Effect of L-carnitine on the kinetics of carnitine, acylcarnitines and butyrobetaine in long-term haemodialysis.

BACKGROUND: The current study was performed to investigate the kinetics of carnitine, individual acylcarnitines and butyrobetaine in patients on haemodialysis. METHODS: Eight stable long-term haemodialysis patients were studied under basal conditions (no carnitine supplementation) and 3 weeks after intravenous supplementation with l-carnitine (10 or 20 mg/kg body weight) after each haemodialysis session. The kinetic studies included serial determinations of carnitine and metabolites just before, during or between haemodialysis sessions. Analysis was performed by liquid chromatography-tandem mass spectrometry. RESULTS: Before haemodialysis, the plasma concentrations were (micromol/l) 15.1+/-0.6 (mean+/-SEM) for carnitine, 5.9+/-0.7 for acetylcarnitine, 0.66+/-0.04 for propionylcarnitine and 0.98+/-0.08 for butyrobetaine (basal conditions) or 142+/-23 for carnitine, 69+/-12 for acetylcarnitine, 6.0+/-1.1 for propionylcarnitine and 2.6+/-0.3 for butyrobetaine (carnitine 20 mg/kg). During haemodialysis, the plasma concentrations dropped by approximately 80% for all compounds determined, with extraction coefficients ranging from 0.65 to 0.86. In patients supplemented with 20 mg/kg carnitine, the amount of carnitine removed by haemodialysis equalled 42% of the dose administered, consisting of 2.08 mmol carnitine, 1.03 mmol acetylcarnitine and 0.051 mmol propionylcarnitine. Between the haemodialysis sessions, carnitine, acylcarnitines and butyrobetaine reached apparent steady-state concentrations within 1 day both under basal conditions and after supplementation. CONCLUSIONS: Patients on haemodialysis have reduced carnitine, acylcarnitine and butyrobetaine plasma levels, which can be increased by supplementing carnitine. Propionylcarnitine, an important constituent of the acylcarnitine pool, can be removed by haemodialysis. Removal of potentially toxic acyl-groups may represent a mechanism for a beneficial effect of carnitine in these patients.     

Amino acid and carnitine supplementation in haemodialysed children

Plasma carnitine, amino acids and lipids levels were studied in ten uraemic children treated with haemodialysis and given amino acid supplementation with and without carnitine. As carnitine is synthesised from lysine and methionine and has a significant influence on lipid metabolism, the relationship between these was examined. Amino acid supplementation (0.25 g/kg body weight) was started with the intention of improving the plasma amino acid pattern in these children and increasing the concentration of lysine, which is the substrate for carnitine synthesis. Amino acids were administered i. v. during dialysis and carnitine (25 mg/kg body weight i. v.) was administered after dialysis three times a week. Concentrations of most essential amino acids were decreased in these patients. The first period of amino acid supplementation did not increase plasma levels of the essential amino acids, with the exception of tyrosine (P<0.01). After the second period of supplementation, methionine was increased (P<0.01), isoleucine was decreased (P<0.01), but tyrosine normalised and was significantly lower than after the first period (P<0.05). Thus overall amino acid supplementation did not improve amino acid levels; it was inconsistently associated with a further decrease in highdensity lipoprotein-cholesterol and an increase in total protein levels. Lysine concentrations after amino acid supplementation remained low. Paradoxically, before carnitine supplementation a positive correlation between free carnitine and triglycerides was observed. The plasma carnitine concentration, initially very low, was excessively high after carnitine supplementation. After carnitine administration no amelioration of any of the other biochemical indices was observed. Carnitine supplementation was associated with a significant reduction of total protein levels (P<0.01). In children with end-stage renal disease on haemodialysis, neither amino acid nor carnitine supplementation appear to result in significant improvements in plasma levels of essential amino acids or lipids.     

Nutritional-inflammation status and resistance to erythropoietin therapy in haemodialysis patients.

BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.     

Influence of sex and chronic haemodialysis treatment on total, free and acyl carnitine concentrations in human serum

The influence of sex and haemodialysis treatment on serum total, free and acyl carnitine concentrations in healthy controls and chronic renal failure patients has been investigated. Patients on regular haemodialysis treatment generally displayed significantly decreased serum carnitine levels. The mean predialysis serum carnitine levels were not significantly different from the mean healthy control values. However, after dialysis a significant decrease in serum carnitine levels was observed compared to the predialysis and healthy control values. Moreover, serum ratio of acylated to free carnitine was significantly higher after haemodialysis, as compared to both healthy controls and predialysis patients. Sex-related changes in serum total, free and acyl carnitine levels and ratios of acylated to free carnitine have been observed in healthy controls and patients on chronic haemodialysis treatment.     

Intradialytic serum protein concentrations differ between nightly nocturnal and conventional haemodialysis

AIM: Nocturnal haemodialysis (NHD) is a new haemodialysis (HD) modality that has been shown to have many benefits when compared with conventional haemodialysis (CHD). Previous results from our NHD programme have demonstrated a 7% fall in the postdialysis serum albumin concentration when compared with the pre-HD levels. A similar, physiological, 9% haemodilution of albumin is seen in normal individuals on assuming a supine posture. METHOD: In this observational study, the intradialytic change in the concentration of 11 serum proteins (total protein, albumin, alkaline phosphatase, gamma glutamyl transferase, alanine transaminase, amylase, transferrin, complement factors 3 and 4, free thyroxine and C-reactive protein (CRP)) was measured in 10 patients on NHD and in 10 age- and sex-matched controls on CHD. The ultrafiltration rate (UFR) was also recorded. RESULTS: We demonstrated an intradialytic fall in the total protein (0.63%), albumin (2.40%), alkaline phosphatase (1.84%), amylase (8.82%), complement factor 3 (2.73%) and CRP (8.19%) in patients on NHD. This was of a lesser magnitude than that occurring in the pilot study but still approximated the physiological fall in serum proteins occurring with overnight recumbency in normal individuals. In contrast, all serum proteins measured rose during CHD, reflecting intravascular volume contraction and haemoconcentration. The UFR was significantly lower in NHD than CHD (234.52+/-20.90 mL/h vs 435.38+/-38.44 mL/h, P<0.001). CONCLUSION: We concluded that NHD is a modality that facilitates the use of a low UFR and hence the slow removal of volume which, in turn, results in a minimal perturbation of the normal recumbent volume distribution mechanism and the partial preservation of the normal physiological response to recumbency of the serum protein concentration.     

Nutritional effects of carnitine supplementation in hemodialysis patients

AIMS: Carnitine is involved in fatty acid metabolism and it is cleared by dialysis. As it plays a role in energy utilization and because malnutrition is a frequent complication of HD treatment, we studied the effects of carnitine supplementation on several nutritional parameters in HD patients. MATERIAL AND METHODS: The main selection criterion was a body mass index (BMI; body weight/(height)2) < 22 kg/m2. Fifty-three patients were enrolled to participate in this open and randomized study. For 6 months, 28 patients received 15 mg/kg of intravenous L-carnitine at the end of each hemodialysis (HD) treatment (Group A), the remaining 25 patients were controls (Group B). The measured parameters were the post-dialysis body weight, serum albumin concentration (nephelemetry), food intake assessed by a 3-day food questionnaire, nPNA (normalized protein equivalent of nitrogen appearance), creatinine generation, and anthropometry. RESULTS: Forty-five patients completed the study (Group A: 14 F/9 M, 66.7 years old; Group B: 11 F/11 M, 65.2 years old). At the beginning of the study, there were no differences between the groups for age, gender, HD duration, BMI, diabetes prevalence, plasma carnitine levels and measured nutritional parameters. 65.2% and 77.3% in each group were carnitine-deficient (plasma total carnitine level < 35 micromol/l). After 6 months of L-carnitine supplementation, none of the nutritional parameters had changed in either group, except that serum albumin concentration decreased in both groups. Dividing each group according to their respective median serum albumin concentrations, daily energy and protein intakes, creatinine generation or triceps skinfold thickness did not show any difference in the various nutritional parameters with or without carnitine supplementation. CONCLUSION: Carnitine supplementation, despite normalization of plasma carnitine levels, has no effect on the nutritional status of HD patients.     

Effect of fish protein supplementation on aminoacid profile and nutritional status in haemodialysis patients.

Plasma concentrations of aminoacids, albumin, prealbumin, transferrin, C3 and C4 complement, and anthropometric measurements were determined before and after oral administration of a new preparation of fish protein in 19 haemodialysis patients participating in a randomised, double-blind, placebo-controlled crossover study lasting 6 months. Furthermore, plasma concentrations of aminoacids were measured in 24 control subjects. Before fish protein dietary supplementation, serine, threonine, tyrosine, valine, methionine, isoleucine, phenylalanine, leucine, and lysine were lower than in control subjects. Serine, histidine, valine, tyrosine, methionine, isoleucine, leucine, and lysine increased after treatment, and phenylalanine tended to increase. The ratios of essential: non-essential aminoacids and alanine:branched-chain aminoacids (BCAA) became normal, whereas valine: lycine and serine:glycine increased significantly and tyrosine:phenylalanine was unchanged. Plasma protein concentrations were unchanged after treatment. Serum transferrin, triceps and subscapular skinfolds, and bodyweight index were slightly reduced in the patients, whereas arm muscle circumference was normal. Bodyweight, weight index, and arm muscle circumference increased after active treatment. In conclusion, the increase in body weight and the return to normal of the plasma aminoacid profile and aminoacid ratios seem to indicate that the treatment with this new fish protein preparation may have beneficial effects on some of the nutrition-related abnormalities in haemodialysis patients.     

Carnitine and Weakness in Haemodialysis Patients

Weakness in haemodialysis patients has been attributed to severalfactors including carnitine deficiency. Malnutrition, neuropathy,uraemic myopathy and parathyroid hormone excess may all be important. Six haemodialysis patients were shown to have reduced musclepower compared with a normal population, and to be malnourishedby dietary assessment, and features of their weakness were investigated. Total carnitine was normal in plasma but elevated in muscle,with an excess of esterified carnitine in both plasma and muscleand diminished free plasma carnitine. Muscle biopsy showed nofeatures of carnitine deficiency and electromyography showeda non-specific neuropathy with additional myopathic changesin some. Dietary supplementation with L-carnitine (2 g/day)for 6 weeks in a placebo-controlled trial showed a redistributionof carnitine fractions but no subjective or objective improvementin muscle function. There was no improvement in the plasma lipidprofile. The weakness of haemodialysis patients is multifactorial. Wehave not demonstrated total carnitine depletion in either muscleor plasma, and oral supplementation of L-carnitine has no demonstrableeffect in this group.     

维持性血透患者血清NGAL水平与体内铁存储的相关性研究

目的:探讨在维持性血液透析患者,其血清NGAL(中性粒细胞明胶酶相关载脂蛋白)水平与体内铁存储的关系。方法:从2010年10月开始,我们纳入我院血液透析患者人数150例,同时纳入50例健康人为对照。收集患者及健康对照人群的人口学资料、相关的临床和生化学资料,透析前后NGAL及透析前CRP、转铁蛋白饱和度、铁蛋白、血清铁、转铁蛋白等。做透析前血清NGAL与CRP、转铁蛋白饱和度、铁蛋白、血清铁、转铁蛋白相关性分析。评估NGAL水平在判断体内铁存储的价值。结果:(1)血液透析患者其血清NGAL透析前水平为(445.45±50.34)ng/ml,透析后为(369±50.34)ng/ml,差异有统计学意义(P<0.05)。(2)血液透析患者其血清NGAL水平与CRP、spKt/V、TSAT等指标均有正相关关系(P<0.05),但与铁蛋白、血清铁、转铁蛋白无明显线性关系(P>0.05)。在多元线性回归模型中,NGAL水平与CRP、spKt/V、TSAT有相关关系(P<0.05)。(3)ROC曲线表明,NGAL水平较铁蛋白更好的反映体内铁存储情况,但差异无统计学意义(P>0.05)。结论:在血液透析患者,血清NGAL与spKt/V、CRP、TSAT有不同程度的正相关。血清NGAL能较好的反映体内铁存储情况。     

Positive correlation of CRP and fibrinogen levels as cardiovascular risk factors in early stage of continuous ambulatory peritoneal dialysis patients

We aimed to study the relationship between the C-reactive protein (CRP), albumin, and fibrinogen as cardiovascular risk factors in continuous ambulatory peritoneal dialysis (CAPD) patients, in the early stage of their therapy. The study included 21 CAPD patients as the study group (SG) and age- and sex-matched 21 healthy patients as the control group (CG). History and physical exam data were obtained for all cases, and demographic baseline characteristics were taken. Twelve-hour fasting serum levels of glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride, total protein, albumin, hemoglobin, CRP, and fibrinogen were obtained. There was no statistically significant difference between the SG and CG in baseline characteristics, including age, sex, body mass index (BMI), smoking, and family history of cardiovascular disease. However, diabetes mellitus (DM) and hypertension (HTN) were significantly more common among the study group. The average total protein, albumin, and hemoglobin levels were significantly lower, and the CRP and fibrinogen levels were significantly higher (p < 0.001) in the SG. A positive correlation was seen (r = 0.443, p < 0.05) among CRP and fibrinogen levels in SG. There was no correlation among the other parameters in SG. For CG, there was no correlation seen for any studied parameters. When patients with and without cardiovascular disease (CVD) were compared, no correlation was seen between CRP and other parameters. A positive correlation of CRP and fibrinogen levels as cardiovascular risk factors was shown in early stage of CAPD patients. The CAPD patients with elevated levels of CRP and fibrinogen should receive close follow-up for cardiovascular disease prevention.     

Carnitine and carnitine esters in acute renal failure

Plasma concentrations of carnitine and carnitine esters were determined in patients with multiple forms of acute renal failure with and without sepsis, and also before and after haemodialysis therapy. Total carnitine, free carnitine, short-chain and long-chain acylcarnitine values of both groups of acute renal failure patients were markedly elevated compared with healthy subjects and chronically uraemic patients undergoing regular haemodialysis treatment. Carnitine and carnitine esters did not differ between septic and non-septic patients before and after haemodialysis with dialysers made of cuprophane or polysulphone. Animal experiments with acutely uraemic rats were performed in order to determine whether the liver or the kidney may be responsible for elevated carnitine and carnitine esters in acute renal failure. Plasma and liver total carnitine, free carnitine, short-chain acylcarnitine and long-chain acylcarnitine were significantly elevated in sham-operated animals, and further in ureter ligated and bilateral nephrectomised rats. Skeletal muscle and heart muscle carnitine and carnitine esters remained the same as in sham-operated controls. Our data demonstrate markedly increased liver carnitine synthesis and carnitine acylation in an acute uraemic rat model even after binephrectomy and 48-h food depletion and in the presence of elevated serum carnitine concentrations. Furthermore, from our clinical study we conclude that there is no need for carnitine supplementation in patients who developed acute renal failure in the postoperative and post-traumatic state under adequate nutrition even when requiring daily haemodialysis.     

Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis.

BACKGROUND: Anorexia may be associated with decreased plasma levels of branched-chain amino acids (BCAA). In malnourished elderly haemodialysis (HD) patients, oral BCAA supplementation may improve anorexia, resulting in improved nutritional status. METHODS: Among 44 elderly (age >70 years) patients on chronic HD, 28 patients with low plasma albumin concentration (<3.5 g/dl) were classified as the malnourished group; they also suffered from anorexia. The other 16 patients did not complain of anorexia and were classified as the well-nourished group. We performed a 12-month, placebo-controlled, double-blind study on the malnourished group. Fourteen patients each received daily oral BCAA supplementation (12 g/day) or a placebo in random order in a crossover trial for 6 months. Body fat percentage, lean body mass, plasma albumin concentration, dietary protein and caloric intakes, and plasma amino acid profiles were monitored. RESULTS: Lower plasma levels of BCAA and lower protein and caloric intakes were found in the malnourished group as compared to the well-nourished group. In BCAA-treated malnourished patients, anorexia and poor oral protein and caloric intakes improved within a month concomitant with the improvement in plasma BCAA levels over the values in well-nourished patients. After 6 months of BCAA supplementation, anthropometric indices showed a statistically significant increase and mean plasma albumin concentration increased from 3.31 g/dl to 3.93 g/dl. After exchanging BCAA for a placebo, spontaneous oral food intake decreased, but the favourable nutritional status persisted for the next 6 months. In 14 patients initially treated with a placebo, no significant changes in nutritional parameters were observed during the first 6 months. However, positive results were obtained by BCAA supplementation during the subsequent 6 months, and mean plasma albumin concentration increased from 3.27 g/dl to 3.81 g/dl. CONCLUSIONS: Normalization of low plasma levels of BCAA by oral supplementation can reduce anorexia and significantly improve overall nutritional status in elderly malnourished HD patients.     

Inflammation and pruritus in haemodialysis patients.

BACKGROUND: Pruritus is a common symptom among patients on haemodialysis (HD). We studied 68 HD patients to assess the role of iron deficiency, anaemia, inflammation and other common serum and dialysis parameters in pruritus. METHODS: The patients were questioned about the occurrence of pruritus at home, quantified according to frequency ('never', 'occasionally' and 'every day') and intensity ('absent', 'moderate' and 'severe'). The blood and serum variables considered were: haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, hypochromic red blood cells (RBC), hyperchromic RBC, microcytic RBC, macrocytic RBC, reticulocytes, iron, ferritin, transferrin, transferrin saturation, C-reactive protein (CRP), urea, creatinine, calcium, phosphorus, albumin, total protein and glucose. We also analysed Kt/V, age and time on HD treatment. Patients were divided into 3 groups according to the frequency or intensity of their pruritus, and we analysed and compared the variables between the 3 groups. RESULTS: Half (50%) of the patients reported never having pruritus, 32.4% occasionally and 17.6% every day. Pruritus was moderate in 41.2% of them and severe in 8.8%. None of the parameters considered revealed any statistically relevant differences between the three pruritus frequency groups, except for mean serum transferrin level (mg/dl) ('never'=268+/-64 vs 'occasionally'=244+/-40 vs 'every day'=217+/-56, P<0.05). As for the intensity of the symptom, mean serum transferrin (268+/-64 vs 247+/-39 vs 174+/-31, P<0.001) and median ferritin levels (mg/dl) (83 (11-420) vs 98 (11-1121) vs 293 (111-471), P<0.05) showed statistically significant differences between the 3 groups, as did albumin levels (g/dl) (4.3+/-0.4 vs 4.2+/-0.4 vs 3.7+/-0.4, P<0.05). Median CRP values (mg/dl) tended to be higher in patients with more frequent (0.4 (0.3-5.5) vs 0.7 (0.3-11.4) vs 0.9 (0.3-13.5)) and more severe pruritus (0.4 (0.3-5.5) vs 0.7 (0.3-4.0) vs 2.1 (0.3-13.5)), but those differences were not statistically significant. CONCLUSIONS: Iron deficiency and anaemia seem to play no part in HD-related pruritus, whereas lower serum transferrin and albumin levels and higher ferritin values are consistent with the possible role of inflammation in the development and severity of pruritus.     

Iron absorption in erythropoietin-treated haemodialysis patients; effects of iron availability, inflammation and aluminium

Background: The response to recombinant human erythropoietin (rHuEpo) is determined primarily by the availability of iron. In contrast to i.v. iron, oral iron supplementation is often insufficient for an optimal response. Method: We studied iron absorption and the effects of iron status, aluminium status and inflammation in 19 chronic haemodialysis patients on maintenance rHuEpo therapy. Iron mucosal uptake after 24 h, iron retention after 2 weeks and mucosal transfer of iron were determined with a whole-body counter using an oral dose ⁵⁹Fe. Iron absorption was measured once without, and once after the ingestion of 2 g aluminium hydroxide. Results: On the basis of transferring saturation, two groups of dialysis patients were distinguished: a group with a functional iron deficiency (n=9), and an iron-deficient dialysis patients group, mucosal uptake, mucosal transfer, and iron retention were 49.9%±29.4, 0.73±0.29, and 41.6%±32.2, being significantly lower than in a non-uraemic iron deficient population (P <0.01, P <0.05, P <0.01 respectively). In the iron-replete dialysis patients group, mucosal uptake, mucosal transfer, and iron retention were 20.0±12.3, 0.59±0.18, and 11.1±6.7, mucosal uptake and iron retention being lower than in a normal iron-replete population (P <0.0005 and P <0.003 respectively). Dialysis patients with high C-reactive protein (CRP) values showed lower iron absorption. Iron absorption data correlated significantly with transferrin saturation and CRP in the iron-deficient group, and with serum ferritin in the iron-replete group. Iron absorption decreased after an aluminium hydroxide challenge in the iron-deficient patients to the lower levels of the iron-replete subjects. Body aluminium stores, estimated by the desferrioxamine test, did not correlate with parameters of iron absorption. Conclusion: The absorption of iron in dialysis patients is decreased in haemodialysis patients, which may, at least in part, be due to inflammation. Aluminium ingestion further reduces absorption in functional iron-deficient patients. Key words: anaemia; erythropoietin; iron absorption; haemodialysis      

Carnitine supplementation vs. medium-chain triglycerides in postburn nutritional support

The effect of dietary supplementation of carnitine on protein metabolism was studied in a burned guinea-pig model. Animals bearing a 30 per cent total body surface area burn were enterally infused with three isocaloric and isonitrogenous diets via gastrostomy feeding tubes for 14 days. Two diets contained safflower oil (long-chain triglycerides, LCT) and another diet contained medium-chain triglycerides (MCT) as their lipid sources (30 per cent of total calories as lipid). L-Carnitine was added to one of the two diets containing safflower oil. There were no significant differences in nitrogen balance, urinary excretion, serum albumin or transferrin among the three groups. However, the use of MCT in place of LCT appeared to increase liver weight and liver nitrogen. In this model, carnitine supplementation did not enhance the nitrogensparing effect of fat following burn injury.     

Carnitine supplementation improves apolipoprotein B levels in pediatric peritoneal dialysis patients

There have been conflicting reports concerning the effect of carnitine supplementation on lipid metabolism in patients on peritoneal dialysis (PD). We investigated several parameters of lipid metabolism in pediatric PD patients supplemented with carnitine. The study included 20 patients receiving PD (treatment group) aged 2–18 years and a matched healthy control group. In the treatment group, baseline triglyceride, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and apolipoprotein B levels were higher than in the control group. High-density lipoprotein cholesterol, free fatty acid, phospholipids, and apolipoprotein A-I levels were not different from those in the control group. The baseline plasma free carnitine level was lower and acyl-carnitine level was higher in the treatment group. No difference was found between the groups with respect to plasma total carnitine levels. Oral l-carnitine supplementation (50 mg/kg per day for 30 days) led to a significant decrease (from a baseline value of 146.6±51.8 mg/dl to 63.6±22.2 mg/dl, P<0.001) in apolipoprotein B levels, and no significant change in the other lipid parameters of the treatment group. Oral l-carnitine supplementation does not ameliorate the lipid profile in pediatric PD patients, but it causes a significant decrease in apolipoprotein B levels. Hence, carnitine supplementation may be recommended for decreasing apolipoprotein B levels in this patient population.     

Inflammation and reduced albumin synthesis associated with stable decline in serum albumin in hemodialysis patients

BACKGROUND: The concentration of albumin in serum is maintained by its rates of synthesis, catabolism, and distribution between vascular and extravascular compartments. Albumin synthesis is suppressed when there is inflammation or inadequate protein intake. This study was conducted to establish whether a decline in serum albumin of >0.3 g/dL was accompanied by a change in albumin synthesis and if so whether these changes were associated with increased levels of acute phase proteins and/or with a decrease in equilibrated normalized protein catabolic rate (enPCR). METHODS: Seventy-nine patients in the National Institutes of Health (NIH)-sponsored HEMO Study had baseline measurements of albumin synthesis (measured kinetically as the disappearance of [125]I human serum albumin), the serum concentrations of albumin, transferrin, C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1AG), ceruloplasmin, interleukin-6 (IL-6), plus monthly measurements of enPCR. The plasma levels of all proteins and enPCR were measured regularly over 2 years or until serum albumin decreased by >0.3 g/dL on two sequential measurements. Albumin synthesis was measured a second time when serum albumin declined by >0.3 g/dL or after 2 years. RESULTS: Fifty-nine patients [21 with a significant decrease in serum albumin (decliners) and 38 with stable values of serum albumin] had albumin synthesis measured twice. A decline in albumin concentration and synthesis was associated with an increase in alpha1AG when data from all patients were analyzed as a group. In decliners, albumin synthesis decreased significantly but was unchanged in stable. Likewise, in decliners, IL-6, CRP, alpha1AG, and ceruloplasmin increased significantly but were unchanged in stable. enPCR was unchanged in both groups and was not associated with either changes in albumin level or synthesis in the whole group. CONCLUSION: A decrease in serum albumin of >0.3 g/dL that persists for a period of 6 weeks is associated a decrease in albumin synthesis. This response is associated with evidence of activation of the acute phase response (inflammation) but not with changes in enPCR. In well-dialyzed patients, inflammation is the principal cause of a decrease in serum albumin while protein intake plays an insignificant role.     

腹腔镜直肠癌Miles手术对机体应激反应和内脏蛋白的影响

目的:探讨腹腔镜直肠癌Miles手术对机体应激反应和内脏蛋白的影响。方法:将60例行直肠癌Miles手术的患者按其意愿分为腹腔镜组和开腹组,每组30例,于术前、术后第1、2、3天晨检测血C反应蛋白(CRP),IL-6及内脏蛋白,包括白蛋白(ALB)、前白蛋白(PRE)、转铁蛋白(TRF)、视黄醇结合蛋白(RBP)的变化。结果:两组CRP、IL-6术后1~3d较术前均明显升高(P<0.01),腹腔镜组术后CRP、IL-6明显低于开腹组(P<0.01)。两组术后ALB、PRE、TRF、RBP较术前明显下降(P<0.01)。术后第2天腹腔镜组PRE高于开腹组(P<0.01),术后第3天腹腔镜组ALB、PRE、TRF、RBP均明显高于开腹组(P<0.01)。结论:腹腔镜直肠癌Miles手术较开腹手术机体创伤及应激反应小,有利于机体内脏蛋白的恢复。     

Procalcitonin: a new marker of inflammation in haemodialysis patients?

BACKGROUND: Although procalcitonin (PCT) has been described as a new marker of infection and inflammation, it has not been extensively studied in dialysis patients. METHODS: We measured plasma PCT levels in 62 patients on maintenance haemodialysis (30 M/32 F, age 61.8+/-17.1 years, on dialysis for 75+/-93 months, 12 h/week, with a Kt/V of 1.53+/-0.31, high-flux membrane being used in 25 patients and low-flux in 37 patients, without reuse). PCT levels were compared with other markers of inflammation and nutritional status, including C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), leukocytes, urea, creatinine, albumin, prealbumin, normalized protein catabolic rate (nPCR), haemoglobin (Hb), and epoetin (Epo) doses. Patients were divided into different groups according to their infectious and vascular status. RESULTS: PCT plasma levels before dialysis were 0.69+/-0.81 ng/ml. Fifty-seven per cent of PCT values were higher than the upper normal limit of 0.5 ng/ml. CRP and PCT concentrations were high in patients with a current infection, while IL-6 values were elevated in all patients regardless of infection status. Plasma CRP concentrations before dialysis were 21.2+/-31.4 mg/l, and 70% of these values were higher than the upper normal limit. CRP, PCT, IL-6, and fibrinogen were positively correlated with each other and were all negatively correlated with albumin. Prealbumin was negatively correlated with CRP and IL-6. In the 43 patients treated with Epo, haemoglobin was negatively correlated with IL-6 and Epo doses, while Epo doses were positively correlated with IL-6 but not with CRP or PCT. The 23 patients with both elevated PCT and CRP plasma levels had the lowest Hb, albumin, and prealbumin concentrations, and the highest fibrinogen concentrations and Epo doses. CONCLUSION: PCT in haemodialysis patients is positively correlated with currently used markers of inflammation such as CRP and fibrinogen, and negatively correlated with markers of nutritional status such as albumin. The concomitant elevations in PCT and CRP could be more sensitive in the evaluation of inflammation than each marker separately.     

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.