Serum free carnitine, carnitine esters and lipids in patients on peritoneal dialysis and hemodialysis

Serum free and esterified carnitine levels as well as lipids were investigated in patients undergoing regular hemodialysis (HD) treatment before and during 12 weeks of treatment with L-carnitine (1 g i.v.) at the end of each HD. The results were compared with those obtained in patients on continuous ambulatory peritoneal dialysis (CAPD; n = 15) or intermittent peritoneal dialysis (IPD; n = 3) and healthy controls (CO; n = 20). In HD patients (n = 23) total carnitine (TC) was 49.9 +/- 3.9 (CO: 46.0 +/- 2.5; NS), free carnitine (FC) was 31.6 +/- 2.8 (CO: 37.4 +/- 1.3; p less than 0.05), short-chain acylcarnitine (SCC) was 17.0 +/- 1.8 (CO: 7.2 +/- 0.9; p less than 0.0001) and long-chain acylcarnitine (LCC) was 1.2 +/- 0.2 mumol/l (CO: 0.6 +/- 0.1; p less than 0.05). FC was in the normal range in CAPD (35.6 +/- 3.2) and IPD (44.5 +/- 8.0 mumol/l) patients, whereas SCC (30.1 +/- 3.5) and LCC (2.9 +/- 0.2) levels were maximal elevated in IPD patients (11.8 +/- 0.8 and 1.5 +/- 0.2 on CAPD). Therefore, TC was higher in IPD than in CAPD patients (77.5 +/- 5.0 vs. 49.0 +/- 3.5 mumol/l). 12 weeks after L-carnitine supplementation in HD patients, TC was 313.9 +/- 22.6, FC was 207.7 +/- 12.4, SCC was 99.6 +/- 12.1 and LCC was 7.1 +/- 0.6 mumol/l. TC and FC were significantly lower in females compared with males. Total cholesterol and ketone bodies were normal, HDL cholesterol was significantly decreased before and after L-carnitine supplementation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma concentration and peritoneal clearance of oxalate in patients on continuous ambulatory peritoneal dialysis (CAPD)

Accumulation of oxalate, resulting in high plasma levels, is a common finding in end-stage renal disease. We investigated plasma concentration and peritoneal clearance of oxalate in 14 patients on continuous ambulatory peritoneal dialysis. The plasma oxalate levels in these patients (30.2 +/- 11.2 mumol/l) were as high as those in hemodialysis patients before dialysis (31.9 +/- 11.1 mumol/l). There was a significant correlation between plasma oxalate and urea nitrogen appearance (UNA). Dietary protein seems to be an important oxalate source in these patients, because the UNA reflects protein intake in stable patients. The mean peritoneal oxalate clearance was 6.64 +/- 1.56 l/day, close to the creatinine clearance. These results suggest that the plasma oxalate levels in CAPD patients may be sufficiently high to induce calcium oxalate deposition, and that methods of increasing oxalate removal and reducing oxalate burden are necessary for CAPD patients.     

Carnitine status of pediatric patients on continuous ambulatory peritoneal dialysis

Plasma carnitine and the effect of oral carnitine supplementation on serum triglycerides was studied in 12 pediatric patients receiving continuous ambulatory peritoneal dialysis (CAPD). Baseline evaluation of all patients included plasma carnitine and serum triglyceride values. Following randomization into two groups, only group 2 patients received oral L-carnitine supplementation, 100 mg/kg/day, for 2 months. The initial laboratory evaluation was repeated at the conclusion of the study. Plasma carnitine values were also determined from a control population. Mean baseline plasma carnitine concentrations of group 1 (39.8 +/- 8.0 nmol/ml) and group 2 (45.2 +/- 10.3 nmol/ml) patients were not significantly different from each other or from the control population. Serum triglyceride values were elevated in both groups (group 1 - 206.5 +/- 100.0 mg/dl; group 2 - 279.3 +/- 74.5 mg/dl). After 2 months, the mean plasma carnitine concentration of group 2 patients increased to 147.7 +/- 84.1 nmol/ml, significantly greater than the value of group 1, 32.8 +/- 8.0 nmol/ml (p less than 0.004). However, no significant change in the serum triglyceride level was noted in either group. We conclude that the plasma carnitine status of pediatric patients receiving CAPD is normal and that oral carnitine supplementation does not lead to the resolution of hypertriglyceridemia.     

Taurine levels in plasma and blood cells in patients undergoing routine maintenance hemodialysis

We compared taurine levels in plasma, erythrocytes, platelets, lymphocytes, and granulocytes from 11 normal adults and 11 maintenance hemodialysis (MHD) patients immediately before and following a routine hemodialysis treatment. Taurine concentrations were elevated in plasma predialysis, as compared with normal subjects (90 +/- 16 [SEM] v 54 +/- 2 mumol/L [1.1 +/- 0.2 v 0.7 +/- 0.03, mg/dL]), but decreased with a dialysis treatment (to 34 +/- 3 mumol/L [0.4 +/- 0.04 mg/dL]). Erythrocyte taurine levels tended to be higher in MHD patients predialysis (1.2 +/- 0.2 v 0.7 +/- 0.1 nmol/10(9) cells, P less than 0.05 where P less than 0.025 is significant) as compared with controls; erythrocyte taurine was increased after dialysis (to 1.8 +/- 0.3 nmol/10(9) cells, P less than 0.006). In contrast, platelet taurine concentrations in MHD patients were lower than normal predialysis (18 +/- 2 v 27 +/- 2 nmol/10(9) cells) and declined further during the dialysis procedure (to 14 +/- 1). Granulocyte and lymphocyte taurine levels were not different in MHD patients, as compared with normal adults, either before or after dialysis. The observed differences in blood cell taurine content (expressed per 10(9) cells) could not be explained by variation in cell volumes among the groups examined. Thus, both chronic renal failure and a routine hemodialysis treatment produce changes in cell and plasma taurine levels that tend to be specific for the individual cell type.     

High fluoride exposure in hemodialysis patients

The observation of higher plasma flouride levels in our hemodialysis (HD) patients than our continuous ambulatory peritoneal dialysis (CAPD) patients (4.0 +/- 0.5 mumol/L [n = 17] v 2.5 +/- 0.3 mumol/L [n = 17], P less than 0.005) prompted an evaluation of fluoride metabolism during HD. We found that serum fluoride was completely ultrafiltrable across cuprophane membranes (99% +/- 4%) and that HD produced acute changes in plasma fluoride levels that correlated well with the fluoride gradient between plasma and dialysis fluid at the start of dialysis. Our HD fluids contained significantly higher fluoride concentrations than were present in commercially prepared peritoneal dialysis fluid. Our fluids are prepared from fluoridated tap water that is purified by reverse osmosis (RO). We conclude that the different concentrations of fluoride in our dialysis fluids account for the differences in the plasma flouride concentrations between our dialysis groups. Since many HD units rely on RO systems to purify fluoridated tap water, it is likely that many HD patients are being exposed inadvertently to increased concentrations of fluoride.     

Oral l-carnitine does not decrease erythropoietin requirement in pediatric dialysis

The use of recombinant human erythropoietin (rhEPO) has greatly facilitated the treatment of anemia in children with chronic renal failure, but is expensive. Several reports on adult patients have shown that supplementation with l-carnitine can decrease the requirement for rhEPO. The objective of this study was to investigate the effect of oral supplementation with l-carnitine on the rhEPO requirement in children on dialysis. We investigated 16 children on dialysis (11 hemodialysis, 5 peritoneal dialysis) with a median age of 10.2 years. All children were stable on rhEPO treatment at least 3 months before study entrance. After obtaining baseline data, all children were supplemented with l-carnitine 20 mg/kg/day. Data were collected for 26 weeks. Follow-up was completed for 12 patients (8 hemodialysis, 4 peritoneal dialysis). At baseline free carnitine (32±18 μmol/l) and total carnitine levels (54±37 μmol/l) were normal. At the end of the study free carnitine levels had increased to 97±56 μmol/l (P<0.05) and total carnitine levels to 163±90 μmol/l (P<0.05). There was no significant change in rhEPO requirement. Hemoglobin level or hematocrit did not change significantly during the study. In conclusion we could not demonstrate a beneficial effect of supplementation with l-carnitine on rhEPO requirement in children on dialysis. Received: 17 September 1999 / Revised: 14 April 2000 / Accepted: 17 April 2000     

Serum myoglobin in patients on intermittent and continuous ambulatory peritoneal dialysis

Serum myoglobin levels were determined in patients maintained on chronic peritoneal dialysis. Eleven intermittent peritoneal dialysis patients had a mean serum myoglobin of 174 +/- 29 ng/ml. In 7 patients tested serially, there was no consistent change in serum myoglobin: the mean level was 154 +/- 36 ng/ml pre-dialysis and 170 +/- 20 ng/ml post-dialysis. Seventeen patients on continuous ambulatory peritoneal dialysis had a mean serum myoglobin of 215 +/- 18 ng/ml. Two patients given oral carnitine supplements had a substantial decrease in their serum myoglobin levels. Patients on peritoneal dialysis, like those on hemodialysis, tend to have elevated serum myoglobin levels, and neither form of dialysis affects serum myoglobin concentration. This hypermyoglobinemia may be due to metabolic changes in muscle.     

Vitamin B6 requirements of patients on chronic peritoneal dialysis

Patients with chronic renal failure often develop vitamin B6 deficiency, which is of clinical concern because the multiorgan system manifestations are similar to those of uremia. Vitamin B6 deficiency in hemodialysis patients has been previously studied, but the need for daily pyridoxine supplementation in patients on chronic peritoneal dialysis (CPD) remains unclear. Therefore, we studied a group of 11 stable patients, nine on CAPD and two CCPD, to test for vitamin B6 deficiency and to establish daily requirements. Adequacy of vitamin B6 nutrition was assessed by measurement of plasma and dialysate effluent total vitamin B6 and pyridoxal 5'-phosphate (PLP), the latter using a very sensitive modification of the tyrosine apodecarboxylase enzyme assay. After four weeks without vitamin B6 supplements on a diet containing 1.3 +/- 0.2 mg vitamin B6/day (7.7 +/- 1.2 mumol/day), all patients had subnormal plasma PLP levels, 16 +/- 3 nmol/liter (nml 40 to 60), seven having a severe deficiency (less than or equal to 20 nmol/liter). Plasma total vitamin B6 levels (which includes non-PLP forms of the vitamin) were normal in all patients at baseline, 116 +/- 29 nmol/liter. Peritoneal losses were small, 8 +/- 2 nmol PLP/day and 545 +/- 61 nmol total vitamin B6/day. Supplementation with 5 mg/day oral pyrodoxine HCl for up to 16 weeks adequately repleted eight patients (65 +/- 7 nmol PLP/L), while three patients required 10 mg/day to achieve normal plasma PLP levels. During three episodes of peritonitis, dialysate losses of PLP did not increase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum erythropoietin levels and hematocrit in end-stage renal disease: influence of the mode of dialysis

Serum erythropoietin (Ep) levels were measured by radioimmunoassay in 70 patients with end-stage renal disease (ESRD) to evaluate the influence of the mode of dialysis on the relationship between serum Ep levels and the severity of anemia. Thirty-five patients were on hemodialysis (HD), seven were on intermittent peritoneal dialysis (IPD), and 28 were on continuous ambulatory peritoneal dialysis (CAPD). Compared to HD, CAPD patients had higher serum Ep (CAPD), 46.1 +/- 13.4 v HD, 16.9 +/- 2.2 mU/mL) and hematocrit (CAPD, 33.9 +/- 2.5 v HD, 24.8 +/- 1.4%; P less than 0.05). The Ep and Hct values for IPD patients were intermediate between the other two groups. Serum Ep levels were higher in CAPD patients in the first 4 weeks of initiation of CAPD (144 +/- 35 mU/mL, n = 6) than later (39 +/- 6.4 mU/mL, n = 24). A significant fluctuation in serum Ep and Hct values was noted in patients on all three modes of dialysis, when multiple samples were obtained at different time intervals. There was a weak correlation between serum Ep and Hct in the three groups of dialysis patients; r = 0.36, P less than 0.005. The data suggest that CAPD provides a better biochemical milieu for Ep production and responsiveness than HD treatment of ESRD.     

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.     

Whole blood serotonin levels are markedly elevated in patients on dialytic therapy.

The normal range for whole blood serotonin levels in chronic renal failure patients has not been defined. As serotonin may be implicated in platelet abnormalities, hypo- and hypertension and itch in dialysis patients, serotonin whole blood levels were measured in a group of patients with chronic renal failure and/or who were dialysis dependent. The levels were elevated in 12 patients with moderate (mean serum creatinine 335 +/- 54 mumol/l) chronic renal failure (270 +/- 46 micrograms/l) compared to 11 normals (163 +/- 17 micrograms/l, p less than 0.05; quoted normal range less than 300 micrograms/l) but did not correlate with serum creatinine levels. There was a marked elevation in serotonin levels in dialyzed patients, including those on hemodialysis (polysulfone, n = 6, 747 +/- 234 micrograms/l; cuprophane membranes, n = 6, 708 +/- 198 micrograms/l), hemodiafiltration (n = 12, 695 +/- 130 micrograms/l) and especially peritoneal dialysis (n = 6, 1,148 +/- 162 micrograms/l). All results were significant (p less than 0.01) compared to normals and compared to the nondialyzed group (p less than 0.05). The level of serotonin decreased during hemodialysis regardless of the membrane used. There was no positive correlation of serotonin levels with pruritus or hypertension, although there was a negative correlation with systolic blood pressure. The reference range for serotonin whole blood levels needs to be broadened when considering dialyzed patients.     

Plasma levels of human atrial natriuretic factor in patients treated by hemodialysis and continuous ambulatory peritoneal dialysis

We measured plasma levels of immunoreactive human atrial natriuretic factor (ANF) in chronic renal failure patients treated by hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). Predialysis plasma ANF was significantly higher in HD patients (271.8 +/- 173.4 pg/ml) as compared to CAPD patients (81.8 +/- 80.5 pg/ml) and healthy subjects (31.5 +/- 19.8 pg/ml). Plasma volume was higher in HD patients than in CAPD patients. Plasma ANF and plasma volume showed a significant positive correlation. In HD patients, high plasma ANF value decreased significantly to a value comparable with that of CAPD patients after each dialysis. The removal rates of ANF by HD and CAPD were comparable. Ultrafiltration corresponding to 2% of body weight without dialysis also reduced plasma ANF. Thus, the difference in plasma ANF values between HD and CAPD patients seems to be mostly due to the difference in plasma volume, indicating that plasma ANF is sensitive to volume status even in chronic dialysis patients.     

The nutritional/metabolic and hormonal effects of 8 weeks of continuous ambulatory peritoneal dialysis with a 1% amino acid solution

Circulating intermediary metabolites, hormones and plasma amino acids (AA) were measured at intervals over 24 hours in seven non-diabetic patients with chronic renal failure treated by continuous ambulatory peritoneal dialysis (CAPD), before and after an 8-week period during which a 1% amino acid dialysis solution replaced two of the four dextrose exchanges. Mean 24-hour concentrations of plasma total and essential amino acid were higher following the AA dialysate (total pre: 2893 +/- 185; total post: 3357 +/- 244; p less than 0.05; essential pre: 751 +/- 47; essential post: 1064 +/- 57 mumol/l; p less than 0.001). Mean 24-hour concentrations of the branched chain amino acids leucine, isoleucine and valine were higher following the AA dialysate (valine pre: 201 +/- 18; valine post: 321 +/- 19; p less than 0.001; leucine pre: 102 +/- 6; leucine post: 127 +/- 9; p less than 0.01; isoleucine pre: 67 +/- 5; isoleucine post: 85 +/- 7 mumol/l; p less than 0.05). Serum albumin increased with use of the AA dialysate (pre: 36 +/- 1; 2 weeks, 40 +/- 1; 4 weeks, 40 +/- 1; 6 weeks, 41 +/- 1; 8 weeks, 38 +/- 2 g/l). 24-hour profiles and mean 24-hour concentrations of blood glucose, serum insulin, serum triglyceride, plasma non-esterified fatty acids (NEFA), plasma 3-hydroxybutyrate and plasma alanine were unchanged after the AA period. Plasma bicarbonate decreased with use of the amino acid solution (pre: 21 +/- 1; 2 weeks, 18 +/- 1; 4 weeks, 18 +/- 1; 6 weeks, 16 +/- 1; 8 weeks, 16 +/- 1 mmol/l). Use of a 1% amino acid solution over an 8-week period in CAPD patients improves the plasma amino acid profile but results in a metabolic acidosis. The other endocrine and metabolic abnormalities of uremia remain unchanged.     

A study of xanthopterin in chronic renal failure.

Xanthopterin, a metabolic end product of the nonconjugated pterins dihydrobiopterin and tetrahydrobiopterin, is present in many organs and is known to inhibit the proliferation and growth of conconavalin-stimulated lymphocytes. We have developed a simple fluorometric method to measure xanthopterin in the blood and have validated the method by high pressure liquid chromatography (HPLC). Serum levels were 14 +/- 7 nmol/l in normal subjects and 141 +/- 51 nmol/l in hemodialysis patients (p < 0.02). Intermediate levels from patients with renal insufficiency not on dialysis correlated with serum creatinine levels (p < 0.001). Xanthopterin (MW 179) was cleared by hemodialysis at a slightly lower rate than creatinine. It is bound to protein, but the binding, 90 +/- 5% in normal subjects, is decreased in uremia to 60 +/- 15%, p < 0.01. Red cell levels of xanthopterin were five times higher than those of plasma in normal subjects (69 +/- 15 vs. 14 +/- 7 nmol/l, p < 0.001), but uremic patients had lower levels in red cells than in plasma (101 +/- 24 vs. 141 +/- 51 nmol/l, p < 0.05). Slight or moderate hemolysis induced by mechanical stress increased plasma xanthopterin levels by 35%, the effect being more pronounced when hemolysis was severe. We conclude that xanthopterin is increased and its binding to protein is decreased in chronic renal failure. The altered ratio of red cell/plasma xanthopterin levels may reflect an abnormality of the red cell membrane in uremia. We are conducting further studies to amplify our preliminary findings that xanthopterin inhibits cellular growth in vitro.     

Plasma interleukin-6 levels in continuous ambulatory peritoneal dialysis and hemodialysis patients.

Plasma levels of interleukin-6 (IL-6), a cytokine known to be involved in lymphocyte activation and in inflammation, were studied in 10 normal volunteers, 21 continuous ambulatory peritoneal dialysis (CAPD) patients and 41 hemodialysis patients. Plasma IL-6 levels in hemodialysis patients were significantly higher than those in normal volunteers and CAPD patients (p less than 0.05). The means of plasma IL-6 concentrations before and after hemodialysis did not change significantly. While IL-6 in peritoneal dialysate was detectable in only 3 of the 21 CAPD patients without peritonitis, it was extremely high in 2 patients with bacterial peritonitis. IL-6 levels decreased as peritonitis subsided.     

Study on the assay of uremic protein-binding inhibitors: furan compound and hippuric acid]

Plasma levels of 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (FA) and hippuric acid (HA) were studied in healthy subjects, uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD). Analysis of FA and HA in the plasma were performed by gas chromatography with capillary column. The mean value of FA in HD patients (16.7 +/- 6.1 micrograms/ml) was significantly higher than these in healthy subjects (3.6 +/- 1.0 micrograms/ml) and in patients on CAPD (4.1 +/- 3.7 micrograms/ml) (p less than 0.01). HA levels in CAPD and HD groups were higher than those in healthy controls (2.4 +/- 0.8 micrograms/ml). In addition, the values in HD patients (46.7 +/- 53.5 micrograms/ml) were more increased than those in CAPD (18.5 +/- 16.5 micrograms/ml) (p less than 0.05). Approximately 95% of total FA and 25% of HA were bound to the plasma protein. However, the plasma level of HA was significantly reduced by HD therapy, whereas that of FA was not altered. In the previous study, it was described that no effect of HD on the percent of the binding of acid drugs to the plasma protein in the uremic plasma was observed. Therefore it is supposed that FA is more involved in the binding of drugs to the plasma protein in comparison with HA. The peritoneal losses of FA and HA in CAPD were 2.3 +/- 1.3 mg/day and 276 +/- 40 mg/day, respectively. As the duration of HD became longer, plasma concentrations of FA in HD patients were more increased. In general, they were maintained to be comparatively low in patients on CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antioxidant status of elderly chronic renal patients treated by continuous ambulatory peritoneal dialysis

BACKGROUND: An oxidative stress has been reported in patients with chronic renal failure (CRF) treated by haemodialysis. To our knowledge, only scant information is available concerning CRF patients treated by continuous ambulatory peritoneal dialysis (CAPD) with regard to their redox and nutritional status. METHODS: The oxidative stress and the biological nutritional status were evaluated in 20 elderly CRF patients treated by CAPD, compared with a control group of 30 elderly non-CRF patients. Plasma peroxidation products were assayed as thiobarbituric acid-reactive substances (TBARS), and two enzymatic antioxidant systems were determined: erythrocyte superoxide dismutase (SOD), glutathione peroxidase activity in plasma (P-GSH-Px) and in erythrocytes (E-GSH- Px). Selenium, vitamin E, beta-carotene and vitamin A were evaluated as plasma non-enzymatic antioxidants. Nutritional status and iron status were assessed by determining serum albumin, prealbumin, iron, ferritin and transferrin concentrations. RESULTS: Plasma TBARS concentration was high in both groups (CAPD: 1.37 +/- 0.06 mumol/l versus non-CRF: 1.41 +/- 0.06 mumol/l; P = NS), compared with usual values (0.60 to 1.20 mumol/l), on account of the patients' ages. SOD and E-GSH-Px activities were normal in both groups. A significant lowering in P-GSH-Px activity was observed only in CAPD patients (211 +/- 14 U/l, usual values: 480 to 650 U/l). Plasma selenium concentration, decreased in both groups, was significantly lower in CAPD than in non-CRF patients (P < 0.01). Plasma vitamin E, beta-carotene and vitamin A concentrations were significantly enhanced only in CAPD patients (P < 0.0001, P < 0.005 and P < 0.0001, respectively. Biological nutritional markers were similar in both groups and within usual values. CONCLUSIONS: This study demonstrated the existence of an oxidative stress in CAPD-treated elderly CRF patients, evidenced by a decrease in plasma selenium levels and in P-GSH-Px activity. However, plasma TBARS were not higher in CAPD patients than in age-matched non-CRF control subjects, probably on account on the patients' ages.      

Hyperhomocysteinemia in chronic renal failure patients: relation to tissue factor and platelet aggregation

BACKGROUND: A moderate increase in plasma total homocysteine (t-hcy) is considered to be an independent risk factor for cardiovascular disease (CVD) in general population. One of the mechanisms by which hyperhomocysteinemia contributes to cardiovascular risk has been explained to be the increased thrombotic potential. Elevated t-hcy levels were also reported in chronic renal failure patients because the renal function is a major determinant of serum t-hcy levels. PATIENTS AND METHODS: We measured serum hcy and ADP-induced platelet aggregation and plasma tissue factor as a major activator of the coagulation cascade in hemodialysis (HD), peritoneal dialysis (PD) and early stage chronic renal failure (early stage CRF) patients who are not receiving dialysis and compared with those of control. In addition, we also determined serum vitamin B12 and folat levels which are the important factors regulating the metabolism of t-hcy. RESULTS: Hcy levels in all patient groups were significantly higher (HD: 20.42 +/- 1.91 micromol/l, PD: 35.47 +/- 6.30, early stage CRF: 24.39 +/- 3.06) than the normal levels (10.74 +/- 0.74) in spite of standard multivitamin supplementation. The highest t-hcy values were found in peritoneal dialysis patients. Vitamin B12 levels in hemodialysis/peritoneal dialysis patients and folat levels in hemodialysis/early stage CRF patients were also significantly above those of control. On the other hand, the significant elevations in plasma tissue factor concentration were found in all patient groups (HD: 331.4 +/- 31.3 pg/ml, PD: 306.0 +/- 30.0, early stage CRF: 277.2 +/- 25.5 and Control: 69.5 +/- 13.5). t-hcy levels were positively correlated with creatinine (r: 0.791 p < 0.002) and tissue factor levels (r: 0.526 p < 0.05) in only early stage CRF group. The association between t-hcy and tissue factor persisted after these two parameters were adjusted for creatinine (r: 0.649 p < 0.05). On the other hand the same correlations were not observed in dialysis patient groups. In spite of the high tissue factor levels, ADP-induced platelet aggregations were found to be lower in all patient groups (HD: 102.6 +/- 6.7, PD: 98.6 +/- 7.6 and Early stage CRF: 84.9 +/- 7.6) than controls (154.9 +/- 13.7). CONCLUSION: These results suggest that hyperhomocysteinemia and increased tissue factor level are present in patients with renal failure, despite supplementation with vitamin B6 and B12 and folat. However, elevated levels of these thrombogenic factors are not linked with platelet aggregation.     

Elevated plasma glycocalicin levels and decreased ristocetin-induced platelet agglutination in hemodialysis patients

A bleeding diathesis caused by platelet dysfunction is a major cause of morbidity and mortality in patients with uremia. Platelet adhesion to vascular subendothelium is defective in uremia and depends on the interactions of the platelet glycoprotein (GP) Ib/IX complex with the vascular wall. We measured levels of platelet surface GPIb, platelet surface GPIX, plasma glycocalicin (a product of enzymatic cleavage of GPIb), and ristocetin-induced platelet agglutination (RIPA) in patients undergoing chronic hemodialysis compared with patients undergoing peritoneal dialysis and healthy controls. Patients undergoing chronic maintenance hemodialysis have higher levels of platelet surface expression of GPIb (187+/-10 fluorescent units; P < 0.001) than either healthy controls (120+/-4 fluorescent units; P < 0.001) or patients undergoing peritoneal dialysis (127+/-5 fluorescent units; P < 0.001). Similar changes were observed in platelet surface GPIX. Plasma glycocalicin levels were elevated in chronic hemodialysis patients (71+/-5 nmol/L) compared with healthy controls (36+/-3 nmol/L; P < 0.001). Plasma glycocalicin levels also increased progressively throughout the hemodialysis procedure. The slope of RIPA was significantly lower in chronic hemodialysis patients (46+/-3) than in either healthy controls (67+/-4; P < 0.05) or peritoneal dialysis patients (62+/-2; P < 0.05). In conclusion, patients undergoing chronic maintenance hemodialysis have increased plasma glycocalicin levels and decreased RIPA, which may contribute to diminished platelet adhesion to vascular subendothelium and increased bleeding associated with uremia.     

Secondary hyperoxalemia caused by vitamin C supplementation in regular hemodialysis patients

Oxalosis can be a problem in renal failure. As vitamin C is a precursor of oxalate in patients on regular hemodialysis, we have measured plasma levels of vitamin C, oxalate, pyridoxine, thiamine and creatinine twice before and 4 weeks after a change of vitamin C dosage in 49 dialysis patients who had been receiving 500 mg of oral vitamin C daily for more than 6 months. Ten unsupplemented dialysis patients served as controls. The mean plasma levels of vitamin C and oxalate were 3.3 +/- 0.3 mg/dl and 50.4 +/- 8.2 mumol/l respectively. Four weeks after the vitamin C dosage was changed from 500 to 100, 50 and 0 mg, plasma oxalate levels were 34.1 +/- 1.4, 33.3 +/- 3.7, and 25.7 +/- 3.9 mumol/l respectively. There was a strong correlation between plasma vitamin C and oxalate levels (r = 0.755, p less than 0.01) but none between pyridoxine and oxalate. A significant correlation was also noted between the duration of hemodialysis and plasma oxalate levels (r = 0.582, p less than 0.01). Our results suggest that hyperoxalemia in regular hemodialysis patients is aggravated by routine vitamin C supplementation. The administration of vitamin C should be restricted to a dose necessary to correct vitamin C deficiency.