Hyperhomocysteinemia and oxidative stress during dialysis treatment

BACKGROUND/AIMS: The concomitant presence of hyperhomocysteinemia and oxidative stress may represent a determinant factor for the occurrence of vascular alterations and cardiac diseases, the main cause of death among dialysis patients. The aim was to analyze the occurrence of hyperhomocysteinemia and oxidative stress and their possible relationship in dialysis patients. METHODS: Antioxidant substances, homocysteine, folate, and vitamin B12 were determined in blood from 32 patients on hemodialysis (HD), 21 patients on peritoneal dialysis (PD), and 12 healthy individuals. RESULTS: Different degrees of hyperhomocysteinemia were observed in all HD patients and in 95% of the PD patients (45.30 +/- 24.89 microM in HD and 35.50 +/- 26.53 microM in PD). Oxidative stress defined as an imbalance between oxidant and antioxidant forces was observed in all dialysis patients, but was more intense in HD individuals. In this group, lipoperoxidation and protein oxidation were associated with lower concentrations of antioxidants such as erythrocyte vitamin E and vitamin C. CONCLUSIONS: Hyperhomocysteinemia and oxidative stress occur in both types of dialysis treatment, possibly contributing to the establishment of complications in these patients.     

DNA oxidative damage in patients with dialysis treatment

BACKGROUND/AIMS: Chronic renal patients on hemodialysis (HD) and peritoneal dialysis (PD) treatment are exposed to oxidative stress and DNA damage. The objective of this study was to assess the oxidative damage to DNA in end-stage chronic renal failure, before and after vitamin E supplementation. METHODS: Patients on HD (n=29) and PD (n=22) received oral supplementation with 300 mg vitamin E three times a week for 4 weeks. A blood sample was collected at the beginning and at the end of the supplementation cycle for the determination of vitamin E levels (high-performance liquid chromatography), carbonyl groups, and DNA damage (8-hydroxy 2'-deoxyguanosine [8-OHdG] and comet assay). RESULTS: After supplementation, vitamin E concentration was increased by about 50%. Protein oxidation was initially observed in both groups, with a reduction after supplementation. DNA damage detected by the comet assay and by 8-OHdG analysis was significantly reduced (p<0.05) after supplementation in both groups. CONCLUSIONS: Vitamin E supplementation reduced oxidative DNA damage in both HD and PD patients. Treatments such as HD and PD induce oxidative stress and consequent DNA damage, and increased plasma vitamin E levels significantly contribute to the normalization of these events.     

Influence of oral vitamin E therapy on micro-inflammation and cardiovascular disease markers in chronic hemodialysis patients

BACKGROUND: The aim of this study was to evaluate the influence of oral vitamin E therapy on serum concentrations of several markers of micro-inflammation and cardiovascular disease in chronic hemodialysis (HD) patients. METHODS: 29 HD patients were randomized into two groups: 15 patients were treated orally with 400 mg of vitamin E daily for a period of five weeks, and 14 patients received no antioxidant supplementation. Before and after vitamin E therapy, serum concentrations of vitamin E (high-performance liquid chromatography), pregnancy-associated plasma protein-A (immunochemical--TRACE assay), C-reactive protein (nephelometry), intercellular adhesion molecule-1 (ELISA), and E-selectin (ELISA) were measured. HD patients were compared with 16 healthy controls. RESULTS: Baseline serum concentrations of PAPP-A and CRP were significantly higher in HD patients than in healthy controls (PAPP-A: 26.23+/-11.94 vs. 11.41+/-1.94 mIU/L, p<0.001; CRP: 5.20+/-3.50 vs. 3.40+/-3.80 mg/L, p<0.05). After five weeks of oral vitamin E intake, serum PAPP-A, CRP, ICAM-1, and E-selectin concentrations remained unchanged in both groups of HD patients. CONCLUSION: Chronic micro-inflammation in HD patients is documented by the elevation of CRP and PAPP-A. A daily oral dose of 400 mg of vitamin E does not seem to be able to reduce enhanced oxidative stress and micro-inflammation in chronic HD patients.     

Erythropoietin requirements: a comparative multicenter study between peritoneal dialysis and hemodialysis

BACKGROUND: The management of anemia with erythropoietin (EPO) is important in the global treatment of dialysis patients. There is a general impression that anemia control with EPO is obtained more easily in peritoneal dialysis (PD) patients than in hemodialysis (HD) patients. The EPO administration route has to be the same to compare the two techniques adequately. METHODS: To compare EPO action by subcutaneous (SC) route in HD and PD, 132 stable patients were recruited (HD: 69, PD: 63) from six centers, with adequate dialysis criteria (Kt/V in HD >1.3; weekly Kt/V in PD >1.8). In a cross-sectional study, the EPO dose/week, the number of EPO doses/week, hemoglobin (Hb), ferritin, transferrin saturation index (TS), albumin and intact parathyroid hormone (iPTH) were analyzed. Iron treatment, comorbidity and ACE inhibitors (ACEI) and angiotensin II antagonist (AIIA) treatment were recorded. A multivariate regression model was used in the statistical analysis. RESULTS: The mean Hb level was the same in both groups, HD 11.6 (1.3) g/dL, PD 11.4 (1.4) g/dL, p=0.3. The SC, EPO doses required to obtain the Hb levels were higher in HD than in PD patients, with a difference of 64.3 u/Kg/week, statistically significant in the multivariate regression model (p=0.001, 95% CI 42.6-86.0). The number of EPO doses/week was also higher in HD patients (65% of HD patients with > or = 3 doses, 19% of PD patients with three or more doses, p<0.001). TS was similar in both groups, while ferritin was higher in HD patients, with a higher percentage of HD patients using intravenous (i.v.) iron (HD 77% vs. PD 49%, p=0.001). Serum albumin and iPTH were lower in PD patients (p<0.001 and p=0.04, respectively), but the percentage of patients with intact parathyroid hormone (iPTH) >500 pg/mL was similar in both groups (HD 17%, PD 14%). CONCLUSIONS: With the same administration route, PD patients showed a reduced EPO requirement, and less frequent EPO administration than HD patients, to obtain the same Hb level. No other factors, except those involved in better depuration of erythropoiesis inhibitors in PD, seemed responsible for the different EPO requirements.     

DNA Oxidative Damage in Patients with Dialysis Treatment

Background/Aims. Chronic renal patients on hemodialysis (HD) and peritoneal dialysis (PD) treatment are exposed to oxidative stress and DNA damage. The objective of this study was to assess the oxidative damage to DNA in end-stage chronic renal failure, before and after vitamin E supplementation. Methods. Patients on HD (n = 29) and PD (n = 22) received oral supplementation with 300 mg vitamin E three times a week for 4 weeks. A blood sample was collected at the beginning and at the end of the supplementation cycle for the determination of vitamin E levels (high-performance liquid chromatography), carbonyl groups, and DNA damage (8-hydroxy 2′-deoxyguanosine [8-OHdG] and comet assay). Results. After supplementation, vitamin E concentration was increased by about 50%. Protein oxidation was initially observed in both groups, with a reduction after supplementation. DNA damage detected by the comet assay and by 8-OHdG analysis was significantly reduced (p< 0.05) after supplementation in both groups. Conclusions. Vitamin E supplementation reduced oxidative DNA damage in both HD and PD patients. Treatments such as HD and PD induce oxidative stress and consequent DNA damage, and increased plasma vitamin E levels significantly contribute to the normalization of these events.     

Effects of altered volume loading on left ventricular hemodynamics and diastolic filling during hemodialysis

BACKGROUND: Changes in the circulating volume associated with hemodialysis (HD) resulted in alternations of left ventricular (LV) filling. However, previous studies offered conflicting findings. This study thus evaluated the impact of HD on LV diastolic filling indices and hemodynamics. MATERIALS AND METHODS: Forty patients with end-stage renal disease were studied by Doppler echocardiography immediately before and after HD. The cardiac size, volume and mass were determined by M-mode and two-dimensional echocardiography. LV diastolic filling parameters and hemodynamics were assessed from mitral inflow using Doppler echocardiography. RESULTS: Left atrial and LV dimension, LV volume, and LV mass decreased significantly after HD (p<0.001). Cardiac output declined from 5.74+/-1.37 to 4.98+/-1.27 L/min (p<0.001), whereas, the ejection fraction remained unchanged. HD elicited marked changes in the early diastolic E (95.1+/-20.5 to 70.3+/-18.2 cm/s, p<0.001) and late atrial filling A velocities (104.3+/-20.9 to 88.9+/-16.9 cm/s, p<0.001). In addition, correction of the deceleration time of E and isovolumic relaxation time prolonged significantly (p=0.011 and p<0.001, respectively). CONCLUSIONS: Findings in this study indicate that HD altering the loading condition significantly influenced the LV diastolic function and hemodynamics. Moreover, Doppler echocardiography provides an effective means of assessing the effects on LV diastolic filling and hemodynamics during HD.     

Vitamin E-coated dialyzers reduce oxidative stress related proteins and markers in hemodialysis--a molecular biological approach

BACKGROUND: Hemodialysis patients (HD) are exposed to oxidative stress which contributes to cardiovascular disease and accelerated atherosclerosis, major causes of mortality in these patients. A new dialysis membrane coated with vitamin E has been proposed against oxidative stress and atherosclerosis due to their ability to inhibit lipid peroxidation by interacting with scavengers. The mechanisms however are not completely clarified. This study evaluated, using a molecular biology approach, the effect of 6 months treatment with vitamin E-modified dialyzers, CL-E, on the gene expression of oxidative stress related proteins and markers. PATIENTS AND METHODS: To this end, the gene expression of p22phox, a NAD(P)H oxidase subunit closely linked with the generation of superoxide anions and of Heme oxygenase-1 (HO-1), induced by and protective from oxidative stress, were evaluated by RT-PCR in mononuclear cells from 5 patients under 3 times a week chronic bicarbonate dialysis. Hydroperoxide (HPO) and total antioxidant power (AOP) plasma levels were evaluated at 3 and 6 months of treatment. HPO was also evaluated in 8 patients under CL-E treatment for 1 year and compared with 8 patients treated with cuprammonium-ryon filter (TAF). RESULTS: p22phox mRNA decreased from 0.61 +/- 0.05 d.u. to 0.48 +/- 0.03, p < 0.01 while HO-1 increased from 0.55 +/- 0.04 d.u. to 0.62 +/- 0.03, p < 0.01. HPO decreased in CL-E treated patients: from 2.72 +/- 0.26 microM to 1.45 +/- 0.27 at 3 months (p < 0.001) to 0.87 +/- 0.11, p < 0.001 at 6 months, while AOP increased: from 752 +/- 90 mmol/L to 1057 +/- 105, p < 0.001 at 6 months. HPO was also reduced in 1 year Excebrane CL-E treated patients compared with cuprammonium treated patients: 2.25 +/- 0.3 vs. 1.42 +/- 0.11 microM, p < 0.001. CONCLUSION: The reduced expression of oxidative stress related proteins and markers gives further support to the efficacy of the use of Vitamin E coated dialysers for the prevention or slowing progression of cardiovascular disease and atherosclerosis, major complications and causes of mortality in these patients in which oxidative stress plays a pivotal role.     

Influence of parenteral iron therapy and oral vitamin E supplementation on neutrophil respiratory burst in chronic hemodialysis patients

BACKGROUND: Bioincompatibility of hemodialysis (HD) membranes is responsible for neutrophil activation leading to oxidative stress, which can be further increased by intravenous (IV) iron (Fe) administration. The aim of our study was to monitor neutrophil respiratory burst during HD and to find out whether this process is influenced by IV Fe and oral vitamin E administration. METHODS: Within four HD sessions, blood samples were taken from seven chronic HD patients at time 0 (before HD), 60, 70, and 130 min of HD session. Neutrophil respiratory burst was assessed by luminol-enhanced chemiluminescence (CL). Plasma advanced oxidation protein products (AOPP) concentration was measured spectrophotometrically. During the second and the fourth HD, 62.5 mg of sodium ferric gluconate was applied IV in the 65th minute of HD. Before the last two HD, the patients were given orally 200 mg of vitamin E daily for 7 days. Patient's results were compared with healthy controls. RESULTS: Predialysis CL is higher in patients than in controls (1,926 +/- 436 vs. 1,083 +/- 325 RLU, p<.01). CL decreases in the 60th min of HD (1,926 +/- 436 vs. 1,220 +/- 599 RLU, p<.05); thereafter, it remains stable. After Fe application, CL increases at time 130 compared with CL at time 60 (1,303 +/- 269 vs. 877 +/- 292 RLU, p<.05). AOPP concentration is higher in patients than in controls (137.5 +/- 42.7 vs. 88.9 +/- 24.8 micromol/L, p<.01) and remains unaffected by vitamin E supplementation. After vitamin E intake, predialysis CL remains significantly higher than in controls, and changes in CL during HD are minimal despite Fe administration. CONCLUSION: HD patients' neutrophils generate more oxygen radicals than in healthy individuals. This production decreases during HD and then increases after IV Fe administration. Short-term vitamin E administration attenuates this fluctuation of neutrophil oxidative metabolism, without affecting the total degree of oxidative stress.     

The effect of prostate cancer and antiandrogenic therapy on lipid peroxidation and antioxidant systems

In living organism, excessive free radicals or oxidative damage which occur as a result of deficient antioxidant defensive mechanisms by the effect of endogenous and exogenous factors, influences especially developmental steps of chemically induced cancers. In our study, plasma malondialdehyde level (MDA) as an indicator of lipid peroxidation, erythrocyte glutathione (GSH) level as an indicator of antioxidant state, glutathione reductase (GSH-Red), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) as an antioxidant enzymes and plasma vitamin E level were detected in patients with prostate cancer (21 males; age, 69.4 +/- 4.8 years) before and after three months of antiandrogenic therapy with goserelin acetate as luteinizing hormone releasing hormone (LHRH) analogue. Healthy people evaluated as a control group (20 males; age, 63.7 +/- 3.9). Erythrocyte GSH levels, the activities of GSH-Red and GSH-Px and plasma vitamin E levels were found significantly low in patients with prostate cancer when compared with the healthy subjects (p < 0.01, p < 0.05, p < or = 0.001 and p < or = 0.001 respectively). Plasma MDA level and erythrocyte GST activity of patient group were significantly higher than the levels of control group (p < or = 0.001 and p < or = 0.001 respectively). After antiandrogenic therapy erythrocyte GSH level, GSH-Red, GSH-Px activity and plasma vitamin E level were found unchanged. Significant decrease in plasma MDA level and significant increase in erythrocyte GST activity were detected in patient group (p < 0.05 and p < or = 0.01 respectively). The study has revealed the shift in the oxidant-antioxidant balance towards oxidative state in patients with metastatic prostate cancer. Our results showed that antiandrogenic therapy increased in GST activity, decreased in lipid peroxidation.     

Effects of large dose vitamin E supplementation on anemia in hemodialysis patients

In order to clarify the effect of vitamin E (alpha-tocopherol) on anemia and the osmotic fragility of red blood cells (RBC) plasma and RBC levels of vitamin E were measured in 30 regular dialysis patients before and after oral supplementation of vitamin E, 600 mg daily for 30 days. Plasma levels of vitamin E were in the normal range (10.67 +/- 0.85, 9.73 +/- 0.77 microgram/ml) but RBC levels in packed red cells were significantly lower than healthy controls (0.57 +/- 0.05, 0.45 +/- 0.07 microgram/ml). Oral supplementation of vitamin E increased both plasma (20.37 +/- 1.61 micrograms/ml) and RBC vitamin E (1.56 +/- 0.11 micrograms/ml) in packed red cells, while in unsupplemented patients, vitamin E levels remained unchanged. In patients receiving vitamin E, mean osmolarities at the beginning and end of hemolysis decreased from 102.8 +/- 0.9 to 98.9 +/- 0.7 and 72.1 +/- 1.1 to 67.4 +/- 0.8 mosm/l, respectively. In addition, the hematocrit increased from 26.1 +/- 1.0 to 28.1 +/- 1.2%. These changes are statistically significant (less than 0.05). In conclusion, the oral supplementation of vitamin E could be of clinical benefit in correcting anemia in regular dialysis patients by reducing the fragility of RBCs.     

Prevalence and determinants of hyperhomocysteinemia in hemodialysis and peritoneal dialysis

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for atherosclerotic complications in patients with end-stage renal disease, although the mechanisms remain unclear. The major determinants of plasma homocysteine concentration are usually folate, vitamin B12, pyridoxal 5'-phosphate (vitamin B6), and glomerular filtration rate. METHODS: We measured factors, including plasma folate, vitamin B12, vitamin B6, creatinine, as well as the dose and duration of dialysis, that might affect plasma homocysteine concentrations in 130 patients on hemodialysis (HD) and compared these observations with those in 46 patients on peritoneal dialysis (PD). Independent determinants of total homocysteine were identified using a multiple logistical regression analysis. RESULTS: Total homocysteine values averaged 29.8 mumol/liter in HD patients, significantly higher than the mean value of 19.9 mumol/liter observed in patients on PD (P < 0.001). The prevalence of hyperhomocysteinemia was 90.8% among HD patients, significantly higher than the prevalence of 67.4% among PD patients. Folate values in HD patients averaged 45.5 nmol/liter and were significantly lower than in PD patients (104.2 nmol/liter, P < 0.001). For patients on HD, the only determinant of total homocysteine concentration was plasma folate (r = -0.31, P < 0.001). In contrast, for PD patients, total homocysteine did not correlate with plasma folate, vitamin B12, or vitamin B6. CONCLUSIONS: Hyperhomocysteinemia is more prevalent and intense in HD patients compared with those on PD. The homocysteine response may become refractory to excess folate supplementation in PD patients.     

Effects of vitamin supplementation on microcirculatory disturbance in hemodialysis patients without peripheral arterial disease

AIMS: Dysfunctional endothelium caused by oxidative stress is thought to play a role in pathogenesis of a variety of conditions including atherosclerosis. We investigated whether a microcirculatory disturbance in hemodialysis (HD) patients was associated with increased oxidative stress and endothelial injury. PATIENTS AND METHODS: Transcutaneous oxygen tension (TcPO2) on the dorsum of the foot at rest was measured as a marker of microcirculation in 33 patients undergoing HD without clinical manifestations of peripheral arterial disease and 20 healthy controls. Furthermore, in order to examine whether TcPO2 was affected by antioxidants, oral supplementation with a combination of vitamin C (200 mg daily) and vitamin E (600 mg daily) was administered for 6 months to 8 patients with microcirculatory disturbance (TcPO2 values of 50 mmHg or less). Serum biochemical parameters including vitamins were also measured. RESULTS: Mean TcPO2 value was significantly lower in HD patients than in control subjects (47.9 +/- 13.5 mmHg versus 62.4 +/- 11.9 mmHg, p < 0.001). After vitamin supplementation, TcPO2 values remarkably increased (40.6 +/- 10.0 mmHg versus 57.4 +/- 6.5 mmHg, p < 0.005). Serum vitamin C and vitamin E levels increased significantly as well, while serum levels of thrombomodulin, a marker of endothelial injury, and thiobarbituric acid reactants, a marker of lipid peroxidation, were significantly decreased in comparison with those before supplementation. CONCLUSIONS: Our results suggest that the microcirculatory disturbance in HD patients seems to be associated with endothelial damage caused by oxidative stress. Combined supplementation with vitamin C and vitamin E may be of clinical benefit in improving the cutaneous microcirculation by reducing oxidative stress.     

25-Hydroxyvitamin D levels in prevalent Australian dialysis patients

Aim:   Vitamin D deficiency is a common problem in the general population. A high frequency of vitamin D deficiency in the pre-dialysis and dialysis populations has been observed overseas, but there is limited information regarding vitamin D levels in Australian dialysis patients.
Method:   We measured 25-hydroxyvitamin D levels in 120 haemodialysis (HD) and 31 peritoneal dialysis (PD) patients. We defined vitamin D deficiency as a level <50 nmol/L and insufficiency as a level of 50–74 nmol/L. We assessed for correlation between vitamin D levels and markers of bone and mineral metabolism, age, sex, dialysis type, dialysis duration, haemoglobin and erythropoietin dose.
Results:   Of the HD patients, 59 (49%) were frankly deficient and 39 (33%) had insufficiency. Of the PD patients, 24 (77%) were frankly deficient and 6 (19%) had insufficiency. Overall, only 23 patients (19%) had sufficient levels of vitamin D. Vitamin D levels were significantly lower in PD patients ( P  = 0.001), in females ( P  = 0.002) and in those with diabetic nephropathy ( P  = 0.03). There was no correlation between vitamin D levels and markers of bone and mineral metabolism, age, dialysis duration, haemoglobin or erythropoietin dose.
Conclusion:   Vitamin D deficiency and insufficiency were very common in this cohort of prevalent Australian dialysis patients. Lower levels were associated with PD as treatment modality, female sex and diabetic nephropathy.     

Brain natriuretic peptide and its relationship to left ventricular hypertrophy in patients on peritoneal dialysis or hemodialysis less than 3 years

An increase of brain natriuretic peptide (BNP) levels is commonly observed in patients on dialysis. Increased circulating levels of BNP are related to future cardiac events and associated with shorter survival in patients on chronic hemodialysis (HD). During the first 1 or 2 years on dialysis, patients on peritoneal dialysis (PD) have been shown to have an improvement in left ventricular hypertrophy, blood pressure, and volume status. This study compares BNP levels and cardiac status of PD and HD patients without cardiovascular disease and on dialysis for less than 36 months. The correlation between plasma BNP concentration and findings of echocardiography before HD scans were examined and compared with findings of PD. Twenty-two HD patients (15 men, 7 women; mean age, 52.5 +/- 13.9 years) and 19 PD patients (10 men, 9 women; mean age, 47.6 +/- 11.3 years) were studied. There were no significant differences between HD and PD patients with regard to age, gender, duration of dialysis, left ventricular mass, left ventricular mass index (p > 0.05). Plasma BNP levels were markedly greater in HD patients (467.8 +/- 466.5 pg/ mL) than those of PD patients (143.1 +/- 165.2 pg/mL). Urine output was significantly higher in PD patients compared with HD patients (p < 0.05). A positive correlation between systolic blood pressure, diastolic blood pressure, and plasma BNP in HD patients (r: 0.653, p: 0.001; r: 0.493, p: 0.023, respectively) was detected. Additional studies are needed to investigate whether lower BNP level in PD patients is an advantage.     

Changes in the prognosis for survival of patients with end-stage renal disease (ESRD) treated by hemodialysis

We started dialysis treatment in our institution in 1966, and have improved hemodialysis (HD) treatment through the induction of a biocompatible dialysis membrane, recombinant human erythropoietin, activated vitamin D and purification of the dialysate. We verified improvement of the prognosis for survival of patients with ESRD during this forty-year period, retrospectively. A total of 1,690 patients who began dialysis therapy in our hospital between January 1966 and December 2005 was studied (men: 1,047, women: 643, age: 58.6 +/- 17.4 years. They were divided into four groups (A: patients who started dialysis in the period from 1966 to 1975; n = 280, B: 1976-1985; n = 455, C: 1986-1995; n = 499, D: 1996-2005; n = 456). The mean follow-up period was 8.48 +/- 8.53 years. Of the patients 1,588 were treated with HD, 78 with peritoneal dialysis (PD), and 24 with PD or HD. Age at the initiation of dialysis increased gradually (A: 40.1 +/- 14.2 y-o, B: 53.2 +/- 15.8 y-o, C: 60.0 +/- 16.0 y-o, D: 66.4 +/- 13.8 y-o), and diabetics increased (A: 6.4%, B: 19.5%, C: 25.6%, D: 33.4%). A total of 1,180 patients died; 48.5% of these patients died of cardiovascular disease, 21.3% of infectious disease, and 6.4% of malignancy. Only 13 patients had kidney-transplants. With the Cox proportional hazard model for HD cases, age at the initiation of dialysis, gender, cause of renal disease, and the periods were significant predictors of mortality. The relative risk of mortality compared with that in A was reduced progressively: 0.796 in period B (95% confidence interval [CI]: 0.659-0.961, p = 0.0178), 0.505 in period C (95% CI: 0.409-0.623, p < 0.0001), and 0.286 in period D (95% CI: 0.223-0.366, p < 0.0001). CONCLUSIONS: Although the number of high-aged patients or diabetics with ESRD increased in these 40 years, the survival of the patients with ESRD improved.     

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.     

Infective endocarditis in maintenance hemodialysis patients: fifteen years' experience in one medical center

BACKGROUND: Infective endocarditis (IE) is a serious infectious condition, with high morbidity and mortality in hemodialysis (HD) patients. This study was undertaken to determine the IE risk factors in maintenance HD patients, and the mortality risk factors. METHODS: We retrospectively reviewed all IE cases of maintenance HD patients at our center over the past 15 yrs (the study group). Regular HD patients without IE in the same period were used as the control group. The basic data of the two groups were analyzed to determine IE risk factors in HD patients. The in-hospital parameters of survival and mortality in the study group patients were used for mortality risk factors analysis. RESULTS: There were 18 definite, and two possible, IE diagnoses in the study group and no cases in the 268 controls. There was no significant difference in age, sex, diabetes, hypertension, underlying malignancy, previous cerebral vascular accident (CVA) history, and calcium multiplied by phosphate product. There was a significant difference between the two groups (study group vs. controls) in pacemaker implant history (15 vs. 1.1%, p<0.01), previous heart surgery history (15 vs. 0.4%, p<0.01), congestive heart failure (CHF) (50 vs. 10.4%, p<0.05), duration on maintenance HD (12.9+/-19.1 vs. 57.9+/-42.3 months, p<0.001), serum albumin at the time of admission (2.91+/-0.40 vs. 3.96+/-0.52 g/dL, p<0.001). There were more patients dialyzed via non-cuffed dual-lumen catheters in the study group (55 vs. 0%, p<0.001), and fewer patients dialyzed via arteriovenous fistula (AVF) (25 vs. 87.7%, p<0.001). The mortality in HD patients with IE was high (60%), especially in patients with methicillin-resistant Staphylococcus aureus (MRSA) endocarditis (100%). The most common pathogen was S. aureus (n=12). MRSA was more common than methicillin-susceptible S. aureus (MSSA) (67 vs. 33%). Univariant analysis of in-hospital clinical parameters for mortality revealed no significant difference in age, diabetes, dual-lumen catheter implantation, serum albumin, time to diagnosis, and time to antibiotic use. Borderline statistical significance was noted in serum C-reactive protein (CRP) (p=0.051), and blood glucose level (p=0.056). There were more IE cases due to MRSA in the mortality group than in the survival group (8 vs. 0 cases, p=0.013), but fewer cases due to MSSA (0 vs. 4 cases, p=0.050). CONCLUSIONS: IE should be considered in HD patients with the following risk factors, which include previous heart surgery or pacemaker implantation, shorter HD duration, and especially for patients dialyzed via dual-lumen catheters. The in-hospital clinical parameters including CRP and blood sugar level can offer information concerning prognosis. Since MRSA has increased in recent years and is associated with high mortality, strategies for prevention and treatment require development.     

Oxidative stress markers in hepatitis C infected hemodialysis patients

BACKGROUND: Oxidative stress in hemodialysis (HD) patients or hepatitis C virus (HCV) infections may be related to increased production of free radicals. We assessed the effect of HCV infection on the oxidative stress markers, malondialdehyde (as TBARS), protein carbonyl content and protein sulfhydryl groups, in chronic HD patients. METHODS: Twenty HCV infected patients (9 men and 11 women, age 44.8 +/- 14.3 years) and 10 non-HCV infected patients (6 men and 4 women, age 55.6 +/- 14.3 years) receiving regular HD were recruited. The average hemodialysis duration was 30 +/- 8 months for HCV (+) patients and 14 +/- 8 months for HCV (-) patients. Controls consisted of healthy subjects. RESULTS: Serum TBARS and carbonyl content were significantly elevated in HCV(-) patients (p<0.001, p<0.05) and in HCV(+) patients (p<0.001, p<0.001) vs. Controls. There was also a significant difference in serum TBARS and carbonyl content between HCV(-) patients and HCV(+) patients (p<0.001, p<0.05). Serum protein sulfhydryl groups in HCV(-) and HCV(+) patients were the same, but significantly lower than in Controls (p<0.001, p<0.001). When HCV(+) patients were divided into two sub-groups, one with shorter (13.4 +/- 8 months; n=7) and the other with longer (40.3 +/- 8 months; n=13) duration of HD treatment, no differences were found between subgroups. CONCLUSION: HCV infection may aggravate oxidative stress in HD patients.     

Cystatin C as marker of residual renal function in patients on peritoneal dialysis: relation with parameters of peritoneal function

INTRODUCTION: Cystatin C (CysC) is a nonglycosylated protein of low molecular weight not influenced by age, sex or inflammation. The aim of this paper is to ascertain the usefulness of serum CysC level determination in peritoneal dialysis (PD) patients. MATERIAL AND METHODS: CysC serum levels were determined in 80 PD patients. The mean age of patients was 53.7 +/- 15 years, with 15.3 +/- 25.8 months on PD. Thirty-three percent were on continuous ambulatory peritoneal dialysis (CAPD) and 66.3% on automated peritoneal dialysis (APD). Fourteen patients (17%) had no residual renal function (RRF). RESULTS: Mean CysC levels were 5.8 +/- 1.4 mg/L, without differences between men (5.5 +/- 1.4 mg/L) and women (5.6 +/- 1.5 mg/L, NS). There was no correlation between CysC levels and age, weight, height or time on PD. Anuric patients had CysC levels significantly higher than non-anuric (6.7 +/- 1.4 vs. 5.3 +/- 1.3 mg/L, p<0.001). CysC levels showed an inverse correlation with RRF (r=-0.60, p<0.001) and residual urine volume (r=-0.58, p<0.001). CONCLUSIONS: In conclusion, serum CysC levels had the same statistical significance as plasma creatinine levels, and they are not influenced by peritoneal transport in PD patients. Consequently, both parameters are valid RRF markers.     

Study of the homocysteine status in children with chronic renal failure

BACKGROUND/AIMS: Vascular diseases are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients and they cannot be explained entirely by the prevalence of traditional risk factors for atherosclerosis. The role of hyperhomocysteinemia as an additional risk factor in the development of accelerated atherosclerosis and/or thrombosis in these patients has been suggested possibly due to homocysteine (Hcy) induced endothelial cell injury. This study was aimed at evaluation of the Hcy status in children with chronic renal failure (CRF) especially in those suffering from ESRD and the possible role of folic acid and vitamin B12 therapy in the correction of hyperhomocysteinemia if present. METHODS: This study included 40 patients with CRF, 30 on regular hemodialysis (HD) treatment (group I) and 10 on conservative (medical) treatment (group II) in comparison to 20 healthy age- and sex-matched controls (group III). The basal serum levels of Hcy, folic acid and vitamin B12 as well as plasma level of activated protein C resistance (APC-R) were measured in patients and controls. RESULTS: The mean serum Hcy was significantly higher in those on regular HD (17.9 +/- 10.07 micromol/l) in comparison to those on conservative treatment (8.05 +/- 2.99 micromol/l) (p < 0.001) and controls (7.07 +/- 2.24 micromol/l) (p < 0.001), while there was no significant variation between the latter two groups. The mean values of APC-R, folic acid and vitamin B12 failed to show any significant difference in the three studied groups. No significant difference in the basal Hcy level between patients with previous history of vaso-occlusive disease and those without was found. Half of the patients on regular HD (group Ia) (n = 15) were given folic acid as 50 mg of 5-formyl-tetrahydrofolate (the active form of folic acid) intravenously once weekly after the dialysis session for 4 weeks. The other half (group Ib) (n = 15) received in addition to folic acid therapy, vitamin B12 1,000 microg hydroxycobalamine once intramuscularly. After therapy the mean Hcy decreased significantly in those who received folic acid and vitamin B12 (7.80 +/- 3.77 micromol/l) (p < 0.001) to a level comparable to the basal levels in conservative and control groups, whereas a non-significant decrease was found in those who received folic acid only (13.3 +/- 11.47 micromol/l) (p > 0.05). CONCLUSIONS: Hcy is high in children with ESRD on regular HD and combined therapy of the active form of folic acid and vitamin B12 is of value in decreasing Hcy values comparable to that in controls.