High dose of L-carnitine increases platelet aggregation and plasma triglyceride levels in uremic patients on hemodialysis

Uremic patients undergoing chronic hemodialysis demonstrate a secondary systemic carnitine deficiency. We studied the effect of carnitine replacement with high doses (L-carnitine, 3 g/day) similar to those used in the treatment of primary systemic carnitine deficiency. 10 uremic patients on hemodialysis were randomly selected into a control group (4 patients) treated by placebo and a treatment group (6 patients) treated by L-carnitine. Plasma lipoprotein concentration and composition as well as platelet aggregation were studied before and after treatment. Following carnitine administration, a paradoxical rise in plasma triglyceride concentration from 180 +/- 66 to 219 +/- 88 mg% (p less than 0.05) was noted. No other significant changes in lipoprotein concentration and composition or in plasma apoprotein A-I and B concentration were observed. Carnitine treatment caused a significant rise in platelet aggregation induced by epinephrine, ADP, and thrombin. These findings suggest a harmful effect of L-carnitine replacement therapy when given in high doses, causing aggravation of uremic hypertriglyceridemia and increased platelet aggregation in patients predisposed to thromboembolic phenomena.     

Enhanced in vitro platelet aggregation in hemodialysis patients

Hemodialysis patients suffer from premature atherosclerosis and various thrombotic and thromboembolic phenomena. Despite enhanced in vivo platelet activity, it is unclear whether in vitro platelet aggregation is increased or reduced in this population. We studied platelet aggregation in response to adenosine diphosphate and to epinephrine in 20 chronic hemodialysis patients and 21 controls. In the patient group the in vitro platelet aggregation was significantly enhanced in response to both aggregating agents. Our study demonstrated that in vitro platelet aggregation is enhanced in patients with chronic renal failure undergoing hemodialysis.     

高通量血液透析联合左卡尼汀对尿毒症心肌病的临床研究

目的 高通量血液透析联合左卡尼汀对尿毒症心肌病的影响.方法 选取81例于本院门诊和住院部透析的患者,随机分成两组:实验组41例,对照组40例,所有患者均每周3次血液透析,每次4h,实验组自2012年10月开始接受高通量血液透析联合左卡尼汀治疗,对照组进行单纯的高通量血液透析治疗,两组患者都观察8个月.治疗前后检测血红蛋白、血细胞比容,做常规超声心动图,观察左心室舒张期末内径(LVIDd)、左心室收缩末期内径(LVIDs)、室间隔舒张期末期厚度(IVSd)、左室心肌质量(LVM)、左室心肌质量指数(LVMI)、左室后壁厚度(PWTH)、射血分数(EF)、左心室的舒张功能(EPSS)等.结果 治疗8个月后,实验组患者的血红蛋白、血细胞比容与对照组比较明显升高(P＜0.05),超声心动图EF值明显升高,LVIDd、LVIDs、IVSd、PWTH、LVM、LVMI明显降低,差异均有统计学意义(P＜0.05).结论 高通量血液透析联合左卡尼汀在改善尿毒症心肌病患者心肌重构及心功能方面有较好的疗效.     

血液透析对尿毒症患者血小板功能及膜糖蛋白的影响

观察血液透析对尿毒症患者血小板功能、血小板膜糖蛋白（ＧＰ）的影响并探讨其作用机理。方法应用血小板聚集仪和流式细胞仪观察尿毒症患者血液透析前后，血小板聚集功能和血小板膜糖蛋白的变化。结果血液透析前，尿毒症组的血小板聚集率明显低于正常对照组；其血小板膜糖蛋白Ⅰｂ、Ⅱｂ／Ⅲａ量与对照组相比无明显差异。血液透析后，患者血小板聚集率无明显增加，但其血小板膜ＧＰⅠｂ、ＧＰⅡｂ／Ⅲａ量明显增高。血液透析前后，以ＡＤＰ活化血小板，患者血小板表达的ＧＰⅡｂ／Ⅲａ量与对照组相比无显著性差异。结论血液透析不能改善尿毒症患者血小板功能。血液透析可使血小板活化，导致其膜糖蛋白升高。     

L-carnitine substitution in patients on chronic hemodialysis

Patients on chronic hemodialysis with hyperlipidemia were found to respond either with decreased levels (responders) or with a further increase of the plasma triglyceride levels (nonresponders) to a carnitine substitution therapy. The aim of the present study was to find possible predictors to distinguish between responders and nonresponders prior to the initiation of therapy. Since it is suggested that erythrocytes are involved in carnitine transport to tissues, it was of interest to determine plasma and erythrocyte carnitine concentrations in the hemodialyzed patients before and during carnitine substitution therapy and to compare the results with those of healthy controls. Before therapy, comparatively lower plasma levels of both free and total carnitine, but higher portions of short-chain acylcarnitine on total carnitine were found in all patients. In erythrocytes, the nonresponders showed significantly higher total carnitine levels, compared to responders and controls. After the start of carnitine substitution, the increase of total plasma carnitine during the substitution period corresponded with the carnitine dose administered in responders, in nonresponders the highest carnitine values were found in the second week when the lower carnitine dose was administered. The changes of the plasma short-chain acylcarnitine levels with time were very similar to those of plasma triglycerides. All patients showed a time-delayed accumulation of carnitine in erythrocytes and, interestingly, markedly higher concentrations in the second week when the lower carnitine dose was administered. The results of the present study demonstrate that the erythrocyte carnitine content is a reliable predictor to distinguish between responders and nonresponders prior to the start of a carnitine substitution therapy.     

Osteoprotegerin and uremic osteoporosis in chronic hemodialysis patients

International Urology and Nephrology - Osteoprotegerin (OPG) is a powerful inhibitor of osteoclast activity, and it plays an important role in bone metabolism. In hemodialysis (HD) patients, the...     

Effect of L-carnitine supplementation in hemodialysis patients.

BACKGROUND/AIM: L-Carnitine is important in beta-oxidation of fatty acids. A lack of carnitine in hemodialysis patients is caused by insufficient carnitine synthesis and especially by its loss during dialysis. The aim of our study was to test the influence of carnitine supplementation on plasma lipids, red blood cell count, and metabolism of free radicals. METHODS: Twelve regularly dialyzed patients (average age 55.5 years, average dialysis treatment period 22.5 months) were given 15 mg/kg L-carnitine intravenously three times weekly (after each hemodialysis session) for 6 months. Laboratory markers of oxidative stress, lipid metabolism, and red blood cell count were measured before the supplementation and then controlled during two 3-month intervals. Nine patients were retested 3 months after the supplementation had ended. RESULTS: All supplemented patients showed increased plasma free carnitine in comparison with the pretreatment values (113.3 +/- 11.2 vs. 62.3 +/- 16.7 micromol/l, p < 0.001). The proportion of decreased L-carnitine values after hemodialysis was reduced from 79 to 22%. Plasma total cholesterol (4.66 +/- 0.30 mmol/l after treatment vs. 5.65 +/- 1.53 mmol/l before treatment, p < 0.05) and LDL cholesterol (1.74 +/- 0.86 vs. 2.81 +/- 1.43 mmol/l, p < 0.05) decreased. The albumin concentration significantly increased from 34.8 +/- 7.3 to 46.0 +/-5.4 g/l (p < 0.05). Intraerythrocyte reduced glutathione increased from 1.65 +/- 0.25 to 2.23 +/- 0.16 mmol/l (p < 0.001), and the plasma antioxidant capacity increased from 1.65 +/- 0.09 to 2.06 +/- 0.17 mmol/l (p < 0.001). At the same time, plasma malondialdehyde decreased from 4.18 +/- 0.72 to 3.07 +/- 0.35 micromol/l (p < 0.001). The erythropoietin dose could be reduced from an average value of 5,500 to 3,500 U/week. No significant changes in the above-mentioned parameters were observed in a control group of dialyzed patients without L-carnitine supplementation. CONCLUSION: Regular carnitine supplementation of hemodialysis patients can improve their lipid metabolism, protein nutrition, red blood cell count, and antioxidant status.     

尿毒症血液透析患者乳酸脱氢酶水平变化

目的 探讨尿毒症血液透析患者乳酸脱氢酶变化及其临床意义.方法 纳入尿毒症未透析者、尿毒症透析者及正常健康人各15例,采用全自动生化分析仪分别检测血清血红蛋白、肌酐、尿素氮及乳酸脱氢酶水平.结果 尿毒症未透析患者血清乳酸脱氢酶水平较正常健康人明显升高(P＜0.05);尿毒症血液透析组患者透析后乳酸脱氢酶水平与透析前相比有升高,但差异无统计学意义(P＞0.05).结论 尿毒症未透析患者体内乳酸脱氢酶水平的升高无器官特异性,血液透析改变了尿毒症患者体内乳酸脱氢酶环境,乳酸脱氢酶有可能作为评价血液透析充分性的观察指标.     

Enhanced platelet apoptosis in chronic uremic patients

Background: There is a paucity of research on platelet apoptosis and its contribution to platelet dysfunction in uremic patients. The present study sought to analyze platelets apoptosis in uremic patients who underwent different dialysis modalities. Methods: Sixteen chronic uremic patients (5 on hemodialysis, 6 on peritoneal dialysis and 5 on non-dialysis) and 16 controls were studied. Platelet-rich plasma was detected for apoptotic events including depolarization of mitochondrial inner membrane potential (ΔΨm), phosphatidylserine (PS) exposure, activation of caspases-3 and Bcl-2 family proteins variations by Flow Cytometry or by Western-Blot. Washed normal platelets were incubated with normal or uremic platelet poor plasma and then were detected apoptotic events. Platelets function was assessed by ristocetin induced aggregative function test. Results: Compared to controls, uremic platelets demonstrated greater apoptosis for the ΔΨm depolarization (43.48?±?9.58 vs. 52.76?±?15.36, p?=?0.005) as well as PS exposure (1.36?±?0.51 vs. 0.99?±?0.27, p?0.001). There was no significant difference among different treatment groups (for the ΔΨm depolarization f?=?0.16, p?=?0.85; for the PS exposure f?=?1.06, p?=?0.36). Western Blot analyses showed caspase-3 activation and pro-apoptotic Bcl-2 family proteins expression. Platelets exposed to uremic plasma exhibited distinct apoptosis phenomena. Ristocetin induced platelet aggregation was markedly diminished in uremic patients and treated platelets. Conclusions: These findings indicate that platelets are incurred apoptosis in uremia patients. Uremic plasma accelerates apoptosis of normal platelets, resulting in a dysfunctional pattern of platelets in uremia. Uremic platelets apoptosis has no relationship with dialysis modality.     

血液透析病人皮肤瘙痒的研究进展

皮肤瘙痒是血液透析病人常见的合并症之一,其机制不甚明确,目前认为和肥大细胞、内源性阿片物质、皮肤干燥症、继发性甲状旁腺功能亢进、炎症和周围神经病变等相关。血液透析病人皮肤瘙痒的治疗分为局部治疗和全身治疗,包括紫外线光疗、皮肤软化剂、抗组胺药、辣椒碱、加巴喷丁等,但疗效都欠佳,需开展进一步的研究。     

Serum paraoxonase activity in uremic predialysis and hemodialysis patients

BACKGROUND: Paraoxonase (PON1) is a high-density lipoprotein (HDL)-associated enzyme and has been shown to reduce the susceptibility of low-density lipoprotein (LDL) to lipid peroxidation. This study aimed to investigate the activity and phenotype distribution of serum paraoxonase in uremic patients, and to evaluate the correlations of uremia-associated substances (urea, creatinine (Cr) and uric acid) with paraoxonase activity. METHODS: Twenty-eight patients with chronic renal failure (CRF), 44 patients with CRF undergoing hemodialysis (HD) and 26 healthy controls were included in this study. Paraoxon or phenylacetate was used as a substrate for measuring paraoxonase and arylesterase activity, respectively. The double substrate method was used to assign phenotypes. Serum lipid parameters were determined by routine laboratory methods. RESULTS: Paraoxonase activity, HDL-cholesterol and apolipoprotein (apo) AI levels were found to be significantly lower in HD patients than in controls. However, HDL-standardized paraoxonase activity (PON activity/HDL) was not different in the HD patients compared to controls. Arylesterase activity was significantly lower in both CRF and HD patients than in controls. Paraoxonase phenotype distribution was not different among the groups according to the double substrate method. Serum paraoxonase and arylesterase activities correlated inversely with serum urea and Cr levels. CONCLUSION: Patients on long-term HD have reduced paraoxonase/arylesterase activities and this could be related to reduced HDL-cholesterol and apo AI levels, as well as increased urea and Cr levels in uremia.     

Intraocular pressure in uremic patients on chronic hemodialysis

Intraocular pressure (IOP) was measured before and after hemodialysis in 30 uremic patients receiving regular treatment. Osmolality, blood pressure and weight before and after dialysis were also determined. Low IOP of 11.4 +/- 2.7 and 11.5 +/- 3.1 mm Hg was found in the left and right eye, respectively. Following hemodialysis osmolality, blood pressure and body weight decreased significantly but IOP did not rise significantly. This study suggests that there is only a remote possibility for severe IOP increase following hemodialysis in uremic patients on chronic treatment.     

Pulmonary function in uremic patients on long-term hemodialysis

Twenty patients with end-stage renal failure who were on maintenance hemodialysis (HD) underwent pulmonary function testing (PFT) before and shortly after an HD session. On pre-HD PFT, the mean values of all parameters except residual volume (RV) were in the normal range. Mean RV was high (152.9%), and mean diffusing capacity of the lung for carbon monoxide (DLCO) was high-normal (110.4%). The pre-HD static inspiratory (PImax) and expiratory pressures (PEmax) were much lower than normal (67.4% and 36.3%, respectively). After the HD session, repeat PFT revealed a small increase in expiratory flow rates, and a significant drop in PImax. There was a strong correlation between PImax and PEmax (r=0.567, p<0.01) at the pre- and post-HD stages, indicating that common mechanism(s) are responsible for impairment of both inspiratory and expiratory muscle strength. The well-preserved DLCO was thought to be due to the use of biocompatible dialyzer membranes. Chronic vascular congestion might be the other explanation of high DLCO.     

Survival of hemodialysis patients and uremic toxin removal

Uremic toxin removal based on diffusion and/or convection allows eliminating solutes with negative metabolic impact. Uremic solutes can be classified as small and water-soluble compounds, larger "middle" molecules, or protein bound solutes. The question arises whether more removal of each of these solute classes affects patient survival. Kt/V of urea is currently used as a surrogate for small water-soluble solute removal. There is ample evidence that Kt/V and survival are correlated, but the threshold Kt/V remains a matter of debate. Probably, the actually proposed threshold of 1.2 is too low. This impact of Kt/V is in contradiction with the low toxicity of urea and points to a role for other water-soluble solutes, e.g., potassium. More removal of middle molecules results in a lower morbidity and also in a lower mortality. In addition, a relationship has been demonstrated between the use of membranes with large pore size and a decrease of inflammatory status, by itself an important factor related to mortality. One of the problems is that large pore membranes are at the same time more biocompatible and reflect more dialysate impurities, compared to many small pore membranes, whereas they also reflect more dialysate impurities. It remains uncertain which one of these factors, if any, has a predominant effect. Recent studies point to a separate effect of pore size but await confirmation. Protein bound toxins inhibit several biochemical functions. Their removal pattern is totally different from that of classical markers such as urea. In analogy with drugs, it is essentially the free unbound fraction that exerts biological action; this free fraction is inversely related to serum albumin, another inflammatory marker related to survival. In a final section of this presentation, attention will be drawn to the relationship in uremic patients between inflammation, malnutrition, cardiovascular disease, and mortality, and some of the potential culprits are discussed. Virtually all of these molecules have a high molecular weight or are protein bound. It is concluded that both small and middle molecule removal have an impact on survival, so that more than urea removal alone should be pursued.     

Male hypogonadism of uremic patients on hemodialysis

Primary hypogonadism occurring among uremic men on hemodialysis has been widely investigated, yet few data are available concerning the general pattern of steroidogenesis. In 161 hemodialysis patients and in 83 healthy subjects, serum levels of gonadotropins (LH and FSH), prolactin (PRL), testosterone (T), androstenedione (A), estrone (E1), estradiol (E2), and dehydroepiandrosterone-sulphate (DHEA-S) were assessed through RIA methods. Mean +/- SD hormone levels were: LH 45.6 +/- 41.1 mIU/ml, FSH 16.3 +/- 16 mIU/ml, PRL 42.4 +/- 69.1 ng/ml, A 0.83 +/- 0.27 ng/ml, E1 64.3 +/- 31.7 pg/ml, all higher than controls; T 289 +/- 125 ng/100 ml, E2 11.8 +/- 3 pg/ml, and DHEA-S 1.4 +/- 1.4 micrograms/ml, all lower than controls. The A/T and E1/E2 ratios were also higher than controls and showed a good positive linear correlation (r = 0.40; p less than 0.001) between each other. The uremic damage acts at the testis level, impairing the activity of the enzyme 17-beta-hydroxysteroid-dehydrogenase (17-OHSD), even if a derangement of the peripheral interconversion between steroids cannot be excluded.     

Inflammatory markers and platelet aggregation tests as predictors of hemoglobin and endogenous erythropoietin levels in hemodialysis patients

BACKGROUND/AIMS: Chronic inflammation is a common cause of severe anemia and hyporesponsiveness to recombinant erythropoietin (EPO) therapy in maintenance hemodialysis (HD) patients. We compared various acute-phase markers and ex vivo platelet aggregation tests in relation to clinical conditions in order to find factors predictive of hemoglobin (Hb) and endogenous EPO levels in a cross-section of clinically stable HD patients. METHODS: In 100 subjects, pre-HD blood levels of C-reactive protein (CRP), alpha(1)-acid-glycoprotein (AGP), alpha(1)-antitrypsin (AT), immunoglobulin (Ig) M and G (by nephelometry), antigens of endothelial von Willebrand factor (vWF), type 1 plasminogen activator inhibitor and thrombomodulin, interleukin-6, lipoprotein(a) [Lp(a)] and EPO (by ELISA), and albumin, fibrinogen, iron metabolism indices, thyroid-stimulating hormone, phosphorus, parathormone, total cholesterol, triglycerides, viral hepatitis B/C markers, liver enzyme, and aluminium were determined. Platelet aggregations in response to ristocetin (RIPA), adenosine diphosphate, and collagen were measured in whole blood (electric impedance method) and platelet-rich plasma (optical aggregometry). RESULTS: Hb levels inversely correlated with IgM, Lp(a), soluble vWF antigen, phosphorus, and all platelet aggregations in whole blood, but not in platelet-rich plasma. HD duration and triglycerides were positive correlates of anemia. In a multivariable analysis, increased IgM, short HD duration, increased Lp(a) and enhanced whole blood RIPA (in descending order of significance) were independent predictors of low Hb levels. In 51 patients not treated with recombinant EPO, serum levels of this hormone inversely correlated with whole blood RIPA, AT, age, vWF antigen, AGP, and positively with viral hepatitis marker. Anemia and EPO levels were not affected by gender, body mass index, cause of renal failure, residual renal function, HD dose, protein catabolic rate, use of different heparins or dialysate buffers, ACE inhibitor therapy, and parathyroid or thyroid function. In additional 10 patients, single HD session resulted in an increase in IgM levels associated with a fall in total lymphocyte counts. CONCLUSION: Subclinical inflammation is an important determinant of anemia in maintenance HD patients. Increased serum IgM reflecting a microinflammatory effect of HD procedures, enhanced whole blood RIPA as a surrogate of vascular endothelial damage, and Lp(a) as its promoter could be markers of such impaired erythropoiesis.     

Changes in insulin binding during hemodialysis in uremic patients

To investigate factors responsible for altered insulin sensitivity in uremia, we studied 125I-insulin binding to erythrocytes in 20 uremic patients before and after dialysis. In uremic patients, predialysis binding was 50% lower in comparison with healthy controls (4.35 +/- 1.79 vs. 9.37 +/- 1.30%; p less than 0.01). Five-hour dialysis treatment resulted in a rapid increase in binding (on average to 55%; p less than 0.01). During the course of dialysis, binding to erythrocytes from 2 selected patients steadily increased in a time-dependent manner (on average 24%/h). The dialysis-induced increase in binding did not correlate with the changes in plasma insulin levels, but depended on the efficiency of dialysis as assessed by a relative decrease in plasma urea and creatinine. After an intravenous glucose load, the insulin-to-glucose ratio decreased in parallel with the increase in binding after dialysis. The results indicate that uremic plasma contains dialyzable substances which reversibly inhibit insulin binding, leading to altered insulin sensitivity.     

透析中心夜间血液透析治疗尿毒症患者的疗效及安全性

目的 观察透析中心夜间血液透析（INHD）治疗尿毒症患者的疗效和安全性。 方法 32例维持性血液透析（MHD）患者行INHD共6个月,3次/周,7.5 h/次。进入INHD前及开始后1、3、6（或3、6）个月测定透析相关指标,做心脏彩超检查、SF-36问卷调查,记录药物使用情况。 结果 进入INHD后,患者透前血压显著下降（130.3/86.0比139.3/88.6 mm Hg, P < 0.01）;透后血压显著上升（121.1/80.5比115.0/77.8 mm Hg,P < 0.01）;透析中高血压（9.8%比24.0%）及低血压发生率（7.3%比14.9%）均显著减少（均P < 0.01）。INHD 6个月后血磷[（1.37±0.27）比（2.08±0.49） mmol/L,P < 0.01]和iPTH值[（355.4±139.6）比（632.3±750.0） ng/L,P < 0.01]显著下降;血钙水平显著上升[（2.64±0.25）比（2.28±0.37） mmol/L,P < 0.05]。与INHD 1个月相比,INHD 6个月时高密度脂蛋白（HDL）显著升高[（1.27±0.29）比（0.75±0.08） mmol/L];低密度脂蛋白（LDL）显著下降[（2.04±0.52）比（2.75±0.75） mmol/L,P < 0.05];尿素下降率（URR）[（79.7±0.1）%比（64.7±4.7）%]和Kt/V（1.40±0.44比0.89±0.25,P < 0.01）显著增加;β2-MG水平显著下降[（17.3±3.9）比（24.6±5.9） mg/L,P < 0.01];左室质量指数（LVMI）显著下降（99.8±29.0比114.8±72.7,P < 0.05）;SF-36量表生理功能、生理职能和情感职能得分显著升高（均P < 0.01）。INHD 6个月时降压药物使用种类、EPO剂量、活性维生素D3（P < 0.05）及降磷药物剂量（P < 0.01）均显著减少,停用降压药、活性维生素D3及降磷药物患者数显著增加（P < 0.05）。 结论 INHD能改善高血压、贫血、钙磷代谢、脂质代谢紊乱,改善心功能,提高生活质量,不良反应少,具有很好的应用前景。