Lipoprotein apheresis is an optimal therapeutic option to reduce increased Lp(a) levels.

BACKGROUND: Lipoprotein(a) (Lp(a)) is a genetic risk factor for cardiovascular disease (CVD) and is associated with the induction and sustaining of atherosclerotic cardiovascular diseases (ASCVD). Since 2008 Lp(a) along with progressive CVD has been approved as an indication for regular lipoprotein apheresis (LA) in Germany. The German Lipoprotein Apheresis Registry (GLAR) has been initiated to provide statistical evidence for the assessment of extracorporeal procedures to treat dyslipidemia for both LDL-cholesterol (LDL-C) and Lp(a). The GLAR now allows prospective investigations over a 5-year period about annual incidence rates of cardiovascular events. Here Lp(a) patients (LDL-C < 100 mg/dl; Lp(a) > 60 mg/dl or >120 nmol/l) showed the same reduction of major coronary (83%) and non-coronary events (63%) as had been formerly shown in the Pro(a)LiFe study. However, Lp(a) is not only an apolipoprotein(a) (apo(a)) and LDL-C containing particle, which is covalently bound to a LDL-C core by a disulphide bridge. The composition of this particle, inter alia containing oxidized phospholipids, gives pro-atherosclerotic, pro-inflammatory, and pro-thrombotic properties, inducing atherosclerotic processes mainly in the arterial wall. However, recent investigations have shown that a reduction of inflammatory settings without LDL-C or Lp(a) reduction may reduce ASCVD events. Lipoprotein apheresis (LA) could not only reduce LDL-C and Lp(a) in parallel, but also different inflammatory and coagulation parameters. In summary lipoprotein apheresis is not only anti-atherosclerotic, but also anti-inflammatory and anti-thrombotic and therefore an ideal treatment option with respect to the shown reduction of major adverse coronary events (MACE) and major adverse non-coronary events (MANCE) by reducing Lp(a) levels.

Treatment-related and health-related quality of life in lipoprotein apheresis patients.

BACKGROUND: There is evidence for beneficial effects of lipoprotein apheresis (LA) in terms of reduction of cardiovascular events and interventions, but quality of life (QOL) in LA patients has only been explored in small samples. OBJECTIVE: In this study, both LA- or treatment-related and health-related QOL (HRQOL) were assessed in 206 LA patients. METHODS: Mental and physical HRQOL of the LA patients was assessed by means of the SF-12 as well as the EQ-5D. Physical complaints were assessed by the Patient Health Questionnaire-15 and LA- or treatment-related QOL by the Apheresis Quality of Life Form, developed for this study. RESULTS: Comparison with general population norms showed that LA patients scored significantly lower on HRQOL and significantly higher on physical complaints. A higher perceived impact of the treatment proved to have a significant negative association with HRQOL and a positive one with physical complaints. CONCLUSION: Previous studies reported higher levels of QOL in LA patients. This study showed that treatment-related QOL contributes to HRQOL and physical complaints in LA patients. While many patients do not experience LA as a real burden and report positive effects of the treatment, there is also an important group of patients for whom this is not the case. Although the impact on QOL of LA patients does most probably not outweigh the cardiovascular benefits of the treatment, it is important to screen treatment-related QOL in LA patients to optimize care in a personalized way. Future research is needed to compare QOL in LA with non-LA patients with similar medical conditions.

Current insights into the German lipoprotein apheresis standard: PCSK9-inhibitors, lipoprotein apheresis or both?

According to current European guidelines, lipid lowering therapy for progressive cardiovascular disease including cardiovascular events has to be focused on a target level for LDL-C. In contrast for Lp(a) a threshold has to be defined with respect to the method of measurement. However, due to new lipid lowering drug developments like PCSK9-inhibitors (PCSK-9-I) a therapeutic algorithm for patients with severe hypercholesterolemia or isolated Lipoprotein(a)-hyperlipoproteinemia with progressive cardiovascular disease may be necessary to manage the use of PCSK9-I, lipoprotein apheresis (LA) or both. The therapeutic approach for patients with homozygous familial hypercholesterolemia is unambiguous: In addition to LA, in order to improve LDL-C reduction, PCSK9-I could be applied. In patients with heterozygous familial hypercholesterolemia, PCSK9-I is to be applied first. If in addition to a pronounced LDL-C elevation, cardiovascular complications exist or if imaging techniques documented atherosclerotic changes pre-disposing for a cardiovascular event while LDL-C reduction is insufficiently reduced (LDL-C > 100 mg/dl (2.6 mmol/l)), LA treatment should then be applied as last resort. In patients with elevated Lp(a) concentrations (Lp(a) > 60 mg/dl (>120 nmol/l)) and established cardiovascular disease, therapy should rely primarily on LA methods. If in addition to high Lp(a) levels insufficiently treated LDL-C concentrations (LDL-C > 100 mg/dl (2.6 mmol/l)) exist, in rare cases PCSK9-I can supplement the lipid lowering concept.

Current insights into the German Lipoprotein Apheresis Registry (GLAR) - Almost 5 years on.

BACKGROUND: In recent years the Federal Joint Committee (G-BA), a paramount decision-making body of the German health care system required a reassessment of the approval of chronic lipoprotein apheresis therapy for regular reimbursement. Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology. In 2009 the working group completed the indication for lipoprotein apheresis with respect to current cardiovascular guidelines and current scientific knowledge for the registry. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data acquired over nearly 5 years can now be reported. METHODS AND RESULTS: All data were collected and analyzed during the time period 2012-2015. Over this time interval, 68 German apheresis centers collected retrospective and prospective observational data of 1.283 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-cholesterol (LDL-C) levels and/or high lipoprotein(a) (Lp(a)) levels suffering from progressive cardiovascular disease (CVD). A total of 15,167 documented LA treatments were investigated. All patients treated by LA exhibited a median LDL-C reduction rate of 68.6%, and a median Lp(a) reduction rate of 70.4%. Analogue to the Pro(a)LiFe pattern, patient data were analyzed and compared with respect to the incidence rate of coronary events (MACE) 1 and 2 years before the start of LA treatment (y-2 and y-1) and prospectively one year on LA treatment (y+1). During the first year of LA treatment a MACE reduction of 97% was be observed. In the years considered, LA treatment side effects occurred at a low rate (ca. 5%) and mainly comprised puncture problems. CONCLUSIONS: For the first time data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive CVD and maximally tolerated lipid lowering medication. In addition LA treatments were found to be safe, exhibiting a low rate of side effects.

The German Lipoprotein Apheresis Registry (GLAR) - almost 5 years on.

BACKGROUND: Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology and of Lipidologists and completed the data set for the registry according to the current guidelines and the German indication guideline for apheresis in 2009. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data are available over nearly 5 years now. METHODS AND RESULTS: During the time period 2012-2016, 71 German apheresis centers collected retrospective and prospective observational data of 1435 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-C levels and/or high Lp (a) levels suffering from cardiovascular disease (CVD) or progressive CVD. A total of 15,527 completely documented LA treatments were entered into the database. All patients treated by LA showed a median LDL-C reduction rate of 67.5%, and a median Lp (a) reduction rate of 71.1%. Analog to the Pro(a)LiFe pattern, patient data were analyzed to the incidence rate of coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y­1) and prospectively two years on LA treatment (y + 1 and y + 2). During two years of LA treatment a MACE reduction of 78% was observed. In the years considered, side effects of LA treatment were low (5.9%) and mainly comprised puncture problems. CONCLUSIONS: The data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp (a) levels, progressive CVD, and maximally tolerated lipid lowering medication. In addition, LA treatments were found to be safe with a low rate of side effects.

How to optimize lipoprotein apheresis treatment--a second look.

BACKGROUND: Lipoprotein apheresis (LA) is used in hypercholesterolemic patients suffering from cardiovascular disease (CHD) if a modified diet and lipid-lowering drug regimens had failed. During the first LA treatments LDL-cholesterol (LDL-C) and lipoprotein (a) (Lp(a)) can be decreased very effectively when using generally accepted formulas for calculating plasma (PV) (e.g. Pearson) or blood volumes (BV) as a basis for calculating treatment volume (e.g. Nadler). With respect to LDL-C and Lp(a) levels after LA treatment not all treated patients on steady state with apheresis treatment procedures may achieve the desired target concentrations for LDL-C (<70 mg/dl) and Lp(a) (<30 mg/dl). Are there further ways to increase the effectiveness of LA? METHODS: Over months or years of LA the treated volumes were stepwise increased in patients to achieve target cholesterol concentrations but not sufficiently in all cases. Therefore the patients' actual LA treatment volumes were compared to the calculated PV or BV. To possibly optimize the treatment capacity of LA procedures independent of calculated PV or BV the capacity threshold was determined in addition. During LA procedures every 20 min cholesterol, triglycerides, LDL-C, HDL-C and Lp(a) concentrations were determined and related to the hematocrit to exclude dilution effects. RESULTS: In patients undergoing regular LA treated volumes vs. calculated volumes were different: for PV 28 ± 18% (n = 7); for BV 28 ± 20% (n = 6). The mean treated volumes were 1.3 fold larger than the calculated volumes to achieve cholesterol target levels in most LA treatments. With respect to the capacity threshold we observed in only 1 of 13 patients an ineffective long treatment time. No LA procedure failed due to exhausted capacity. CONCLUSIONS: Lipoprotein apheresis treatment is a very effective treatment procedure in lowering LDL-C and Lp(a). However, not in all procedures the optimal treatment volume for LA patients may be calculated. However calculations of PV and BV are more or less error-prone. An increase of 1.3 fold in the calculated volumes may be the first step in optimizing individual LA treatment options. In addition, to exclude an exhaustion of LA procedures the determination of the individual capacity threshold in every LA patient may be further helpful to adjust treatment volumes. To substantiate our demand on changed treatment volumes further data are necessary.

An erythropoietin gene polymorphism in the hypoxia-responsive element at position 3434 is possibly associated with hypertension.

BACKGROUND/AIMS: Several polymorphisms of vasoactive hormones have been implicated in hypertension. Erythropoietin (EPO) interacts with vasoactive substances, such as angiotensin II. Previously detected single nucleotide polymorphisms in the hypoxia-responsive element of EPO might be associated with hypertension and hypertensive end organ damages. METHODS: 400 hypertensive patients and 200 age- and gender-matched normotensive controls were genotyped for an EPO polymorphism [cytosine (C)/thymine (T) single nucleotide polymorphism] at position 3434. Patients were grouped according to their genotype into the CC group (CC genotype) and the CT/TT group (CT and TT genotype). BP was measured by ambulatory BP monitoring. RESULTS: The CC genotype was present in 87% of hypertensive patients and in 78.5% of controls (p = 0.007). In addition, patients with the CC genotype had higher BP levels compared with CT/TT genotypes (BPsys 143.7 ± 20.4 vs. 136.1 ± 13.5 mm Hg, p = 0.01, and BPdias 85.8 ± 11.6 vs. 82.4 ± 8.9, p = 0.043) despite a nearly identical number of antihypertensive drugs (2.3 ± 1.5 vs. 2.3 ± 1.6; p = 0.257). 100% of the small number of patients with end-stage renal disease (n = 15) had the CC genotype. CONCLUSION: The CC genotype of the EPO gene at position 3434 is more frequently found in patients with hypertension and is associated with higher BP levels.

Dosing strategies for conversion of haemodialysis patients from short-acting erythropoiesis stimulating agents to once-monthly C.E.R.A.: experience from the MIRACEL study.

AIMS: To analyse the impact of dosing decisions for continuous erythropoietin receptor activator (C.E.R.A.), a continuous erythropoietin receptor activator. METHODS: This was a prospective, multicentre, single-arm study in haemodialysis patients receiving epoetin alfa/beta or darbepoetin alfa. After a 2-month screening phase, patients were converted to monthly C.E.R.A. using pre-filled syringes during a 5-month titration phase and a 2-month evaluation phase. RESULTS: Four hundred and twenty-four eligible patients were converted to C.E.R.A. Mean Hb were 11.7 ± 0.7, 11.7 ± 0.8 and 11.5 ± 0.8 g/dl during screening, titration and evaluation, respectively. C.E.R.A. starting dose was 125 µg (n = 311) or 200 µg (n = 106), with corresponding final doses of 129 ± 61 µg and 203 ± 58 µg. The mean number of C.E.R.A. dose decreases and increases were 0.9 ± 1.0 and 1.1 ± 1.0 per patient, respectively. Hb rarely exceeded 12.5 g/dl after a C.E.R.A. dose increase (< 8%) and remained ≥ 11 g/dl after a dose reduction on approximately three-quarters of occasions. Among the 53 occasions where Hb decreased ≥ 2 g/dl between two consecutive visits, the previous dose had been withheld (n = 9), concomitant blood loss, coagulopathy or infection was present (n = 13), or iron parameters were low (n = 17). There were 104 adverse events/month during screening, and 45/month during the titration/evaluation phases. Serious adverse events occurred in 18.0 and 21.0 patients/month during the screening and titration/evaluation phases, respectively. CONCLUSION: Switching haemodialysis patients from shorter-acting ESA to once-monthly C.E.R.A. using pre-filled syringes is straightforward, and Hb levels remain stable. Starting dose recommendations and dose changes correlated well with the clinical setting. Collateral factors such as infection or aggravating concomitant medical conditions should be taken into account.

[Effects of LDL-apheresis--more than reduction of cholesterol?]. / Effekte der LDL-Apherese--Mehr als nur Cholesterinsenkung?

LDL apheresis is a safe and very effective extracorporeal treatment of refractory hypercholesterolemia. LDL cholesterol levels can be reduced with this procedure by more than 60%. C-reactive protein (CRP) is a known marker of inflammation in atherosclerosis. Interestingly CRP can be effectively removed by a single LDL apheresis, but further studies are needed to substantiate the effect of extracorporeal reduction of CRP on the progression of atherosclerosis. However, adhesion molecules and activities of inflammatory cells were also found to be reduced after a single LDL apheresis. The biochemical composition of newly formed LDL particles after apheresis is altered: LDL particles isolated after LDL apheresis had an increased resistance to oxidative stress in vitro. In addition, antioxidants are not depleted by LDL apheresis. The extracorporal method itself does not have a negative impact on the oxidative/antioxidative balance. A recent investigation showed that LDL-cholesterol had a more pronounced effect on blood rheology than fibrinogen. This observation may explain why a single LDL apheresis leads to better myocardial perfusion, as demonstrated by PET in patients with hypercholesterolemia. These additional effects have so far only been known with statins. Further investigations are needed to substantiate the observed potentially beneficial effects of LDLapheresis beyond its effect of lowering LDL.

Impact of anal incontinence on psychosocial function and health-related quality of life.

The relationship among the frequency of anal incontinence (AI), psychosocial factors, and health-related quality of life (HRQOL) was evaluated. Consecutive patients (n=280) completed a bowel symptom questionnaire, the Symptom Checklist 90 -- Revised (SCL 90-R), and an assessment of HRQOL. Group 1 had no incontinence, Group 2 had AI less than once per week, and Group 3 experienced AI more than once per week. Multivariate analyses were used to evaluate the relationship among symptoms, the SCL-90-R subscales, and HRQOL. Group 3 reported more frequent stools than the other groups. Significant psychological distress was present in both incontinent groups compared to Group 1 (P=0.002). A reduction in overall HRQOL was also seen in the incontinent groups. Depression was inversely correlated with QOL-Satisfaction and QOL-Ratings and positively correlated with QOL-Interference. AI was associated with impaired psychosocial function and decreased HRQOL. The frequency of AI was associated with increased HRQOL-Interference, but minimally with the degree of psychosocial impairment.

The effects of tegaserod, a 5-HT receptor agonist, on gastric emptying in a murine model of diabetes mellitus.

UNLABELLED: The C57BLKS/J db/db transgenic mouse is a model of diabetes mellitus that has been shown to have delayed gastric emptying. We assessed gastric emptying rates in C57BLKS/J mice, and determined the effects of tegaserod, a new selective 5-HT(4) receptor partial agonist, on gastric emptying. METHODS: Gastric emptying rates of a 20% glucose test meal were determined in 12-20-week-old female db/db mice and control littermates. The effects of tegaserod (0.1-2.0 mg kg(-1), i.p.) on gastric transit were tested in a second group of db/db mice. Pretreatment with GR11308, a specific 5-HT(4)antagonist, was used to confirm the mechanism of action of tegaserod on gastric emptying. RESULTS: Gastric emptying of glucose was significantly slower in db/db mice than in control littermates. Tegaserod (0.1 mg kg(-1)) significantly accelerated the gastric emptying rate of glucose in db/db mice, reducing the fraction of the meal remaining in the stomach at 30 min by 80%. GR11308 blocked the gastrokinetic effects of tegaserod. CONCLUSIONS: Gastric emptying was impaired in db/db mice. Low dose tegaserod improved gastric emptying rates in this model of gastroparesis through the activation of 5-HT(4) receptors. These findings suggest that 5-HT(4) receptor agonists may prove useful for improving delayed gastric emptying in gastroparesis.

Subtypes of anal incontinence associated with bowel dysfunction: clinical, physiologic, and psychosocial characterization.

BACKGROUND: We hypothesized that functional anal incontinence with no structural explanation comprises distinct pathophysiologic subgroups that could be identified on the basis of the predominant presenting bowel pattern. METHODS: Consecutive patients (n = 80) were prospectively grouped by bowel symptoms as 1) incontinence only, 2) incontinence + constipation, 3) incontinence + diarrhea, and 4) incontinence + alternating bowel symptoms. The Hopkins Bowel Symptom Questionnaire, the Symptom Checklist 90-R, and anorectal manometry were completed. RESULTS: Significant group differences were found between subcategories of incontinent patients on the basis of symptoms. Abdominal pain was more frequent in patients with altered bowel patterns. Patients with alternating symptoms reported the highest prevalence of abdominal pain, rectal pain, and bloating. Basal anal pressures were significantly higher in alternating patients (P = 0.03). Contractile pressures in the distal anal canal were diminished in the incontinent-only and diarrhea groups (P = 0.004). Constipated patients with incontinence exhibited elevated thresholds for the urge to defecate (P = 0.027). Dyssynergia was significantly more frequent in patients with incontinence and constipation or alternating bowel patterns. CONCLUSIONS: Distinct patterns of pelvic floor dysfunction were identified in patient subgroups with anal incontinence, based on the presence or absence of altered bowel patterns. Physiologic assessments suggested different pathophysiologic mechanisms among the subgroups. The evaluation of patients with fecal incontinence should consider altered bowel function.

Antidepressants in the treatment of irritable bowel syndrome and visceral pain syndromes.

Irritable bowel syndrome (IBS) is characterized by abdominal pain associated with disordered defecation, which may include urgency and altered stool frequency. Visceral pain syndromes, including IBS, may be effectively treated by a variety of therapies that modulate the interactions between the central and enteric nervous systems. Clinical observations and preliminary data suggest that antidepressants may be efficacious for the treatment of these syndromes. The tricyclic antidepressants (TCAs) have been utilized most extensively in this area, but there is a need for more rigorous efficacy data. Serotonin, an important neurotransmitter in both the central and enteric nervous systems, modifies both motility and sensation in the gut. Recognition of the importance of serotonin in digestive motility and sensation has sparked interest in the use of agents that modify serotonergic transmission in visceral pain syndromes. Pharmacological therapeutics that modulate the biological amines (serotonin, norepinephrine, dopamine and catecholamines) both peripherally and within the central nervous system may offer more effective therapies for these disorders. The selective serotonin reuptake inhibitors are commonly used in clinical practice, but more rigorous, controlled studies are needed to determine their effects beyond the treatment of psychiatric comorbidity. The newer generation antidepressants may provide additional insight into the pathophysiology of the brain-gut interactions and their relationship to functional bowel disorders, providing new therapeutic interventions.

No acute impact of lipid apheresis treatment on free radical scavenging enzyme gene expression in white blood cells.

BACKGROUND: Lipid apheresis (LA) treatment has been suggested to cause oxidative stress. Defense against oxygen-radical-mediated damage is provided by nonenzymatic and enzymatic antioxidants. In the present investigation we have investigated whether gene expression of free radical scavenging enzymes (FRSE) is affected in leukocytes of patients undergoing LDL-apheresis. MATERIALS AND METHODS: For this purpose cellular glutathione peroxidase (GPx-1), phospholipid glutathione peroxidase (GPx-4), glutathione reductase (GSSG-R), glutathione synthetase (GSH-S), Cu/Zn-superoxide dismutase (SOD-1) and catalase (CAT) mRNA expression were followed at the start (SA) and immediately after (EA) LA treatment (n = 25). Gene expression was determined by quantitative RT-PCR with the LightCycler(R) instrument (Roche Diagnostics, Mannheim, Germany) and transcription elongation factor-2 as reference gene. RESULTS: The expression of GPx-1, GPx-4, GSSG-R, GSH-S, SOD-1, CAT mRNA was not affected by a single LA treatment. Free radical scavenging enzymes mRNAs were significantly (P < 0.05) increased in the LA patients (GPx-1: 2.00 +/- 1.37; GPx-4: 0.52 +/- 0.46; GSSG-R: 0.07 +/- 0.03; GSH-S: 0.04 +/- 0.03; SOD-1: 1.12 +/- 0.74; CAT: 0.15 +/- 0.07) when compared with 26 healthy blood donors (GPx-1: 1.1 +/- 0.6; GPx-4: 0.35 +/- 0.19; GSSG-R: 0.02 +/- 0.01; GSH-S: 0.03 +/- 0.01; SOD-1: 0.16 +/- 0.08; CAT: 0.09 +/- 0.05; mean +/- SD). CONCLUSIONS: These results show that the LA procedure does not acutely affect the antioxidant defense system on the gene level but suggests that the chronic stress resulting from hyperlipidaemia and/or LA may cause FRSE gene induction.

No acute impact of haemodialysis treatment on free radical scavenging enzyme gene expression in white blood cells.

OBJECTIVE: Oxidative stress has been implicated in the side-effects caused by haemodialysis (HD) treatment. DESIGN: In the present study we have investigated whether gene expression of the enzymatic defence system provided by cellular glutathione peroxidase (GPx-1), phospholipid glutathione peroxidase (GPx-4), glutathione reductase (GSSG-R), glutathione synthethase (GSH-S), Cu/Zn-superoxide dismutase (SOD-1) and catalase (CAT) is affected by HD. The GPx-1, GPx-4, GSSG-R, GSH-S, SOD-1 and CAT mRNA were determined in white blood cells by quantitative reverse transcriptase-polymerase chain reaction with the LightCycler instrument and transcription elongation factor-2 as reference gene at the start (SD) and immediately after (ED) dialysis treatment (n = 36). In a subgroup (n = 10), messenger RNA (mRNA) expression was determined hourly during a 5 h HD. RESULTS: The expression of GPx-1, GPx-4, GSSG-R, GSH-S, SOD-1 and CAT mRNA was not affected by a single HD treatment. All mRNAs were significantly (P < 0.05) increased in HD patients [median (16. percentiles (perc.); 84. perc.)]: GPx-1: 2.18 (0.89; 3.23); GPx-4: 0.41 (0.26; 0.74); GSSG-R: 0.04 (0.02; 0.10); GSH-S: 0.04 (0.02; 0.08); SOD-1: 0.32 (0.20; 0.62); CAT: 0.12 (0.06; 0.18) when compared with healthy blood donors (GPx-1: 0.91 (0.60; 1.44); GPx-4: 0.27 (0.16; 0.43); GSSG-R: 0.02 (0.01; 0.02); GSH-S: 0.02 (0.02; 0.04); SOD-1: 0.15 (0.10; 0.18); CAT: 0.07 (0.04; 0.16). CONCLUSIONS: These results show that the HD procedure does not acutely affect the antioxidant defence system on the gene level but suggest that the chronic stress caused by uraemia and/or HD may cause gene induction of the enzymatic defence system.

First steps toward the establishment of a German low-density lipoprotein-apheresis registry: recommendations for the indication and for quality management.

New recommendations for the indication of treatment with selective extracorporeal plasma therapy low-density lipoprotein apheresis (LDL-apheresis) in the prevention of coronary heart disease are urgently needed. The following points are the first results of the ongoing discussion process for indications for LDL-apheresis in Germany: all patients with homozygous familial hypercholesterolemia with functional or genetically determined lack or dysfunction of LDL receptors and plasma LDL cholesterol levels >13.0 mmol/L (>500 mg/dL); patients with coronary heart disease (CHD) documented by clinical symptoms and imaging procedures in which over a period of at least 3 months the plasma LDL cholesterol levels cannot be lowered below 3.3 mmol/L (130 mg/dL) by a generally accepted, maximal drug-induced and documented therapy in combination with a cholesterol-lowering diet; and patients with progression of their CHD documented by clinical symptoms and imaging procedures and repeated plasma Lp(a) levels >60 mg/dL, even if the plasma LDL cholesterol levels are lower than 3.3 mmol/L (130 mg/dL). Respective goals for LDL cholesterol concentrations for high-risk patients have been recently defined by various international societies. To safely put into practice the recommendations for LDL-apheresis previously mentioned, standardized treatment guidelines for LDL-apheresis need to be established in Germany that should be supervised by an appropriate registry.

Polarized function of thick ascending limbs of Henle cells in osmoregulation.

BACKGROUND: Organic osmolytes are necessary for osmoregulation in mammalian kidney. Since renal epithelial cells in many cases possess specific mechanisms both for uptake and osmotically regulated release, we investigated their localization in polarized cells. METHODS: An immortalized epithelial cell line derived from the thick ascending limb of Henle's loop (TALH) was used to examine the transport characteristics of the apical and basolateral plasma membranes for osmotic regulation of organic osmolytes. Cells were cultured on filters in a two-compartment chamber. RESULTS: In culture under hypertonic conditions the TALH cells accumulated in the following balance: sorbitoverline> betaine = myo-inositoverline> glycerophosphoryl choline (GPC). When extracellular osmolarity was decreased, then sorbitol was released on the apical side, whereas betaine and myo-inositol efflux occurred on the basolateral side. GPC release showed no preference of either side. Taurine did not seem to be necessary for osmoregulation under these conditions. Osmotically regulated myo-inositol and betaine uptake was located on the apical side, and choline uptake took place on both sides equally. CONCLUSION: These results show that in renal epithelial cells, both osmotically induced release and the uptake of organic osmolytes are divided between the apical and the basolateral sides. This might be important for volume regulation.