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.     

Effect of oral carnitine supplementation on disturbances of lipid metabolism in the uremic rat

Carnitine deficiency has recently been incriminated in the pathogenesis of the disturbed lipid metabolism observed in hemodialysis patients. The present study was performed to investigate the effects of L-carnitine administration on the lipid metabolism of rats with experimental chronic renal failure as compared to normal rats. Three groups of rats were studied: the first had induced chronic uremia, the second was sham-operated and pair-fed with the first, and the third was sham-operated and fed ad libitum. Serum triglycerides were significantly higher in uremic rats than in control animals of both groups. In addition to triglycerides, serum total cholesterol and phospholipids were also increased in uremic rats. The fractional clearance rate of Intralipid [K2(%)] was decreased in uremic as compared to control animals. The in vivo oxidation of radiolabeled palmitate was lower in uremic than in ad libitum-fed control animals but not lower than in pair-fed control rats. The daily oral administration of L-carnitine to uremic rats was associated with stable serum triglycerides. On the contrary, serum triglycerides increased significantly in the untreated uremic rats over the same period of time. Serum total cholesterol and phospholipids remained similar in the presence and the absence of L-carnitine treatment. The intravenous fat tolerance test of carnitine-supplemented uremic rats improved slightly, although not significantly, when compared to that of untreated uremic rats. In conclusion, oral L-carnitine supplementation in chronically uremic rats had only modest or no effects on several plasma lipid parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects

Previous studies have reported conflicting results of carnitine supplementation on plasma lipids in patients with chronic renal failure. We therefore performed a four center, double-blind placebo controlled trial to evaluate the effects of post-hemodialysis intravenous injection of L-carnitine in ESRD patients on maintenance hemodialysis. Thirty-eight patients received up to six months of L-carnitine infusions (20 mg/kg) post-dialysis and 44 patients received placebo infusions. In both groups of patients, baseline pre-dialysis plasma and red blood cell total carnitine levels were normal, but pre-dialysis plasma-free carnitine concentrations and free/total ratios were subnormal, and plasma acyl levels were elevated. Post-dialysis plasma free and total carnitine concentrations were also subnormal. Plasma and red blood cell total carnitine levels rose eightfold in carnitine recipients, but were unchanged from baseline in those receiving placebo. There were no significant changes observed in plasma triglycerides, HDL-cholesterol or other lipoprotein parameters in either the carnitine or placebo treated groups. We conclude that carnitine metabolism is altered in uremia. Furthermore, in a randomly-selected hemodialysis population, L-carnitine injection at the dose of 20 mg/kg results in significant increases in blood (and perhaps tissue) carnitine levels, but this is not associated with any major effects on lipid profiles.     

Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review

There are many causes for carnitine depletion during maintenance hemodialysis. Supplementation with L-carnitine in animals has been associated with improvement in some abnormalities also present in chronic renal failure. However, it is still controversial whether restoring plasma or tissue carnitine will correct clinical or biologic symptoms observed in maintenance hemodialysis. A systematic review is here performed to determine the effects of L-carnitine in maintenance hemodialysis patients. Eighty-three prospective trials were identified from 1978 to 1999 in which L-carnitine was randomly allocated in 21 trials. Change in serum triglycerides, cholesterol fractions, hemoglobin levels, erythropoietin dose, and other symptoms (muscle function, exercise capacity, and quality of life) were examined. A total of 482 patients in 18 trials were considered for analysis. There was no effect of L-carnitine on triglycerides, total cholesterol, or any of its fractions. Before the erythropoietin (EPO) era, L-carnitine treatment was associated with improved hemoglobin (P < 0.01) and with a decreased EPO dose (P < 0.01) and improved resistance to EPO when patients routinely received EPO. Muscle function, exercise capacity, and quality of life could not be reliably assessed because of the noncombinable nature of end points and the limited number of trials. In conclusion, L-carnitine cannot be recommended for treating the dyslipidemia of maintenance hemodialysis patients. By contrast, this review suggests a promising effect of L-carnitine on anemia management. The route of L-carnitine administration should be evaluated because there is no evidence as to the most efficient method of administration in maintenance hemodialysis.     

Pathogenic roles of post-heparin lipases in lipid abnormalities in hemodialysis patients

The relative roles of hepatic lipase and lipoprotein lipase in the pathogenesis of uremic lipid abnormalities were studied in 92 hemodialysis patients. Fasting serum cholesterol, triglyceride, and HDL-cholesterol concentrations were measured. Plasma lipoprotein electrophoretic patterns were determined in all patients. Hepatic lipase and lipoprotein lipase activities were selectively measured in post-heparin plasma in 59 patients. Hemodialysis patients had higher serum triglyceride and lower HDL-cholesterol concentrations than did their age and sex-matched control subjects. Both hepatic and lipoprotein lipase activities were reduced in hemodialysis patients. An inverse relation between lipoprotein lipase activities and serum triglyceride concentrations emerged. Lipoprotein lipase activities correlated with in vivo post-heparin fractional clearance rates of Intralipid. A positive correlation between lipoprotein lipase activities and HDL-cholesterol concentrations probably reflected impaired catabolism of triglyceride-rich lipoproteins being responsible for the low HDL-cholesterol concentrations. Hemodialysis patients (41.3%) had an abnormal lipoprotein (the 'mid-band'). While hepatic lipase activities did not correlate with any parameters of lipid metabolism, patients with 'low' hepatic lipase activities had a significantly higher prevalence of 'mid-bands' than did those with 'normal' activities. No evidence was developed to prove that the 'mid-band' lipoproteins were remnant particles.     

Effect of metabolic acidosis on hyperlipidemia in uremia

Nine patients (aged 18±1 years) on maintenance hemodialysis with metabolic acidosis and hyperlipidemia were studied before and after 2 weeks of oral sodium bicarbonate (NaHCO₃) treatment to correct the acidosis. To control for the effect of additional sodium, they were also studied after 2 weeks of an equivalent amount of oral sodium chloride (NaCl). Oral NaHCO₃ treatment led to significant increases in venous pH, serum bicarbonate, and serum 1,25-dihydroxyvitamin D₃ concentrations, but no significant change in total and ionized calcium, phosphate, sodium, potassium, creatinine, blood urea nitrogen, and intact parathyroid hormone concentrations. Oral NaCl did not change any of the biochemical parameters. Before treatment of acidosis, these uremic patients had high serum triglycerides, low serum high-density lipoprotein (HDL) cholesterol, but normal total cholesterol compared with controls. Following 2 weeks of NaHCO₃ treatment, there was a significant decrease in the serum concentrations of triglycerides (P<0.01). HDL and total cholesterol did not change. There were no changes in triglycerides, HDL or total cholesterol from baseline values following 2 weeks of NaCl. Thus treatment of metabolic acidosis ameliorated hypertriglyceridemia but had no effect on HDL and total cholesterol in patients with uremia on hemodialysis. The underlying mechanism may involve 1,25-dihydroxyvitamin D3. Received: 3 August 1998 / Revised: 30 November 1998 / Accepted: 2 December 1998     

Platelets and platelet function in patients with chronic uremia on maintenance hemodialysis.

In 20 chronic uremic patients on maintenance hemodialysis, who were not taking any medication known to affect platelet function, the following investigations were carried out: platelet count, fibrin/fibrinogen degradation products, fibrinogen and plasminogen concentration, platelet adhesiveness, clot retraction and platelet aggregation induced by ADP, ristocetin, fibrinogen, collagen and epinephrine. The only significant abnormal result was a decreased clot retraction. We consider many cases of so-called uremic bleeding to be caused by the medication taken and conclude that on well-controlled hemodialysis treatment, bleeding tendency should not be a major problem.     

Lipid Metabolism in Uremia: Effect of Regular Hemofiltration and Hemodialysis Treatment

Plasma triglycerides and cholesterol were measured in controls, non-dialyzed patients with chronic renal insufficiency and uremic patients receiving either regular hemodialysis or hemofiltration treatment. Normal and elevated cholesterol levels remained generally unaffected by chronic hemodialysis and hemofiltration as well. Whereas long-term hemodialysis even up to 59 months (home-dialysis) was unable to improve hypertriglyceridemia, patients undergoing regular hemofiltration showed a prolonged decrease in plasma triglycerides. In one case, excessive hypertriglyceridemia still existing after five years of chronic hemodialysis could be normalized by hemofiltration.     

Effects of raloxifene on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis

BACKGROUND: Premature amenorrhea and hypoestrogenism and lack of hormone replacement therapy after menopause have been frequently reported in uremic women on dialysis. Therefore, in addition to renal osteodystrophy, postmenopausal women on dialysis could be at risk of osteoporosis. In addition, these patients are at higher risk for hyperlipidemia, arteriosclerosis, and subsequent coronary heart disease and stroke. Recent evidence has suggested that hormone replacement therapy (HRT) in postmenopausal women could have several beneficial effects as well as potentially serious risks. Great efforts have been made to identify therapeutic alternatives that would have the benefits of estrogen on brain and bone without its adverse effects on breast and endometrium. In the present study, we evaluated the effect of raloxifene, a selective estrogen receptor modulator (SERM), on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis. METHODS: We performed a prospective, blind, placebo-controlled, and randomized study. Fifty postmenopausal women on chronic hemodialysis with proven severe osteopenia or osteoporosis by bone densitometry were selected. After a written informed consent, patients were randomized into two groups: 25 women on placebo and 25 women on the study drug, raloxifene hydrochloride, at a dose of 60 mg/day. In all patients, we performed a baseline bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, serum lipids (total low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol and triglycerides) and serum markers of bone resorption (pyridinoline crosslinks). BMD was reassessed after 1 year of therapy. Bone resorption markers were determined every 3 months for 1 year. RESULTS: After 1 year on raloxifene therapy, lumbar spine BMD (trabecular bone) significantly improved, whereas femoral neck BMD (cortical bone) did not change significantly. No changes in BMD were observed at trabecular or cortical sites in the placebo group. Serum pyridinoline levels showed a significant decrease after 6 months on raloxifene that persisted thereafter. Low-density lipoprotein (LDL)-cholesterol decreased significantly in the raloxifene group with no changes in serum triglycerides, total cholesterol, or HDL cholesterol. No significant side effects were observed in the raloxifene group. CONCLUSION: The study demonstrates that after one year on raloxifene, postmenopausal women on hemodialysis have a significant increase in trabecular BMD, decrease in bone resorption markers and LDL-cholesterol values, suggesting that SERMs could constitute a therapeutic alternative to improve bone metabolism and control of hyperlipidemia in these patients. The possible long-term effects of raloxifene remain to be determined.     

Altered flow properties of blood and increased plasma fibrinogen in cyclosporin-treated renal allograft recipients.

BACKGROUND: Abnormalities in blood rheology may be factors contributing to cardiovascular complications and the progression of renal failure in kidney allograft recipients. The haemorheological variables haematocrit, fibrinogen, whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency and fluidity were measured in 27 cyclosporin A (CyA)-treated patients who had received a renal graft at least 6 months previously. Their creatinine clearance was in the range of 12-92 ml/min/1.73 m2 (mean 55+/-19). The values were compared with those obtained from a control group comprising 20 healthy subjects matched according to age, sex and smoking habits. RESULTS: The haematocrit, plasma fibrinogen, whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency, body mass index (BMI), mean arterial pressure (MAP) and serum triglycerides were increased in the transplanted patients, and the serum high density lipoprotein (HDL)-cholesterol and erythrocyte fluidity decreased. The haemorheological variables were used as dependent variables in a stepwise regression analysis with age, MAP, BMI, urinary albumin excretion rate, blood CyA concentration, creatinine clearance, and serum triglycerides, cholesterol and HDL-cholesterol as independent variables. Plasma fibrinogen was positively correlated with BMI and blood CyA. The whole blood viscosity was positively correlated with blood CyA and negatively with serum HDL-cholesterol. Only serum triglycerides remained correlated with erythrocyte aggregation tendency. CONCLUSIONS: All variables with a known impact on blood viscosity were altered in the present group of renal transplant recipients. Inappropriate regulation of erythrocyte formation, overweight, the use of CyA, high triglycerides and low HDL-cholesterol levels may be factors contributing to this. The importance of impaired flow properties of blood for the development of cardiovascular diseases and transplant glomerulosclerosis needs to be examined.     

Effects of dietary fish oil on serum lipids and blood coagulation in peritoneal dialysis patients

The effects of a daily fish oil supplement rich in eicosapentaenoic acid were studied in 11 stable continuous ambulatory peritoneal dialysis (CAPD) patients. Serum lipids, platelet aggregation studies, and template bleeding times were determined before and after 4 weeks of fish oil treatment. The lipid studies were repeated approximately 20 weeks after stopping fish oil supplement. At the end of the treatment period, serum triglycerides (mean +/- SEM) decreased from 297 +/- 42 to 211 +/- 29 mg/dL (P less than .01), high density lipoprotein (HDL) cholesterol fell from 45 +/- 3 to 41 +/- 3 mg/dL (P less than .05), and low density lipoprotein (LDL) cholesterol increased from 172 +/- 16 to 208 +/- 19 mg/dL (P less than .05). After discontinuing the fish oil supplement, the triglycerides increased to 278 +/- 39 mg/dL, which was no different than the value before fish oil treatment. No significant changes occurred in template bleeding time (TBT), platelet count, hematocrit, or platelet aggregation response. Clinically important uremic bleeding was not apparent. We conclude that in CAPD patients a fish oil supplement favorably effects hypertriglyceridemia and can be ingested without promoting uremic bleeding. The likely beneficial impact on atherogenesis resulting from the lowering of the triglycerides may, however, be counteracted by concomitant changes in HDL- and LDL-cholesterol.     

Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients.

Increased serum levels of C-reactive protein (CRP) in uremic and dialysis patients are associated with low serum prealbumin and albumin concentrations and increased mortality and greater risk of cardiovascular disease. Proinflammatory cytokines may cause malnutrition by increasing protein catabolism. Many studies have shown that L-carnitine supplementation leads to improvements in several conditions seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia. L-carnitine therapy may either suppress the inflammatory response or act independently on both inflammation and appetite and/or anabolic processes. Moreover, L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance in patients without renal disease and in hemodialysis and peritoneal dialysis patients. In a pilot study, we provided preliminary evidence that treatment with L-carnitine, 20 mg/kg 3 times weekly at the end of each hemodialysis treatment, was associated with a reduction in serum CRP levels and improvement in anabolic status. The improvement or normalization of serum concentrations of serum CRP also was correlated with increased serum concentrations of albumin, transferrin, and blood hemoglobin. The possibility that some or all of these changes may have been caused by improved nutritional intake cannot be ruled out. Further randomized clinical trials will be necessary to confirm the role of L-carnitine as a modulator of inflammatory protein synthesis in hemodialysis patients.     

L-carnitine infusions may suppress serum C-reactive protein and improve nutritional status in maintenance hemodialysis patients.

Scattered reports indicate that L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance either in patients without renal disease or in maintenance hemodialysis (MHD) or chronic peritoneal dialysis patients. We conducted an experimental study in MHD patients to evaluate the effects of L-carnitine treatment on inflammatory and protein-energy nutritional status. MHD patients were assigned to receive intravenous injections of L-carnitine 20 mg/kg (n = 48) or placebo (n = 65) thrice weekly at the end of each hemodialysis treatment for 6 months. The carnitine-treated group showed a statistically significant decrease in serum C-reactive protein and increase in serum albumin and transferrin, blood hemoglobin, and body mass index. Conversely, in the placebo-treated group, a significant decrease was reported for serum albumin, serum transferrin, and body mass index, whereas the other considered measures did not change significantly. These preliminary findings suggest that in MHD patients, L-carnitine therapy may suppress inflammation, particularly among those patients with C-reactive protein > or =3 mg/dL, and may improve protein-energy nutritional status.     

Cytokine release and serum lipoprotein (a) alterations during hemodialysis

It has been reported recently that a number of cytokines, mainly tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, and IL-6, can alter lipid metabolism and produce hyperlipidemia. Studies in hemodialysis (HD) patients have demonstrated increased production of these cytokines during HD. In order to investigate any possible relationship between changes of cytokines and lipid concentrations during HD in the serum of 25 uremic patients on chronic HD using modified cellulose membranes, TNFalpha, IL-1beta, IL-6, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein a (Lp[a]), and total proteins were measured immediately before (pre-HD) and after HD (post-HD), in one session. The post-HD values were corrected according to the hemoconcentration based on the changes in serum total proteins. Serum TNFalpha and IL-1beta levels were significantly increased from 38.24 +/- 17.85 pg/ml and 2. 60 +/- 3.64 pg/ml pre-HD to 48.86 +/- 25.21 and 3.49 +/- 4.08 pg/ml post-HD, p < 0.001 and p < 0.05 respectively. Also Lp(a) levels presented a statistically significant increase post-HD and were almost doubled (pre-HD: 15.41 mg/dl, to post-HD: 27.39 mg/dl, p < 0. 05). Serum IL-6 as well as serum TC, TG, HDL-C, and LDL-C did not show any statistically significant alterations during HD. A significant positive correlation was detected between TNFalpha and Lp(a) values post-HD (r: 0.413, p: 0.04), but not between pre-HD values. No further relationship between serum cytokines and the other estimated lipid parameters was observed, either between pre- or post-HD values. Our results indicate that release of TNFalpha and IL-1beta during HD have no effect on serum lipids concentration, except on Lp(a). It seems that the acute rise of this lipoprotein during hemodialysis may be related with the TNFalpha overproduction.     

Lipid Metabolism in Non-Uremic and Uremic Dogs During and After Hemodialysis with Acetate

Plasma triglyceride and cholesterol concentrations were elevated in dogs after nephrectomy induced uremia. Plasma triglyceride concentrations remained constant during a 4-hour period of hemodialysis of uremic and non-uremic dogs against an acetate concentration of 39. 5 mM (delivering 3 mEq/Kg/hr) plus infusion of 12. 5 µ;Ci/Kg/hr of acetate-1-¹⁴C, but rose progressively following dialysis. Radioactivities in plasma phospholipids, triglycerides and cholesteryl esters increased during dialysis and continued to rise in the post dialysis period, whereas ¹⁴C activity in free fatty acids and free cholesterol increased during dialysis and decreased post-dialysis. Acetate ¹⁴-C incorporation into plasma triglycerides was similar in the uremic and non-uremic groups, but incorporation into plasma cholesterol was higher in the uremics. Liver triglyceride concentrations and radioactivities at 12 hours were higher in the uremic dogs. At this time, adipose tissue ¹⁴C incorporation was also higher in uremic dogs but no differences were observed in aorta, heart or sciatic nerve incorporation. The results suggest that acetate may contribute to the increased plasma triglyceride concentrations observed following dialysis, and that uremia further accentuates acetate incorporation into plasma cholesterol and liver triglycerides.     

Rate of weight loss after vertical banded gastroplasty in morbid obesity: relationship to serum lipids and uric acid

The relationship between postoperative weight loss after vertical banded gastroplasty in morbidly obese patients and preoperative serum triglycerides, cholesterol, HDL-cholesterol, uric acid and fasting plasma glucose was evaluated. The rate of weight loss, calculated as a percentage of original weight, was determined at three and six months after surgery. There was a significant correlation between rate of weight loss at three months and preoperative serum uric acid (r = -0.60, p less than 0.01). and also with the total cholesterol: HDL-cholesterol ratio (r = 0.61, P less than 0.01). At six months, the rate of weight loss correlated with preoperative serum triglycerides (r = -0.54, p less than 0.02) and total cholesterol: HDL cholesterol ratio (r = 0.44, p less than 0.05). The reasons for the predictive value of these biochemical parameters is unknown and deserves further study.     

Platelet aggregation in chronic renal failure--whole blood aggregation and effect of guanidino compounds

Studies were performed on the platelet aggregation (PA) in patients with chronic renal failure (CRF) and normal subjects (NS). The PA was investigated in the whole blood by the electrical impedance method. The concentrations of plasma (P-) and erythrocyte (E-) guanidinosuccinic acid (GSA) and methylguanidine (MG) in uremic patients with CRF were determined by high performance liquid chromatography. GSA and MG are guanidino compounds (GC) and have been widely shown to act as uremic toxins. The effects of GSA and/or MG on the PA of NS were also investigated. The results showed that the PA of conservative therapy patients with CRF was significantly lower than that of NS, while the PA of hemodialysis (HD) patients was improved. The PA of continuous ambulatory peritoneal dialysis (CAPD) patients was rather high and the possibility of sugar and lipid metabolic disorders was suggested as the cause. The concentrations of P- and E-GSA and MG in uremic patients with CRF were increased. But there were no significant correlations between the PA and the concentrations of GSA and MG. In vitro, GSA and/or MG at a high concentration exerted a significant inhibitory effect, while at a low concentration they showed a lesser inhibitory effect on the PA. In conclusion, based on their inhibition of the PA in patients with CRF, the dialyzable materials, GSA and MG, are considered to represent active uremic toxins.     

Multifactorial genesis of enhanced platelet aggregability in patients with nephrotic syndrome

Platelet aggregation, beta-thromboglobulin (beta-TG) and platelet factor 4 (PF 4) release and thromboxane B2 (TxB2) formation in stimulated platelet-rich plasma were investigated in 13 patients with nephrotic syndrome who had normal serum creatinine levels (creatinine clearance greater than 70 ml/min/1.73 m2). In contrast to 13 sex- and age-matched controls, spontaneous platelet aggregation only occurred in patients with nephrotic syndrome with correlation to serum albumin and plasma fibrinogen levels. The EC50 (estimated concentration of aggregating agent to cause half maximum velocity of primary aggregation) for ADP and collagen and threshold concentration of arachidonic acid (threshold AA) were decreased in patients with nephrotic syndrome, reflecting a hyperaggregable state. In patients with nephrotic syndrome EC50 ADP values were significantly correlated to serum albumin, serum cholesterol and plasma fibrinogen, however, EC50 collagen or threshold AA did not correlate to these parameters. Plasma beta-TG levels were increased in patients, whereas plasma PF 4 levels were not significantly changed in patients compared to controls. In vitro TxB2 formation was elevated in patients only after stimulation with AA. Nevertheless, after stimulation with collagen and ADP, TxB2 formation was unchanged in patients compared to controls. Platelet hyperaggregability in nephrotic patients was confirmed in our study. However, unchanged thromboxane B2 formation after collagen stimulus as well as missing correlations between EC50 collagen or threshold AA and serum albumin were contradictory to the hypothesis that enhanced AA availability due to hypoalbuminemia is responsible for platelet hyperaggregability. Platelet hyperaggregability in terms of EC50 ADP being associated with serum albumin levels as well as to serum cholesterol and plasma fibrinogen indicate a multifactorial genesis.     

血液透析前补充左卡尼汀对改善终末期尿毒症患者透析耐受性的影响

目的 探讨不同时段静脉补充左卡尼汀对终末期维持性血液透析患者透析过程中发生低血压、肌肉痉挛及透析患者耐受性的影响和血浆游离肉碱浓度变化.方法 选择终末期维持性血液透析患者30例,按照数字表法随机分为3组:A组为对照组(透析结束后给予左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射)10例,B组(透析前给予左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射,透析结束后左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射)10例,C组(透析开始2h后给予左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射,透析结束后给予左卡尼汀1.0g加入0.9％氯化钠20ml静脉注射)10例.观察各组用药前、用药4周、8周及12周后各项指标的变化、血浆肉碱浓度和血液透析充分性.结果 B、C两组患者较对照组临床症状及分级显著好转,差异有统计学意义(P＜0.05);游离血浆肉碱浓度较对照组升高,差异有统计学意义(P＜0.05);患者透析的耐受力和尿素氮清除效率(Kt/V)明显好转,差异有统计学意义(P＜0.05).结论 在透析前或透析中给予左卡尼汀即刻补充剂量能降低患者发生透析不良反应的风险,增加患者的透析耐受力,提高患者透析的充分性.     

Impact of hemodialysis on endogenous plasma and muscle carnitine levels in patients with end-stage renal disease

BACKGROUND: End-stage renal disease (ESRD) patients undergoing hemodialysis treatment have reduced plasma L-carnitine levels; however, the relationship between dialysis age and carnitine status is poorly understood. This study examined the relationship between duration of dialysis and plasma and skeletal muscle concentrations of L-carnitine and its esters in ESRD patients. METHODS: Blood samples were collected from 21 patients at baseline and throughout the first 12 months of hemodialysis. In 5 patients, muscle samples were obtained after 0, 6, and 12 months of hemodialysis. Blood and muscle samples were collected from an additional 20 patients with a mean dialysis age of 5.10 years. L-carnitine, acetyl-L-carnitine, and total L-carnitine were measured by high-performance liquid chromatography (HPLC). RESULTS: The mean +/- SD plasma L-carnitine concentration in ESRD patients who had not yet started hemodialysis was 50.6 +/- 20.0 micromol/L. Significantly lower concentrations were observed after 12 months (29.7 +/- 10.5 micromol/L) and >12 months (22.0 +/- 5.4 micromol/L) of hemodialysis treatment. Acetyl-L-carnitine also declined with dialysis age, while plasma nonacetylated acylcarnitines continued to increase with the progression of hemodialysis therapy. An inverse relationship between dialysis age and muscle L-carnitine concentrations was observed. CONCLUSION: Long-term hemodialysis treatment is associated with a significant reduction in endogenous plasma and muscle L-carnitine levels and a significant increase in plasma acylcarnitines. The majority of the change in plasma L-carnitine concentrations occurs within the first few months of hemodialysis, while muscle levels continue to decline after 12 months of treatment.