decreasing LDL, LDL apheresis also decreases inflammatory HDL. The clinical significance of reducing inflammatory HDL is currently unknown, and further research is needed to examine its potential benefit for cardiovascular disease.

Beneficial effect of low-density lipoprotein apheresis (LDL-A) on refractory nephrotic syndrome (NS) due to focal glomerulosclerois (FGS)

Hypercholesterolemia is one of the factors which deteriorate renal function in NS especially due to FGS. LDL-A is a potential option for treating NS due to FGS accompanied by hypercholesterolemia and resistant to conventional drug therapy with steroids and/or cyclosporine A (CsA). As reported by Muso et al. [2001], LDL-A combined with drug therapy yields more rapid relief from NS and better prognosis than drug therapy alone. However, very limited data are available on outcome at several years after treatment. The aim of this study was to clarify long-term outcome of NS patients treated with LDL-A and to evaluate the effectiveness of this treatment. To clarify the long-term outcome of LDL-A, we conducted a retrospective survey on outcome up to 5 years. From 36 hospitals in Japan, 41 patients with NS whose short-term outcomes with LDL-A were reported from 1999-2004 were collected and analyzed. In all, 29 and 15 patients with outcomes determined at 2 and 5 years after treatment, respectively, were obtained. At 2 and 5 years after treatment, 62 and 87% of patients, respectively, were classified into complete or Type 1 incomplete remission. The strength of correlations between outcome and several factors including parameters of renal function measured before and after treatment and treatment condition revealed that early administration of LDL-A after the onset of NS provided a good long-term outcome. The data also suggest that more drastic decrease of LDL favored a better prognosis. In NS due to FGS treated with LDL-A, long-term outcome was as good as short-term outcome. Early administration of LDL-A after the onset of NS provided a good long-term outcome. To obtain more precise findings regarding the effects of this treatment, a large-scale prospective study will be needed.

Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions

The atherogenicity theory for triglyceride-rich lipoproteins (TRLs; VLDL + intermediate density lipoprotein) generally cites the action of apolipoprotein C-III (apoC-III), a component of some TRLs, to retard their metabolism in plasma. We studied the kinetics of multiple TRL and LDL subfractions according to the content of apoC-III and apoE in 11 hypertriglyceridemic and normolipidemic persons. The liver secretes mainly two types of apoB lipoproteins: TRL with apoC-III and LDL without apoC-III. Approximately 45% of TRLs with apoC-III are secreted together with apoE. Contrary to expectation, TRLs with apoC-III but not apoE have fast catabolism, losing some or all of their apoC-III and becoming LDL. In contrast, apoE directs TRL flux toward rapid clearance, limiting LDL formation. Direct clearance of TRL with apoC-III is suppressed among particles also containing apoE. TRLs without apoC-III or apoE are a minor, slow-metabolizing precursor of LDL with little direct removal. Increased VLDL apoC-III levels are correlated with increased VLDL production rather than with slow particle turnover. Finally, hypertriglyceridemic subjects have significantly greater production of apoC-III-containing VLDL and global prolongation in residence time of all particle types. ApoE may be the key determinant of the metabolic fate of atherogenic apoC-III-containing TRLs in plasma, channeling them toward removal from the circulation and reducing the formation of LDLs, both those with apoC-III and the main type without apoC-III.

Urinary liver-type fatty acid-binding protein levels for differential diagnosis of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and effect of low-density lipoprotein apheresis

Focal glomerulosclerosis (FGS) and minor glomerular abnormalities are kidney diseases characterized by massive proteinuria. Urinary liver-type fatty acid-binding protein (L-FABP), an intracellular carrier protein of free fatty acids, is expressed in proximal tubules of the human kidney. Patients with FGS show significant improvement with low-density lipoprotein (LDL) apheresis. The aim of the present study was to determine whether urinary L-FABP levels differ between patients with FGS and those with minor glomerular abnormalities and whether levels are altered by LDL apheresis. There were 24 patients with minor glomerular abnormalities (nephrotic stage, n = 14, remission stage, n = 10), 17 patients with FGS, and 20 healthy age-matched subjects were included in the present study. Urinary L-FABP levels were measured by enzyme-linked immunosorbent assay and compared. All patients with minor glomerular abnormalities at the nephrotic stage received prednisolone for 6 months, and all FGS patients received some form of immunosuppression therapy with prednisolone, cyclophosphamide or mizoribine for 12 months. LDL apheresis was performed in eight FGS patients with drug-resistant nephrotic syndrome. Urinary L-FABP levels were significantly higher in the 17 FGS patients (82.0 +/- 44.4 microg/g.Cr) than in the 24 patients with minor glomerular abnormalities (10.2 +/- 8.4 microg/g.Cr) (p < 0.01) and in the 20 healthy subjects (7.4 +/- 4.2 microg/g.Cr) (p < 0.01). Urinary L-FABP levels differed little between nephrotic stage and remission stage in patients with minor glomerular abnormalities. Urinary L-FABP levels were significantly higher in the eight drug-resistant FGS patients (122.6 +/- 78.4 microg/g.Cr) than in the nine drug-sensitive FGS patients (45.9 +/- 32.0 microg/g.Cr). Urinary L-FABP levels did not correlate with levels of other clinical markers including serum creatinine, urinary protein, and urinary N-acetyl-beta-D- glucosaminidase. In the eight drug-resistant FGS patients, LDL-apheresis significantly reduced urinary protein excretion (p < 0.01) and urinary L-FABP levels (p < 0.01). Urinary L-FABP may be a useful diagnostic indicator for differentiation between FGS and minor glomerular abnormalities. LDL apheresis may be effective in ameliorating tubulointerstitial lesions associated with FGS.

Effect of Low-Density Lipoprotein Apheresis on Lipoprotein-Associated Phospholipase A 2

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a proinflammatory participant in atherosclerosis and a potential biomarker for coronary heart disease. The effects of low-density lipoprotein (LDL) apheresis on Lp-PLA(2) levels were evaluated in 8 patients with cardiovascular disease. Each patient received 5 LDL apheresis treatments over a 3-month period. The mean direct LDL cholesterol level reduction was 60% (252 to 100 mg/dl). LDL apheresis acutely reduced Lp-PLA(2) by 21.4%. Over the course of treatment, Lp-PLA(2) levels were reduced by 29%. Chronic LDL apheresis significantly reduces Lp-PLA(2) independent of LDL cholesterol, which may be a potential mechanism by which LDL apheresis diminishes coronary heart disease risk.

Effect of low-density lipoprotein apheresis on urinary protein and podocyte excretion in patients with nephrotic syndrome due to diabetic nephropathy

The aim of the present study is to determine whether low-density lipoprotein (LDL) apheresis affects proteinuria and urinary podocyte excretion in patients with type 2 diabetes and nephrotic syndrome. LDL apheresis was performed on patients with diabetes with long-standing nephrotic syndrome, and urinary protein level and number of urinary podocytes were compared between these patients (5 men, 3 women; mean age, 54.6 years) and 10 nephrotic patients with diabetes not treated with LDL apheresis (6 men, 4 women; mean age, 56.5 years). LDL apheresis reduced total cholesterol (P < 0.001), LDL cholesterol ( P < 0.001), lipoprotein(a) (P < 0.001), creatinine (P < 0.05), and blood urea nitrogen (P < 0.05) levels and increased creatinine clearance (P < 0.05). The LDL apheresis group showed a significant decrease in urinary protein excretion (from 10.8 +/- 3.2 to 1.8 +/- 1.1 g/d; P < 0.001) and number of urinary podocytes (from 4.8 +/- 2.2 to 0.9 +/- 0.4 cells/mL; P < 0.01). These data suggest that LDL apheresis effectively reduces proteinuria and podocyte excretion, ameliorating renal dysfunction in patients with nephrotic syndrome caused by diabetic nephropathy.

Effect of low-density lipoprotein cholesterol apheresis on blood viscosity

Few studies have been designed to study the hemodynamic effects of low-density lipoprotein apheresis, especially on whole blood viscosity. Six patients with cardiovascular disease and hypercholesterolemia underwent a single low-density lipoprotein apheresis, resulting in significant reductions in whole blood viscosity at all shear rates.

Effect of low-density lipoprotein apheresis on plasma endothelin-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans

Endothelin (ET)-1 has been implicated in the pathogenesis of diabetes, arteriosclerosis, and chronic renal failure. We studied whether low-density lipoprotein (LDL) apheresis alters plasma ET-1 levels in diabetic hemodialysis patients with arteriosclerosis obliterans (ASO). Plasma ET-1 levels were measured in 30 healthy control subjects (Group A), 30 diabetes patients without ASO (Group B), 20 diabetes patients with ASO (Group C), 20 diabetes patients without ASO who were undergoing hemodialysis (Group D), and 6 diabetes patients with ASO who were undergoing hemodialysis (Group E). Hemodialysis patients were dialyzed three times weekly with a bicarbonate dialysate. Six diabetic hemodialysis patients with ASO underwent LDL apheresis once weekly for 10 weeks, and the change in plasma ET-1 levels due to LDL apheresis was measured. LDL apheresis resulted in a statistically significant decrease in levels of total cholesterol and LDL cholesterol. In addition, LDL apheresis improved clinical symptoms in all patients. Plasma ET-1 levels in Group E (15.0±1.9 pg/ml) were significantly higher than those in Groups A (1.0±0.6 pg/ml, P<.001), B (1.3±0.5 pg/ml, P<.001), C (5.6±1.0 pg/ml, P<.001), and D (10.4±1.6 pg/ml, P<.01). Plasma ET-1 levels decreased progressively and significantly after a single LDL apheresis began (9.4±1.0 pg/ml after 60 min, P<.001, and 6.0±1.0 pg/ml after 120 min, P<.001). These data suggest that ET-1 may be associated with arteriosclerosis and that LDL apheresis enhances peripheral microcirculation in part by reducing the production of ET-1 in diabetic hemodialysis patients with ASO.

Changes in oxidative stress and microcirculation by low-density lipoprotein apheresis.

Low-density lipoprotein apheresis (LDLA) leads to an improvement of microcirculation during the very early stages of treatment, and continued treatment may produce antiatherogenic effects in patients with peripheral arterial disease (PAD). Suppression of oxidative stress, improvement of endothelial functions and alteration in the action of vasoactive compounds may occur with the improvement of the rheological property of blood as a result of aggressive removal of atherogenic factors including LDL, possibly resulting in the suppression of development of atherosclerosis. As these effects of LDLA may ameliorate not only PAD but also ischemia in other organs, it is suggested that repeated LDLA prevents the progression of atherosclerotic diseases and probably improves the long-term prognosis of patients with PAD.

Acute effects of low-density lipoprotein apheresis (HELP procedure) on cholesterol oxidation products and novel vasoactive substances urotensin and relaxin

Acute effects of low-density lipoprotein apheresis (HELP procedure) on cholesterol oxidation products and novel vasoactive substances urotensin and relaxin

P2356 Acute effects of low-density lipoprotein apheresis (HELP procedure) on cholesterol oxidation products and novel vasoactive peptides urotensin and relaxin

P2356 Acute effects of low-density lipoprotein apheresis (HELP procedure) on cholesterol oxidation products and novel vasoactive peptides urotensin and relaxin

Effects of low-density lipoprotein apheresis on coronary and carotid atherosclerosis and diabetic scleredema in patients with severe hypercholesterolemia.

Correlations between serum cholesterol levels and progression of coronary and peripheral atherosclerosis have been found in many recent studies. It has also been demonstrated that aggressive cholesterol-lowering therapy with low-density lipoprotein (LDL) apheresis, a method of LDL elimination by extracorporeal circulation, is effective not only for coronary artery disease, but also for systemic circulatory disturbance in severe hypercholesterolemic patients with familial hypercholesterolemia (FH) in particular. We found that LDL apheresis treatment with medical therapy improved coronary atherosclerotic lesions, based on coronary angiography evaluation and histopathological observation, suppressed progression of early carotid atherosclerotic lesions on annual B-mode ultrasonography, and improved diabetic scleredema in FH patients. This effectiveness of LDL apheresis appears to be due to recovery of vascular endothelial function and improvement of blood rheology. For diseases that are possibly due to circulation disturbance and that are intractable with drugs alone. LDL apheresis may be worth trying, particularly for patients complicated by hyperlipemia.