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.     

Relationships between brain natriuretic peptide, troponin I and QT dispersion in asymptomatic dialysis patients

OBJECTIVES: The relationships between increased wall stress, myocyte death, and ventricular repolarization instability in patients with heart failure were reported. DESIGN AND METHODS: The relationships between brain natriuretic peptide (BNP), a predictor of increased wall stress of hearth; troponin I (cTnI), a predictor of myocyte death; and QT dispersion (QTd), a reflection of ventricular repolarization instability were evaluated in age- and sex-matched asymptomatic 29 hemodialysis (HD) patients and 26 peritoneal dialysis (PD) patients, and the finding were compared. RESULTS: Serum BNP and cTnI levels in HD patients (722.9 +/- 907.9 pg/mL, 0.05 +/- 0.07 microg/L, respectively), just before HD, were significantly higher than those of PD patients (255.4 +/- 463.7 pg/mL, 0.02 +/- 0.02 microg/L, respectively; p < 0.05). There was no significant difference between groups with regard to corrected QTd and maximum and minimum QT intervals (p > 0.05). Serum cTnI levels were significantly and positively correlated with serum BNP levels in both dialysis groups (r = 0.447, p = 0.048). No relationship was found between plasma BNP and ECG parameters studied in both groups (p > 0.05). CONCLUSION: Increased serum cTnI levels were associated with elevated BNP levels in both dialysis groups. The increases in BNP and troponin I are more likely to reflect hypervolemia. Although CAPD patients were receiving dialysis daily and HD patients were more hypervolemic, CAPD patients have similar QTdc and accordingly a similar tendency toward arrhythmias. This suggests that factors other than electromechanical interaction may be important in determining the QT interval length in patients on dialysis.     

Clinical significance of natriuretic peptides and cyclic GMP in hemodialysis patients with coronary artery disease

BACKGROUND: Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP) are suitable markers of 'dry body weight' (DW) in hemodialysis (HD) patients. However, it is still unknown whether these markers can be applied to patients with renal failure and coronary artery disease (CAD). We examined the reliability of these peptides as volume markers in HD patients with CAD. We also assessed the relationship between natriuretic peptides and indices of left ventricular (LV) function. METHODS: Plasma concentrations of ANP, BNP and cGMP were determined before and after HD in patients with CAD (group 1, n = 19, mean age 63 +/- 12 years) and were compared with those of patients without cardiac disease (group 2, n = 20, age 61 +/- 15 years). Using data obtained by cardiac catheterization, we examined the relationship between natriuretic peptides and indices of LV function in HD patients with CAD. RESULTS: Baseline ANP (244 +/- 205 pg/ml), BNP (713 +/- 928 pg/ml) and cGMP (29.6 +/- 21.6 pmol/ml) were significantly higher in group 1 than in 11 healthy volunteers (18.6 +/- 9.9 pg/ml, 7.7 +/- 7.6 pg/ml, cGMP 8.9 +/- 4.9 pmol/ml, respectively). HD significantly reduced plasma ANP (87 +/- 75 pg/ml) and BNP (477 +/- 702 pg/ml) although they were still above normal control. HD reduced plasma cGMP (7.2 +/- 4.5 pmol/ml) to normal values, suggesting the elimination of cGMP across the dialyzers. Baseline levels of ANP, BNP and cGMP in group 2 were less than those of group 1 but higher than the control. HD reduced natriuretic peptides in group 2 to levels lower than those in post-HD group 1. After HD, there was no significant correlation between reductions in body weight and changes in ANP or BNP. Baseline ANP and BNP levels closely correlated with pulmonary artery pressure, pulmonary artery wedge pressure, left ventricular end-diastolic pressure and left ventricular ejection fraction. A significant correlation was observed between BNP levels and the severity of CAD. CONCLUSION: ANP, BNP and cGMP seem to be a useful markers for fluid overload but not for DW in HD patients with CAD. Plasma ANP and BNP might be useful markers for left ventricular function.     

The prognostic role of brain natriuretic peptides in hemodialysis patients

BACKGROUND: Although plasma concentrations of brain natriuretic peptides (BNP) increase in hemodialysis (HD) patients as well as patients with cardiovascular diseases (CD), the clinical significance of BNP in HD patients has yet to be elucidated. In this study, we investigated the pathophysiological significance of BNP in HD patients. METHODS: Plasma BNP concentrations were measured in 164 HD patients after HD and 14 healthy volunteers. In 12 patients without CD, BNP was also measured before HD. Multiple regression analysis was performed to determine the important factors causing increased plasma BNP concentrations. Cardiac mortality was monitored for 36 months after baseline analysis, and the prognostic role of BNP was examined by Cox proportional hazards regression analysis. RESULTS: Plasma BNP concentrations of HD patients without CD decreased significantly during HD session (124.5 +/- 90.7 vs. 91.4 +/- 67.6 pg/ml, mean +/- SD, p = 0.004), but were still significantly higher than those of the healthy subjects (9.7 +/- 9.2 pg/ml, p = 0.0002). Plasma BNP concentrations of patients with CD were significantly higher than of those without CD (579.6 +/- 564.3 vs. 204.0 +/- 241.5 pg/ml, p < 0.0001). Plasma BNP concentrations were also significantly higher in diabetes mellitus (DM) patients than in non-DM patients (514.1 +/- 585.4 vs. 296.0 +/- 347.0 pg/ml, p = 0.0031). Multiple regression analysis showed that left ventricular mass index (LVMI), CD and DM were independent factors for the elevated BNP (R(2) = 0.303, p < 0.0001). During a 36-month follow-up period, cardiac death occurred in 13 patients. Kaplan-Meier survival estimates of patients from varying plasma BNP quartiles (<200, 200-450, 450-700 and >700 pg/ml) differed between the four groups (p < 0.0001). The group with the highest BNP level (>700 pg/ml) had the lowest survival. When compared with patients with BNP <200, the hazard ratios for cardiac death of patients with BNP of 200-450, 450-700 and >700 pg/ml were 2.3 [95% confidence interval (CI) 0.14-36.7], 18.7 (1.9-183.4) and 51.9 (6.5-416.3), respectively. The univariate Cox proportional hazards model showed that BNP, left ventricular ejection fraction, LVMI, age, DM, serum albumin and C-reactive protein (CRP) were significantly associated with the risk of cardiac mortality. By stepwise multivariate Cox proportional hazards analysis, only BNP, LVMI and CRP remained powerful independent predictors of cardiac death. The relative risk ratios were 1.002 (95% CI 1.001-1.002) for BNP, 2.192 (1.532-3.135) for CRP and 1.027 (1.013-1.042) for LVMI. CONCLUSION: High plasma BNP concentrations in HD patients were associated with volume overload, left ventricular hypertrophy, CD and DM. Plasma BNP concentration may be a useful parameter for assessing the risk of cardiac death in HD patients by providing prognostic information independently of other variables previously reported.     

Possible involvement of TNF-alpha in left ventricular remodeling in hemodialysis patients

BACKGROUND: Tumor necrosis factor (TNF)-alpha causes hypertrophic as well as negative inotropic effects on cardiac myocytes. Circulating TNF-alpha levels are reported to be elevated in end-stage renal disease (ESRD) patients undergoing maintenance hemodialysis (HD). We investigated whether increased circulating TNF-alpha is associated with left ventricular remodeling against pressure and/or volume overload in HD patients with or without diabetes mellitus. METHODS: Echocardiography and the measurement of plasma TNF-alpha and B-type natriuretic peptide (BNP) concentrations, one of the parameters indicating left ventricular wall stress, were performed on 176 ESRD patients undergoing maintenance HD (88 non-diabetic and 88 diabetic patients). RESULTS: The mean plasma TNF-alpha concentrations were high, but did not differ between non-diabetic and diabetic patients (9.8 +/- 4.3 pg/mL vs. 9.9 +/- 5.4 pg/mL). In non-diabetic patients, plasma TNF-alpha concentration correlated positively with interventricular septal wall thickness (IVST) and relative left ventricular wall thickness (rLVWT), and inversely with left intraventricular dimensions, but did not correlate with left ventricular mass index (LVMI). In contrast, in diabetic patients, plasma TNF-alpha concentration correlated positively with plasma BNP concentration (r=0.821, p=0.0001) and left intraventricular dimensions, and inversely with rLVWT (r=-0.407, p=0.0001) and left ventricular fractional shortening (r=-0.445, p=0.0001). CONCLUSIONS: Circulating TNF-alpha is possibly involved in concentric left ventricular remodeling in non-diabetic HD patients, whereas it is associated with eccentric left ventricular remodeling against sustained pressure and/or volume overload in diabetic HD patients.     

Changes in B-type natriuretic peptide levels in hemodialysis and the effect of depressed left ventricular function

B-type natriuretic peptide (BNP) is a cardiac neurohormone specifically secreted by the cardiac ventricles in response to volume expansion, pressure overload, and resultant increased wall tension. Previous research has shown elevated BNP levels in patients with volume overload caused by end-stage renal disease (ESRD). This pilot study was designed to describe the relative reduction in BNP that occurs as a result of hemodialysis (HD) in relation to baseline left ventricular function. Hemodialysis patients (n = 34) with ESRD were enrolled in a prospective manner. All patients had blinded serum BNP levels measured at the initiation and termination of HD. Levels of BNP were also measured in the dialysate and any residual urine, if available. In addition, monthly urea reduction ratio (URR) and Kt/V were obtained. The most recent measurement of left ventricular ejection fraction (LVEF) by any method was obtained from chart review. The BNP reduction ratio (BNPRR) was calculated by the following expression: pre-BNP-post-BNP/pre-BNP. The mean age was 50.8 years, 50.0% were male, and 55.9% were African American. A mean of 3239.4 mL of fluid was removed during HD. The mean pre-BNP, post-BNP, and change in BNP were 556.3 +/- 451.5 pg/mL, 538.6 +/- 488.3 pg/mL, and -17.6 +/-147.0 pg/mL. Of the 27 patients who had both pre-BNP and post-BNP values in the measurable range (< 1,300 pg/mL), BNP rose in 9 (33.3%) and fell in 18 (66.7%). The BNPRR had the following correlations: volume removed, r = -0.33, P = .07; Kt/V, r = -0.51, P = .01; URR, r = -0.34, P = .09; and change in body weight, r = -0.33, P = .07. The BNPRR was not correlated with time on dialysis or change in blood pressure. A total of 20 patients had LVEF recorded and post-BNP levels in the measurable range. For this group, the BNPRR values stratified by lowest to highest LVEF group were 4.6%, 19.1%, and 21.8%; P = .95 for trend. The BNP values were elevated in ESRD patients and decreased slightly during HD. This change was more pronounced in patients with normal or mildly impaired LVEF. The BNPRR correlated with the volume removed, change in body weight, and Kt/V. Future research with the BNPRR as a potential marker of the adequacy of volume removal in HD is warranted.     

Cinacalcet is efficacious in pediatric dialysis patients

Secondary hyperparathyroidism (high-turnover bone disease, or HTBD) is manifested by elevated parathyroid hormone (PTH) levels. Control of HTBD may be achieved by maintaining low serum phosphorous levels and administering vitamin D therapy, although some patients continue to exhibit high PTH levels. We report the results of the efficacy of the calcimimetic cinacalcet in six hemodialysis (HD) and three peritoneal dialysis (PD) pediatric patients with HTBD, age 14.5 +/- 1.0 (range 7.5-17.5) years. Six patients received 30 mg/day, one required 60 mg/day, and two received 120 mg/day. Treatment with cinacalcet resulted in a 61% decline in intact PTH (iPTH) levels (1,070 +/- 171.5 pretreatment to 417.6 +/- 97.8 posttreatment pg/ml, p = 0.005). Serum alkaline phosphatase also declined (561.8 +/- 169.6 U/L pretreatment to 390.3 +/- 110.3 U/L posttreatment pg/ml). During therapy, serum calcium (p = 0.9) and phosphorous (p = 0.9) levels, calcium-phosphorous product (p = 0.8), systolic blood pressure (BP) (p = 1.0), diastolic BP (p = 0.8), and hemoglobin (p = 0.9) remained unchanged. The dose of oral calcitriol for the three patients on PD while receiving cinacalcet trended downward (0.8 +/- 0.2 pretreatment vs. 0.5 +/- 0.0 mug/day posttreatment pg/ml), as did the dose of paracalcitol for those receiving HD (6.6 +/- 2.3 pretreatment vs. 4.3 +/- 1.7 micrograms/day posttreatment pg/ml). We conclude that short-term treatment with the calcimimetic cinacalcet is efficacious in adolescent dialysis patients.     

An association between inflammatory state and left ventricular hypertrophy in hemodialysis patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1beta, IL-6, TNF-alpha, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r=0.556, p=0.001), diastolic BP (r=0.474, p=0.004), and serum levels of TNF-alpha (r=0.446, p=0.009). Multiple regression analysis showed that systolic BP and TNF-alpha levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 +/- 8.7 vs. 7.3 +/- 0.7 pg/ mL, p=0.001). Predialysis serum levels of TNF-alpha in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 +/- 3 vs. 7 +/- 1.45 pg/mL, respectively, p>0.05). However, serum levels of IL-6 and TNF-alpha significantly elevated after HD, when compared to predialysis levels (from 15.7 +/- 8.7 to 17.8 +/- 9.5 pg/mL, p=0.001 and from 8.3 +/- 3.0 to 9.9 +/- 3.5 pg/mL p=0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-alpha in particular, seem to be associated with LVH in ESRD patients.     

Platelet activity and serum homocysteine levels in patients with end-stage renal failure with regard to dialysis modality

BACKGROUND: Recent evidence suggests that the activation of platelets and their interaction with circulating cells are important independent risk factors for atherosclerosis. In non-uremic patients with symptomatic peripheral vascular disease, a relationship between serum homocysteine (Hcy) levels and platelet activity had been reported. The purposes of this study were to evaluate of effects of dialysis modality on platelet activity in patients with end-stage renal failure and to investigate the relationship between platelet activity, Hcy, and left ventricular hypertrophy (LVH). MATERIAL AND METHODS: In age and sex matched 19 healthy subjects, 20 hemodialysis (HD) patients, and 18 continuous ambulatory peritoneal dialysis (CAPD) patients, the expression of platelet surface receptors CD41, CD61, CD42a, and CD62P were investigated. CD62P expression was statistically significantly increased in HD patients compared with CAPD patients and controls (34.4 +/- 22.5%; 17.3 +/- 19.6%, 12.0 +/- 15.6%, respectively, p < 0.05), but not in CAPD patients compared with controls. There was a positive correlation between CD62 expression and duration of dialysis in HD patients (r = 0.498, p = 0.026). Mean plasma Hcy levels in dialysis patients were higher than reference levels. However, we could not find any relationship between CD62 expression, Hcy, and LVH in both groups (p > 0.05). CONCLUSIONS: Hemodialysis and peritoneal dialysis (PD) have a different impact on the expression of CD62: peritoneal dialysis seems to have a more favorable effect. It may be possible that the differences in biocompatibility between PD and HD potentially contribute to differences in CD62 expression.     

Relationships between Brain Natriuretic Peptide,Troponin I and QT Dispersion in Asymptomatic Dialysis Patients

Objectives. The relationships between increased wall stress, myocyte death, and ventricular repolarization instability in patients with heart failure were reported. Design and Methods. The relationships between brain natriuretic peptide (BNP), a predictor of increased wall stress of hearth; troponin I (cTnI), a predictor of myocyte death; and QT dispersion (QT_d), a reflection of ventricular repolarization instability were evaluated in age- and sex-matched asymptomatic 29 hemodialysis (HD) patients and 26 peritoneal dialysis (PD) patients, and the finding were compared. Results. Serum BNP and cTnI levels in HD patients (722.9 ± 907.9 pg/mL, 0.05 ± 0.07 μg/L, respectively), just before HD, were significantly higher than those of PD patients (255.4 ± 463.7 pg/mL, 0.02 ± 0.02 μg/L, respectively; p < 0.05). There was no significant difference between groups with regard to corrected QT_d and maximum and minimum QT intervals (p > 0.05). Serum cTnI levels were significantly and positively correlated with serum BNP levels in both dialysis groups (r = 0.447, p = 0.048). No relationship was found between plasma BNP and ECG parameters studied in both groups (p > 0.05). Conclusion. Increased serum cTnI levels were associated with elevated BNP levels in both dialysis groups. The increases in BNP and troponin I are more likely to reflect hypervolemia. Although CAPD patients were receiving dialysis daily and HD patients were more hypervolemic, CAPD patients have similar QT_dc and accordingly a similar tendency toward arrhythmias. This suggests that factors other than electromechanical interaction may be important in determining the QT interval length in patients on dialysis.     

Effect of sympathetic and plasma renin activity on hemodialysis hypertension

BACKGROUND: The reasons for poor control of blood pressure in hemodialysis (HD) patients are not clear, while patients have achieved their desirable dry weight and excess weight are not different between the hypertensive and normotensive patients. A link between sympathetic activity and HD hypertension could be an alternative explanation. PATIENTS AND METHODS: We studied the effect of sympathetic and plasma renin-aldosterone activity of 10 hypertensive patients, 5 men and 5 women, aged from 30 to 60 years. The results were compared to those of another 10 normotensive hemodialysis patients. Blood samples were taken before HD and at the end of a 4-hour HD session for plasma aldosterone (ALDO), renin activity (PRA), adrenaline and noradrenaline determination. One month dialysis records, which includes 13 dialysis sessions and 26 blood pressure readings for each patient were used, for pre-dialysis and post dialysis mean arterial blood pressure (MAP) measurement. RESULTS: Pre-dialysis plasma adrenaline was 124.12 +/- 12.93 pg/ml vs. 121.12 +/- 14.71 pg/ml and plasma noradrenaline was 260.88 +/- 140.86 pg/ml vs. 138.11 +/- 122 +/- 32 pg/ml for hypertensive and normotensive patients, respectively. Post-dialysis plasma adrenaline and noradrenaline levels were 119.37 +/- 8.81 pg/ml vs. 120.62 +/- 15.35 pg/ml and 210.44 +/- 126.71 pg/ml vs. 94.88 +/- 64.05 pg/ml for hypertensive and normotensive patients, respectively. Pre-dialysis PRA was 8.70 +/- 6.37 ng/ml/h vs. 2.77 +/- 1.8 ng/ml/h and plasma ALDO was 457.07 +/- 245.54 pg/ml vs. 197.74 +/- 87.46 pg/ml for hypertensive and normotensive patients, respectively. Pre-MAP was 109.76 +/- 5.21 mmHg vs. 99.28 +/- 7.13 mmHg and post-MAP was 107.22 +/- 6.74 mmHg, vs. 91.61 +/- 7.27 mmHg for hypertensive and normotensive patients, respectively. Plasma ALDO and fluid volume removed by ultrafiltration were found to be significantly correlated (p < 0.05). PRA and plasma adrenaline-noradrenaline levels were not correlated with MAP or body weight alterations. CONCLUSIONS: It is suggested that sympathetic activity, as it was expressed by plasma catecholamine alterations, is not associated with hemodialysis hypertension.     

Effect of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on peritoneal dialysis and hemodialysis

BACKGROUND: Several medications have been tested with the aim of decreasing oxidative stress and erythrocyte osmotic fragility in patients on dialysis. The aim of the present study was to assess the influence of vitamin E therapy on oxidative stress and erythrocyte osmotic fragility in patients on hemodialysis (HD) and peritoneal dialysis (PD). METHODS: This was a placebo-controlled study. The study was performed on 34 HD patients, 13 PD patients and 22 healthy volunteers with a mean age of 45.57 +/- 8.54 years. HD patients were divided into 2 groups: treatment (n=19) and control (n=15). Vitamin E was administered, 300 mg/day, to the HD treatment group and PD patients for 20 weeks. Lipid peroxidation, antioxidant condition and erythrocyte osmotic fragility (EOF) were examined before and after treatment. RESULTS: Before the treatment, the levels of EOF (p<0.001) and malondialdehyde (MDA) (p<0.001) were significantly lower, and erythrocyte superoxide dismutase (SOD) (p=0.001) and vitamin E levels (p<0.001) were significantly higher in the healthy group than PD and HD groups. Serum vitamin E increased from 0.93 +/- 0.16 to 1.09 +/- 0.14 mg/dL (p=0.001), EOF decreased from 0.49% +/- 0.03% to 0.42% +/- 0.04% NaCl (p<0.001), and plasma MDA values decreased from 2.77 +/- 0.87 to 2.20 +/- 0.767 nmol/mL (p=0.018) in the HD treatment group after vitamin E treatment. Levels of EOF decreased from 0.51% +/- 0.09% to 0.43% +/- 0.03% NaCl in the PD treatment group after vitamin E treatment (p=0.021). CONCLUSION: Vitamin E therapy is effective in decreasing the levels of EOF in patients on HD and PD, and it is also effective in decreasing lipid peroxidation in patients on HD.     

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.     

Interest of the brain natriuretic peptide as a marker of acute cor pulmonale in acute respiratory distress syndrome

OBJECTIVE: The aim of this study was to evaluate the accuracy of the BNP as a marker of acute cor pulmonale in patients with ARDS. STUDY DESIGN: Prospective clinical trial. PATIENTS AND METHODS: At day 2 or 3 after the onset of the ARDS, an echocardiography was performed. Patients with left ventricular dysfunction were excluded. Right ventricular area (RVA) and RVA/LVA ratio were measured. ACP was defined as RVA/LVA > 0.6 associated with septal dyskinesia. Simultaneously, 5 ml of blood was collected for BNP measurement. RESULTS: 26 patients were studied. BNP levels were higher in 10 patients with ACP: 585.5 [189-4830] vs 145.5 [36.5-346] pg/ml (P=0.01) but in those with creatinine clearance < 90 ml/min: 602 [331-3530] vs 125 [39-189] pg/ml (P=0.007). BNP was correlated with RVA (r=0.5; p=0.01), RVA/LVA ratio (r=0.61; p=0.001), sPAP (r=0.58; p=0.002) and with age, cardiac index and creatinine clearance (r=0.61; p=0.001). In multivariate analysis, BNP was only correlated with creatinine clearance (p=0.03), and RVA (p=0.06). CONCLUSION: In ARDS patients without left ventricular dysfunction, BNP level is more elevated in patients with acute cor pulmonale than patients without cor pulmonale.     

Timely transfer of peritoneal dialysis patients to hemodialysis improves survival rates

AIMS: The two main renal replacement therapies (RRT)--hemodialysis (HD) and peritoneal dialysis (PD)--have been considered to be antagonistic in most published studies on the clinical outcomes of dialysis patients. Recently, it has been suggested that the complementary use of both modalities as an integrated care (IC) strategy might improve the survival rate of end-stage renal disease patients. The aim of this study was to estimate the final clinical outcome of PD patients when they transfer to HD because of complications related to PD. MATERIALS AND METHODS: We retrospectively analyzed data from the following patients that started RRT during the last 10 years: 33 PD patients (IC group; age 55 +/- 15 years, mean +/- SD) who transferred to HD, 134 PD patients (PD group, age 64 +/- 11 years) who remained in PD, and 132 HD patients (HD group, age 48 +/- 16 years) who started and continued in HD. The main reasons for the transfer to HD were relapsed peritonitis and loss of ultrafiltration, while various comorbid risk factors were adjusted by Cox hazards regression model (age, presence of diabetes or/and cardiovascular disease, serum hemoglobin and albumin levels, as well as the modality per se). RESULTS: 3- and 5-year survival rates for the IC, PD and HD groups were 97% and 81%, 54% and 28%, and 92% and 83%, respectively. The 5-year survival rate was significantly higher in IC patients than in PD patients (p < 0.00001) but, was not different from that in HD patients. CONCLUSIONS: Our results show that the IC of dialysis patients undergoing RRT improves the survival of patients on PD if they are transferred to HD upon the appearance of PD related complications.     

Brain natriuretic peptide and P wave duration in dialysis patients

Objectives P wave duration and dispersion, defined as the difference between the maximum and minimum P duration, are regarded as very important non-invasive ECG markers for assessing atrial arrhythmia risk. Plasma brain natriuretic peptide (BNP) level is an independent predictor of recurrence of atrial fibrillation. We compared the effects of hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) on P wave duration, P dispersion, and BNP in end-stage renal disease (ESRD) patients and examined the relationship between BNP levels, P wave duration, and P dispersion. Design and methods Age-matched 22 HD patients (mean age 52.3 ± 14.0 years) and 19 CAPD patients (mean age 46.7 ± 10.9 years) were studied. Results BNP levels were greater in HD patients before the HD session (459.0 ± 465.1 pg mL⁻¹) than in CAPD patients (139.0 ± 170.1 pg mL⁻¹). The maximum and minimum P duration, and P dispersion, were similar for both groups (P > 0.05). Whereas BNP levels were negatively related to minimum P duration (r = −0.518, P = 0.019), BNP levels were positively correlated with systolic blood pressure and diastolic blood pressure (r = 0.672, P = 0.001 and r = 0.497, P = 0.022, respectively) in HD patients. Conclusions Whereas BNP levels are higher in HD patients when they are at peak-volume status, just before HD, P wave duration and P dispersion were similar for both groups. A negative relationship was detected between BNP levels and minimum P duration in HD patients. Expansion of extra-cellular volume causing myocardial stretching may be the principal cause of increased BNP in HD patients. A functional relationship between BNP and the P wave was not found. Additional studies are needed to evaluate the effect of BNP on the P wave.     

Stimulated IFNgamma and IL-10 secretion of blood mononuclear cells in patients on renal replacement therapies show different secretion patterns

Infection is still a leading cause of morbidity and mortality in patients on renal replacement therapy (RRT). Although the role of the immune system is of great importance, little is known about the influence of the mode of RRT to the preferential excretions of regulator cytokines of mononuclear cells. Therefore, we investigated the stimulated IFNgamma (Th1) and IL-10 (Th2) secretions of mononuclear cells from patients on RRT. Blood was drawn from 10 controls, 15 patients on hemodialysis (HD), 15 on peritoneal dialysis (PD), and 10 after kidney transplantation (Tx). The cells were separated, and phytohemagglutinine (PHA) was added for stimulation. After 0, 6, and 24 h, IFNgamma and IL-10 (pg/ml) were measured by enzyme-linked immunosorbent assay. IFNgamma secretion was significantly enhanced 6 (p < 0.001) and 24 h (p = 0.002) after stimulation in all groups (in mean +/- SEM). The analysis of the subgroups 6 h after adding PHA showed significant differences (p = 0.0239) with the lowest IFNgamma in Tx (16 +/- 5) and the highest in PD (79 +/- 30). For IL-10, secretion was enhanced in all groups 6 h after stimulation (p < 0.0116). The lowest secretions were seen in HD (18 +/- 8) and controls (27 +/- 9); the highest secretions were in Tx (98 +/- 20) and PD (57 +/- 12). The differences between HD and Tx (p < 0.01) and HD versus PD (p = 0.05) were significant. The stimulated cytokine secretion of blood mononuclear cells is preserved with RRT. The modes of RRT could influence the pattern of cytokine secretion. Surprisingly, the cells from patients on PD showed enhanced IL-10 secretion compared to HD. Presumably, this is due to the chronic contact of peritoneal dialysis fluids with monocytes and the lymphatic system in PD.     

B-type natriuretic peptide (BNP) and N-terminal-proBNP for heart failure diagnosis in shock or acute respiratory distress

BACKGROUND: Plasma B-type natriuretic peptide (BNP) assay is recommended as a diagnostic tool in emergency-room patients with acute dyspnea. In the intensive care unit (ICU), the utility of this peptide remains a matter of debate. The objectives of this study were to determine whether cut-off values for BNP and N-terminal-proBNP (NT-proBNP) reliably diagnosed right and/or left ventricular failure in patients with shock or acute respiratory distress, and whether non-cardiac factors led to an increase in these markers. METHODS: Plasma BNP and NT-proBNP levels and echocardiographic parameters of cardiac dysfunction were determined in 41 patients within 24 h of the onset of shock or acute respiratory distress. RESULTS: BNP and NT-proBNP levels were higher in the 25 patients with heart failure than in the other 16 patients: 491.7 +/- 418 pg/ml vs. 144.3 +/- 128 pg/ml and 2874.4 +/- 2929 pg/ml vs. 762.7 +/- 1128 pg/ml, respectively (P < 0.05). In the diagnosis of cardiac dysfunction, BNP > 221 pg/ml and NT-proBNP > 443 pg/ml had 68% and 84% sensitivity, respectively, and 88% and 75% specificity, respectively, but there was a substantial overlap of BNP and NT-proBNP values between patients with and without heart failure. BNP and NT-proBNP were elevated, but not significantly, in patients with isolated right ventricular dysfunction. Patients with renal dysfunction and normal heart function had significantly higher levels of BNP (258.6 +/- 144 pg/ml vs. 92.4 +/- 84 pg/ml) and NT-proBNP (2049 +/- 1320 pg/ml vs. 118 +/- 104 pg/ml) than patients without renal dysfunction. CONCLUSION: Both BNP and NT-proBNP can help in the diagnosis of cardiac dysfunction in ICU patients, but cannot replace echocardiography. An elevated BNP or NT-proBNP level merely indicates the presence of a 'cardiorenal distress' and should prompt further investigation.     

Associations between apolipoprotein E gene polymorphism and plasminogen activator inhibitor-1 and atherogenic lipid profile in dialysis patients

BACKGROUND: Apolipoprotein-E (ApoE) gene polymorphism has an important role in lipoprotein metabolism and could participate in the development of cardiovascular diseases (CVD). Plasminogen activator inhibitor-1 (PAI-1) is also regarded as a risk factor for CVD. The aim of the present study is to further investigate the possible link(s) between ApoE gene polymorphism and plasma PAI-1 antigen and serum lipid profile in peritoneal dialysis (PD) and hemodialysis (HD) patients. MATERIAL AND METHODS: We studied 72 PD patients (38 female, mean age 49.9 +/- 16.1 years), 72 HD patients (22 female, mean age 57.4 +/- 14.6 years), and 42 healthy subjects (21 female, mean age 50.1 +/- 18.6 years). Serum lipid parameters, plasma PAI-1 levels, and ApoE genotypes were determined in all subjects. RESULTS: The distribution of ApoE genotypes and alleles frequencies was similar in dialysis patients and healthy controls. In PD patients, total cholesterol (TC), low-density lipoprotein (LDL)-C, and ApoB levels were significantly higher than that of HD patients. HD patients with E3/4 genotype had elevated TC, LDL-C and ApoB levels compared with E3/3 genotype. TC and triglyceride levels were also higher in E3/4 genotype than that of E2/3 genotype. PD and HD patients showed a significantly increased PAI-1 levels compared with controls, whereas PAI-1 levels were highest in HD patients. There was no significant relation between ApoE genotypes and PAI-1 levels. CONCLUSIONS: The present study suggests that ApoE polymorphism significantly affects serum lipid profile in HD patients and epsilon4 allele carriers are more susceptible to have atherogenic lipid profile.     

Increased circulating levels of natriuretic peptides predict future cardiac event in patients with chronic hemodialysis

BACKGROUND/AIMS: Cardiovascular events are the major determinant of the prognosis in patients with chronic hemodialysis. The present study was designed to investigate whether increased plasma levels of atrial or brain natriuretic peptides (ANP or BNP) predict future cardiac events in such patients. METHODS: Fifty-three patients undergoing chronic hemodialysis without clinical symptoms suggestive of cardiac disorders were enrolled and their blood was sampled for ANP and BNP measurements. Electrocardiograms demonstrated left ventricular hypertrophy in 28 patients but no other abnormal findings. We followed them up for 11.3 +/- 0.2 months. The endpoint was cardiac events. RESULTS: Cardiac events occurred in 13 patients (CE group). Both ANP and BNP levels were higher in CE group than in patients without cardiac events (ANP: 118 +/- 21 vs. 56 +/- 5 pg/ml, BNP: 769 +/- 204 vs. 193 +/- 25 pg/ml, respectively). Receiver operating characteristics curve revealed that the cut-off levels of ANP and BNP were 58 and 390 pg/ml, respectively. Using the Kaplan-Meier method, the incidence of cardiac events was significantly greater in patients with higher levels of ANP (50.0 vs. 0.0%) or BNP (72.7 vs. 11.9%) than in those with lower levels of the peptides. CONCLUSIONS: Elevated levels of ANP or BNP indicate an increased risk of cardiac events and these peptides are clinically useful to predict cardiac events in patients with hemodialysis.