Electrolytes and free amino acids in leg skeletal muscle of young and elderly women

Electrolytes and/or amino acids were determined in leg skeletal muscle biopsies from elderly (age range 57-75 years) and young (age range 20-35 years) apparently healthy women. When compared to the young group, the elderly one was characterized by increased levels of muscular Na+ and Cl-, while the calculated intracellular concentration of Na+ was reduced. The pattern and levels of free amino acids showed only minor differences between elderly and young women. Intracellular Mg2+ and K+ showed a significant correlation with muscle levels of simultaneously determined energy-rich phosphagen compounds that was published previously.     

Amino acid concentration in the interstitium of human skeletal muscle: a microdialysis study

BACKGROUND: The microdialysis technique has been widely used for in vivo monitoring of the interstitial composition of several tissues. Remarkably high concentrations of taurine and glycerol were reported in a recent human study. As taurine and glycerol are predominantly present in the intracellular space, cellular trauma after probe insertion may have resulted in elevated interstitial concentrations. With the present study we wanted to investigate the impact of the initial trauma on the interstitial concentrations of amino acids and glycerol. METHODS: Microdialysis probes were inserted into the vastus lateralis muscle in eight subjects. Using a slow perfusion rate of 0.3 muL min-1, dialysate samples were collected in five 75-min periods. Simultaneously, plasma samples were taken from a peripheral vein for amino acid determination. RESULTS: During the first collection period, the dialysate concentration for 21 measured amino acids was on average 180% +/- 51% higher than the concentration in plasma water. This difference decreased to 52% +/- 15%, 32% +/- 8%, 37% +/- 8% and 31% +/- 7% during periods 2, 3, 4 and 5 respectively. Carnosine, which is not present in plasma, was detected in high concentrations in the interstitium during the first collection period and decreased subsequently. CONCLUSION: In the post-absorptive phase, the concentrations of most amino acids in muscle interstitium are slightly higher than in venous plasma water. The leakage of intracellular amino acids, because of probe insertion, will initially lead to an overestimation of the actual interstitial concentration of amino acids. Therefore, reliable baseline values of amino acids cannot be obtained until 120-150 min after probe insertion. The dialysate concentration of carnosine may be used as a marker of cellular leakage.     

Improvement of cardiac function after haemodialysis. Quantitative evaluation by colour tissue velocity imaging.

BACKGROUND: Overhydration and accumulation of uraemic toxins may influence the myocardial function in haemodialysis (HD) patients. To evaluate cardiac function and the effects of fluid and solute removal during a single session of HD, colour tissue velocity imaging (TVI) was used. This new technique, which is less load dependent than conventional echocardiography, allows an objective quantitative assessment of myocardial contractility, contraction and relaxation. METHODS: Conventional echocardiographic and TVI images were recorded before and after a single HD session in 13 clinically stable HD patients (62+/-10 years, six males) and in 13 sex- and age-matched healthy controls. Myocardial tissue velocities (v; cm/s) for isovolumetric contraction (IVC), peak systole (PS), early (E') and late (A') diastolic filling and strain rate (SR) were measured. RESULTS: Left ventricular hypertrophy (LVH) was present in 12 patients. TVI gave additional information in comparison with conventional echocardiography. Before HD, PS (5.0+/-0.8 vs 6.0+/-1.2 cm/s, P<0.05), E' (5.7+/-1.7 vs 7.3+/-2.0 cm/s, P<0.05) and A' (6.6+/-1.7 vs. 8.3+/-2.9 cm/s, P<0.05) velocities were lower in the patients than in the controls, indicating systolic and diastolic dysfunction. The HD session increased IVCv (4.0+/-1.7 to 5.5+/-1.9 cm/s; P<0.001), PSv (5.0+/-0.8 to 5.7+/-0.8 cm/s; P<0.05) and SR (0.7+/-0.2 to 0.9+/-0.2 1/s; P < 0.05) and decreased E/E' (16.7+/-7.7 to 12.2+/-4.0, P<0.05), indicating improved systolic function and decreased LV filling pressure, respectively. Linear regression analysis demonstrated a dependency of systolic contraction (PSv) and contractility (IVCv) upon plasma levels of phosphate (r(2) = 0.70, P<0.005, r(2) = 0.33, P<0.01). CONCLUSIONS: Using TVI, HD patients demonstrate myocardial dysfunction, which is found less frequently when using conventional echocardiography. The systolic function seems to be impaired by high plasma levels of phosphate and an increased Ca x P product. One single session of HD improved systolic function as indicated by increases in IVCv, PSv and SR. Further studies are needed to clarify if this effect of HD is due to the acute removal of fluid, the removal of solutes or both.     

Impact of inflammation on epigenetic DNA methylation – a novel risk factor for cardiovascular disease?

OBJECTIVE: The lifespan of dialysis patients is as short as in patients with metastatic cancer disease, mainly due to cardiovascular disease (CVD). DNA methylation is an important cellular mechanism modulating gene expression associated with ageing, inflammation and atherosclerotic processes. DESIGN: DNA methylation was analysed in peripheral blood leucocytes from three different groups of chronic kidney disease (CKD) populations (37 CKD stages 3 and 4 patients, 98 CKD stage 5 patients and 20 prevalent haemodialysis patients). Thirty-six healthy subjects served as controls. Clinical characteristics (diabetes mellitus, nutritional status and presence of clinical CVD), inflammation and oxidative stress biomarkers, homocysteine and global DNA methylation in peripheral blood leucocytes (defined as HpaII/MspI ratio by the Luminometric Methylation Assay method) were evaluated. CKD stage 5 patients (n=98) starting dialysis treatment were followed for a period of 36 +/- 2 months. RESULTS: Inflamed patients had lower ratios of HpaII/MspI, indicating global DNA hypermethylation. Analysis by the Cox regression model demonstrated that DNA hypermethylation (HpaII/MspI ratio 相似文献   

Muscle water and electrolytes in patients undergoing continuous ambulatory peritoneal dialysis

Muscle water and electrolytes were determined in percutaneous muscle biopsy material from m. quadriceps femoris in 33 uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) for 1-38 months, and in 34 normal subjects. The patients showed increased muscle contents of water, sodium, and chloride relative to fat-free solids (FFS); both intra- and extracellular water contents were increased. The total water content was inversely correlated with the duration of CAPD. The muscle potassium content was increased, both relative to FFS and to magnesium, whereas the intracellular potassium concentration was normal. Despite hypermagnesemia, the muscle content of magnesium was normal and the intracellular concentration was even slightly decreased due to the increase in intracellular water. We conclude that muscle water and electrolyte status is abnormal in CAPD patients, but the alterations appear to be less marked than in uremic patients undergoing other forms of therapy.     

Effect of hemodialysis on protein synthesis

BACKGROUND: Earlier studies have shown that hemodialysis (HD) treatment stimulates net protein catabolism. Several factors associated with HD affect protein catabolism, such as an inflammatory effect due to blood-membrane contact and loss of amino acids and glucose into the dialysate. SUBJECTS, MATERIAL AND METHODS: We have studied protein synthesis in skeletal muscle of healthy volunteers (n = 9) before and after a single heparin-free HD. Protein synthesis (PS) was studied, using 2 independent techniques: the incorporation of labeled 2H5-phenylalanine into muscle protein, which gives a quantitative measure of the fractional synthesis rate of muscle proteins, and the concentration and size distribution of ribosomes, which gives a qualitative estimate of protein synthesis. Furthermore, free amino acid concentrations were determined in muscle and plasma. RESULTS: The rate of PS, expressed as the fractional synthesis rate, decreased by 13% during HD (p < 0.02). The capacity for PS, as reflected by the total concentration of ribosomes, was reduced by 22% (p < 0.02) and the activity of PS, expressed as the relative proportion of polyribosomes, decreased from 48.4 +/- 0.9% to 44.8 +/- 0.8% after dialysis (p < 0.01). There was a total loss of 5.8 +/- 0.3 g amino acid to the dialysate. Plasma and muscle free amino acid concentrations were determined at four time points; before and after the phenylalanine incorporation period, before dialysis and before and after the second incorporation period after dialysis. Immediately after dialysis, there was a decrease in plasma asparagine, histidine, alanine, taurine, valine and tryptophane. In muscle, no changes occurred except for a slight increase in leucine after dialysis. In blood, the glucose concentration decreased and the total amount of glucose lost to the dialysate was 21 +/- 3.0 g. In summary, one single hemodialysis treatment decreases fractional protein synthesis rate in skeletal muscle. CONCLUSION: The results demonstrate substantial losses of amino acids and glucose to the dialysate and decreased amino acid concentrations in plasma, but only minimal changes in the intracellular amino acid concentrations in muscle, suggesting that the decreased PS is caused not by lack of amino acid precursors at the site of the synthesis activity, but by other mechanisms.     

Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance

In the present study, we explore the role of decreased renal function and a genetic polymorphism on the recently discovered protein resistin, apparently able to inhibit hepatic insulin action in mice. We also investigate possible links with inflammation and the insulin resistance present in patients with chronic kidney disease (CKD). This is a post hoc, cross-sectional study comparing 239 prevalent CKD patients with varying degrees of renal function impairment with an age- and gender-matched randomly selected control group of 25 individuals. Glomerular filtration rate (GFR) was estimated by the mean of urea and creatinine clearance (24-h urine samples) (n=204) or by iohexol clearance (n=60). Plasma analysis of blood lipids, insulin, glucose, inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, vascular cellular adhesion molecule, intercellular adhesion molecule) and resistin (kit from LINCO Research, St Charles, MS) was performed using commercially available assays or routine methods. Insulin resistance was estimated by quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment for insulin resistance (HOMA-IR) and body composition by dual-energy X-ray absorptiometry. Genotyping of a C/G promoter single nucleotide polymorphism (n=168) at position -180 of the resistin gene was performed by PyroSequencing. Serum levels of resistin were markedly elevated in the CKD patients with both advanced (39.9+/-1.3 ng/ml) and mild to moderate (23.2+/-1.0 ng/ml) renal function impairment, as compared to controls (8.5+/-0.7 ng/ml; P<0.001). In a multiple linear regression model in patients (adjusted r(2)=0.60), only GFR (beta=3.4; P<0.0001), lean body mass (beta=2.2; P<0.001) and the inflammatory markers were independently associated with circulating resistin levels. There was a weak but significant impact of -180 C/G genotype on plasma levels of resistin (median 43.0+/-2.4 ng/ml in CC, 37.5+/-2.0 ng/ml in CG, and 41.1+/-4.9 ng/ml in GG; P<0.05). Univariate analysis of non-diabetic patients and controls showed that serum resistin was associated with markers of glucose metabolism. However, in a multiple regression model, resistin, as well as all the measured markers of inflammation, was only associated with insulin resistance if GFR was not taken into account. Circulating resistin levels are strongly associated with both GFR and inflammatory biomarkers in CKD. As the significant relationship between plasma resistin levels and insulin resistance was lost following the correction for GFR, resistin is not a likely mediator of insulin resistance in patients with CKD. Renal function is an important factor to take into account in clinical studies relating insulin sensitivity to inflammatory biomarkers in CKD as well as in patients with diabetes mellitus, who often have an impaired renal function.     

Glucose intolerance in uremic patients: the relative contributions of impaired beta-cell function and insulin resistance

Glucose tolerance and tissue sensitivity to insulin were examined in 19 renal failure patients on chronic regular hemodialysis (group U) and in 6 matched control subjects with normal renal function (group A). Based on glucose tolerance as assessed by an oral glucose tolerance test (OGTT), glucose tolerance was normal in 5 (group U:N), borderline in 5 (group U:BL) and decreased in 9 uremic subjects (group U:D). Compared with group A the uremics demonstrated significantly (p less than 0.01) impaired insulin sensitivity as assessed by a continuous mixed infusion of somatostatin, insulin and glucose (SIGIT). In addition 19 non-diabetic subjects with normal fasting blood glucose and normal renal function, matching the uremic patients with respect to glucose tolerance as assessed by OGTT, were studied (group B). In group B impairments in both insulin secretion and insulin sensitivity tended to be more pronounced in subjects with decreased OGTT as compared with those with borderline OGTT. In contrast, insulin resistance was present to a similar degree in uremic subjects of group U:N, U:BL and U:D. During SIGIT endogenous insulin, glucagon and growth hormone (GH) were suppressed in both uremic and control subjects. This implies that insulin resistance in uremia is most likely not due to hyperglucagonemia or abnormal GH metabolism. During OGTT subjects of group U:N had significantly higher insulin response than subjects of group U:BL (p less than 0.02) and group U:D (p less than 0.01). Insulinogenic index was significantly higher in group U:N than in group U:BL (p less than 0.02) and group U:D (p = 0.01) and was higher in group U:BL than in group U:D (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of in vivo contact between blood and dialysis membranes on protein catabolism in humans

To investigate whether the contact between blood and dialysis membranes might induce muscle protein degradation, the exchange of free amino acids across leg tissues was measured by catheterization technique in three groups of healthy subjects before and after a 150 minute sham-hemodialysis procedure (SHDP), that is, in vivo passage of blood (100 ml/min) through a dialyzer but with no circulating dialysate. Dialyzers with either regenerated cellulose membrane (group CU, N = 10 and group CU-IND, N = 6) or polyacrylonitrile membrane (group AN, N = 8) were used in group CU-IND indomethacin was administered before (100 mg) and at the end (50 mg) of SHDP. Leg blood flow was measured by venous occlusion plethysmography. In group CU net leg release of tyrosine and phenylalanine increased from 3.4 +/- 0.8 and 3.6 +/- 0.8 nmol/min/100 g tissue, respectively, before SHDP to 7.8 +/- 1.8 and 8.3 +/- 1.8 nmol/min/100 g tissue, respectively, at 345 minutes after the start of SHDP (P less than 0.01). The total release of all measured amino acids increased from 148 +/- 31 to 309 +/- 50 nmol/min/100 g tissue (P less than 0.01). The results indicate that interaction between blood and regenerated cellulose membranes leads to accelerated net protein breakdown. In group CU-IND no change in leg amino acid release was observed following SHDP, suggesting that the increased net protein catabolism is mediated by prostaglandins. Sham hemodialysis using AN membranes did not result in increased amino acid efflux from leg tissues, implying that the protein catabolic effect of blood-membrane contact depends on the biochemical properties of dialyser.     

What is the role of controls in an outpatient department on progression of renal disease?

Evidence that protein restriction retards the progression of chronic renal failure in man is mostly derived from anecdotic data and retrospective studies with inappropriate controls and inferior methodology for evaluating renal function. Data from a prospective randomized study in Stockholm demonstrate that more frequent clinical follow-ups without changing the dietary intake of protein significantly retards the progression of renal failure and that the degree of retardation is correlated to improvement in blood pressure control.