Hemodialysis patients with intradialytic rise in blood pressure display higher baseline aortic stiffness and negligible drop in augmentation index with dialysis.

BACKGROUND: In hemodialysis patients, the intradialytic rise in blood pressure (BP) is associated with increased mortality risk. However, the mechanisms of this adverse effect are not yet elucidated. This study examined whether intradialytic rise in BP is associated with increased arterial stiffness and wave reflections, which are powerful cardiovascular risk predictors in hemodialysis. METHODS: The pattern of intradialytic hemodynamic response was evaluated in 70 prevalent hemodialysis patients, by measuring seated brachial BP before and after the mid-week dialysis session. All patients had pre- and post-dialysis determination of aortic pulse wave velocity (PWV) and heart rate-adjusted augmentation index [AIx(75)], as measures of arterial stiffness and wave reflections, with the Sphygmocor device. RESULTS: Intradialytic rise in brachial systolic BP (SBP) was evident in 17 patients, whereas intradialytic change in SBP (ΔSBP) of -10 to 0 mmHg was observed in 23 and ΔSBP greater than -10 mmHg in 30 patients. Participants with intradialytic SBP rise had significantly higher pre-dialysis aortic PWV (10.4 ± 1.6 vs 8.3 ± 1.9 vs 9.4 ± 2.4 m/s, P < 0.01) and AIx(75) (28.1 ± 7.3 vs 21.7 ± 8.6 vs 25.8 ± 8.2%, P < 0.05) than those experiencing intradialytic ΔSBP of -10 to 0 and greater than -10 mmHg, respectively. Patients with rise in SBP during dialysis exhibited also lower intradialytic reduction in AIx(75) (-1.5 ± 4.9 vs -5.4 ± 5.9 vs -6.7 ± 5.3%, P < 0.001). CONCLUSIONS: This study shows that aortic stiffness and wave reflections are higher and not affected by dialysis procedure in patients with intradialytic SBP rise, suggesting that accelerated arteriosclerosis may be one possible explanation for the heightened cardiovascular risk associated with intradialytic hypertension.

Ambulatory recording of wave reflections and arterial stiffness during intra- and interdialytic periods in patients treated with dialysis.

BACKGROUND AND OBJECTIVES: Wave reflections and arterial stiffness are independent cardiovascular risk factors in ESRD. Previous studies in this population included only static recordings before and after dialysis. This study investigated the variation of these indices during intra- and interdialytic intervals and examined demographic, clinical, and hemodynamic variables related to arterial function in patients undergoing hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Between February 2013 and May 2014, a total of 153 patients receiving maintenance hemodialysis in five dialysis centers of northern Greece underwent ambulatory BP monitoring with the newly introduced Mobil-O-Graph device (IEM, Stolberg, Germany) over a midweek dialysis session and the subsequent interdialytic period. Mobil-O-Graph is an oscillometric device that records brachial BP and pulse waves and estimates, via generalized transfer function, aortic BP, augmentation index (AIx) as a measure of wave reflections, and pulse wave velocity (PWV) as an index of arterial stiffness. RESULTS: AIx was lower during dialysis than in the interdialytic period of dialysis-on day (Day 1) (mean±SD, 24.7%±9.7% versus 26.8%±9.4%; P<0.001). In contrast, PWV remained unchanged between these intervals (9.31±2.2 versus 9.29±2.3 m/sec; P=0.60). Both AIx and PWV increased during dialysis-off day (Day 2) versus the out-of-dialysis period of Day 1 (28.8%±9.8% versus 26.8%±9.4% [P<0.001] and 9.39±2.3 versus 9.29±2.3 m/sec [P<0.001]). Older age (odds ratio [OR], 1.09; 95% confidence interval [95% CI], 1.02 to 1.15), female sex (OR, 7.56; 95% CI, 1.64 to 34.81), diabetic status (OR, 8.84; 95% CI, 1.76 to 17.48), and higher mean BP (OR, 1.17; 95% CI, 1.09 to 1.27) were associated with higher odds of high AIx; higher heart rate was associated with lower odds (OR, 0.71; 95% CI, 0.63 to 0.80) of high AIx. Older age (OR, 2.04; 95% CI, 1.61 to 2.58) and higher mean BP (OR, 1.15; 95% CI, 1.05 to 1.27) were independent correlates of high PWV. CONCLUSIONS: This study showed a gradual interdialytic increase in AIx, whereas PWV was only slightly elevated during Day 2. Future studies are needed to elucidate the value of these ambulatory measures for cardiovascular risk prediction in ESRD.

Hemodiafiltration does not have additional benefits over hemodialysis on arterial stiffness, wave reflections and central aortic pressures.

BACKGROUND/AIMS: The hypothesis that dialytic modality affects arterial stiffness was never investigated. This study includes comparative evaluation of hemodiafiltration versus hemodialysis on arterial function during first and second weekly dialysis sessions. METHODS: 24 patients receiving hemodiafiltration and another 24 age- and sex-matched controls receiving hemodialysis were included. Patients were evaluated before and after first and second weekly dialysis sessions. Applanation tonometry of peripheral arteries was applied to determine aortic and brachial pulse wave velocity and heart rate-adjusted augmentation index (AIx(75)). RESULTS: Hemodiafiltration and hemodialysis reduced AIx(75), but not aortic and brachial pulse wave velocity. Intradialytic reductions in AIx(75) did not differ between hemodiafiltration and hemodialysis in first and mid-week dialysis. In multivariate linear regression, predictors of intradialytic reduction in AIx(75) were changes in body weight and central aortic systolic blood pressure, but not dialytic modality. CONCLUSION: This study showed that hemodiafiltration has similar effects with hemodialysis on wave reflections and stiffness.

Diverse effects of interdialytic intervals on central wave augmentation in haemodialysis patients.

BACKGROUND: Increased arterial stiffness is a common finding and independent predictor of mortality in end-stage renal disease (ESRD) patients. A long interdialytic interval was associated with increased risk of cardiovascular death in patients receiving conventional haemodialysis (HD). This is the first study to examine the effects of a long (3-day) versus short (2-day) interdialytic period on arterial elasticity in HD patients. METHODS: Seventy ESRD patients receiving standard HD three times per week were studied at the start and end of a 3-day and a 2-day interdialytic interval. At each time point, applanation tonometry of peripheral arteries was performed to assess arterial stiffness and wave reflection parameters. Aortic and brachial pulse wave velocities (PWV) were recorded as measures of arterial stiffness and augmentation index (AIx) as a measure of wave reflections. RESULTS: AIx, heart-rate-adjusted AIx and augmentation pressure were significantly increased during both interdialytic intervals, whereas aortic and brachial PWVs remained unchanged. The interdialytic increases in all the three AIx parameters were significantly higher during the 3-day interval in comparison to the 2-day interval (P < 0.001 for all comparisons). In contrast, no significant differences in interdialytic changes of aortic (P = 0.355) and brachial (P = 0.319) PWVs were noted between the two intervals. Mixed linear model analysis revealed that central aortic systolic blood pressure (SBP) and body weight, but not aortic or brachial PWV, were independent determinants of the change in heart-rate-adjusted AIx throughout the study. CONCLUSIONS: AIx is increased between HD sessions, whereas arterial elasticity is not. This interdialytic increase in central wave augmentation is more pronounced during the 3-day interval, suggesting a mechanism possibly involved in the elevated cardiovascular risk of HD patients at this time point.

Omega-3 fatty acids supplementation does not affect serum lipids in chronic hemodialysis patients.

OBJECTIVE: The aim of this study was to test the hypothesis that omega-3 fatty acids have an effect on serum lipids and inflammation markers in chronic hemodialysis (HD) patients. DESIGN: The study followed a single-blind, randomized, crossover design. SETTING: The study was conducted at the Hemodialysis Unit of the Laikon General Hospital in Athens, Greece. PATIENTS: A total of 25 chronic HD patients were included in the study (16 men, 9 women, age: 51 ± 15 years). INTERVENTION: Patients were randomly assigned to one of the following 2 intervention groups: omega-3 fatty acids plus α-tocopherol (920 mg eicosapentaenoic Acid (EPA), 760 mg docosahexaenoic acid (DHA), 8 mg α-tocopherol in total per day) or α-tocopherol supplement (100 mg/week resulting in 14.2 mg/day) alone for 4 weeks. After a washout period of 4 weeks, the 2 groups were crossed. MAIN OUTCOME MEASURES: Medical history data were collected and anthropometric and nutritional intake evaluation was performed at the beginning and at the end of both interventions. Hematological and biochemical parameters as well as C-reactive protein levels were measured. RESULTS: No statistically significant results were recorded in the lipidemic profiles of the participants between baseline and the 2 interventions. C-reactive protein levels also did not change significantly between the 2 interventions (5.54 ± 3.33 to 6.70 ± 5.01 mg/L [P = .19] with vitamin E vs. 7.13 ± 5.04 to 6.87 ± 5.24 [P = .78] with omega-3, P overall = .53). CONCLUSION: The results of this study do not provide support for the positive effects of omega-3 fatty acid supplementation in HD patients.

Pharmacokinetics of moxifloxacin in patients undergoing continuous ambulatory peritoneal dialysis.

OBJECTIVE: To investigate the effect of continuous ambulatory peritoneal dialysis (CAPD) on plasma and peritoneal fluid concentration and pharmacokinetics of moxifloxacin after administration of one 400 mg dose orally to end-stage renal failure patients undergoing CAPD. PATIENTS AND METHODS: Blood and peritoneal samples were collected from 8 patients at standard time intervals and concentrations of moxifloxacin were estimated by HPLC analysis with fluorometric and ultraviolet detection. Pharmacokinetic parameters were estimated using standard noncompartmental methods. RESULTS: Median maximum plasma moxifloxacin concentration was 5.86 mg/L at a median time of 1.25 hours. In serum, median area under the concentration-time curve (AUC(0-->inf)) was 157.95 +/- 100.34 mg.hour/L, median t(1/2) 25.00 hours, median clearance 2.54 L/hour, and median distribution volume 94.90 L. Median peritoneal fluid-to-plasma ratio of moxifloxacin ranged between 0.84 and 1.00, denoting adequate penetration and lack of considerable moxifloxacin removal during CAPD. Maximum moxifloxacin concentration/minimum inhibitory concentration (MIC) and AUC(0-->24)/MIC ratios were above the cutoff points that indicate clinical success. CONCLUSION: A single 400 mg oral dose of moxifloxacin is safe, presents rapid peritoneal fluid penetration, has similar plasma and peritoneal fluid pharmacokinetics, and should therefore be efficacious in the treatment of CAPD-induced peritonitis.

Dialysate magnesium level and blood pressure.

BACKGROUND: We investigated the way dialysate magnesium (dMg) concentrations could affect blood pressure (BP) during hemodialysis (HD). METHODS: Eight HD patients underwent four midweek HD treatments consecutively, using, during each four-hour HD session, one of the following four dialysate formulations, in randomized order, which differed only with regard to dMg and dialysate calcium (dCa) concentrations (in mmol/L): 0.75 dMg, 1.75 dCa (group I); 0.25 dMg, 1.75 dCa (group II); 0.75 dMg, 1.25 dCa (group III); 0.25 dMg, 1.25 dCa (group IV). Before HD and at four 60-minute intervals during the HD sessions, BP and noninvasive measurements of cardiac index (CI) were obtained. Additionally, 14 HD patients were treated for four weeks with 0.5 mmol/L dMg, followed by four weeks with 0.25 mmol/L dMg, and another four weeks with 0.75 mmol/L dMg, in random order. In all treatments dCa was 1.25 mmol/L. BP and symptoms were recorded during each HD session. RESULTS: Mean arterial pressure (MAP) decreased to a significantly (P < 0.05) greater extent in group IV compared to the other groups. This substantial drop in MAP by 15.2% in group IV, paralleled by a 12.1% and 17% drop in CI and stroke index, respectively, was not seen in group II, despite comparable reductions in intradialytic serum Mg (sMg) of about 35% in both groups. In groups I and III, the increase in sMg by 2% did not compromise BP via vasodilatation. In the second study, treatment with 0.75 mmol/L dMg was superior to the other two treatments regarding intradialytic morbidity (P < 0.001) and BP stability (P < 0.05). CONCLUSION: We (1) identified a dialysis solution containing 0.25 mmol/L Mg and 1.25 mmol/L Ca as a major cause of intradialytic hypotension (IDH) due to an impairment of myocardial contractility, and (2) showed that increasing dMg level to 0.75 mmol/L could prevent IDH frequently seen with the use of 1.25 mmol/L dCa. Thus, manipulating dMg levels independently or in concert with dCa levels might have important implications with regard to dialysis tolerance.

Elevated leptin fragments in renal failure correlate with BMI and haematopoiesis and are normalized by haemodialysis.

OBJECTIVE: Leptin is an adipocyte hormone important in appetite, energy homeostasis, neuroendocrine and haematopoietic function. Patients with renal failure often have elevated total and free leptin levels. Biologically active leptin fragments (leptin(22-56) and leptin(57-92)) have been identified, but whether these fragments are affected by renal failure and/or haemodialysis (HD) is not known. RESEARCH METHODS: Leptin, leptin(22-56) and leptin(57-92) levels were measured in 28 HD patients [14 men, 14 women, age 45.5 +/- 16.4 years, body mass index (BMI) 23.8 +/- 3.6 kg/m2] and 25 healthy controls with similar age and BMI. In 18 HD patients, leptin and fragment levels were measured before and after 2 consecutive dialysis treatments and on the intermediate, dialysis-free day. RESULTS: Baseline leptin levels were higher in HD patients vs. controls (69.3 +/- 62.2 ng/ml vs. 30.4 +/- 32.7, P < 0.02) as were leptin(22-56) (7.14 +/- 7.04 ng/ml vs. 1.86 +/- 1.84, P < 0.02) and leptin(57-92) (5.94 +/- 6.08 ng/ml vs. 1.58 +/- 1.98, P < 0.02). Baseline leptin and fragment levels correlated significantly and independently with BMI in HD patients (r = 0.70, r = 0.59, r = 0.72, respectively, P < 0.001). After each HD session, leptin levels were reduced to levels not different from controls, but increased on the intermediate, dialysis-free day. Similar to and independently from total leptin, both leptin fragments were reduced after the first HD session to levels not different from controls. The reduction in leptin levels was higher with synthetic vs. cellulosic membrane types (37.7 +/- 23.5%vs. 18.1 +/- 21.8%, P < 0.03). Leptin correlated weakly with the erythropoietin to haematocrit ratio (T = -0.20, P = 0.14), while leptin(22-56) had a significant negative correlation with this index (T = -0.42, P < 0.01), suggesting that this fragment may favour haematopoiesis. DISCUSSION: Leptin fragments are detected in human serum, and both leptin and leptin fragments correlate with BMI, are significantly elevated in HD patients compared to controls, and are significantly decreased by haemodialysis. The elevated leptin fragments may have important physiological significance for the anorexia, hypogonadism, and anaemia commonly seen in HD patients, but this remains to be conclusively shown by interventional trials.

Pharmacokinetics of teicoplanin in patients undergoing continuous ambulatory peritoneal dialysis.

OBJECTIVE: To achieve concentrations of teicoplanin in serum and dialysate within the therapeutic range in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Pharmacokinetic study. SETTING: A tertiary-care hospital. PATIENTS: Eight hospitalized anuric patients undergoing CAPD. INTERVENTIONS: One single dose of 10 mg/kg teicoplanin was administered intravenously, and blood and dialysate were sampled at regular time intervals for 48 hours post drug infusion. Concentrations of teicoplanin were determined by microbiological assay. RESULTS: Teicoplanin serum levels above 10 microg/mL, the level desired to treat systemic infections, were detected for 24 hours after administration. All dialysate concentrations were very low. Teicoplanin presented two phases of elimination: an early first phase and a late second phase. Mean maximum serum concentration was 75.56 microg/mL, mean half-life (t 1/2) of the early elimination was 3.34 hours, mean t 1/2 of the late elimination was 61.68 hours, mean area under the serum-concentration-time curve was 1491.92 mg x hr/L, mean clearance rate was 10.68 mL/ minute, mean apparent volume of distribution was 0.80 L/kg, and mean volume of distribution at steady state was 0.22 L/kg. Mean dialysate excretion was 3.16% and mean peritoneal clearance rate was 0.023 mL/minute. CONCLUSIONS: Based on the time period with the achieved serum levels and on the prolonged t 1/2, it is proposed that teicoplanin might be administered at 10 mg/kg every 24 hours for the therapy of systemic infections in patients undergoing CAPD. However, its intravenous administration should be avoided in the treatment of peritonitis, because the achieved dialysate concentrations were very low.

Pharmacokinetics of teicoplanin in patients undergoing chronic haemodialysis.

In order to define a dose regimen of teicoplanin for patients undergoing chronic haemodialysis so that they achieved trough drug serum levels above 10 mg/l, two single doses of 5 and 10 mg/kg were administered intravenously in seven anuric patients immediately after the end of haemodialysis. Concentrations of teicoplanin were determined by a microbiological assay in samples collected from peripheral veins via the arterial and the venous lines of the fistulae and from the dialysate during haemodialysis. The administration of a 5 and 10 mg/kg dose gave mean C(max) of 62.80 and 122.43 mg/l, mean AUC of 526.43 and 1103.98 mg h/l, mean half life (t(1/2)) of 109.09 and 107.06 h, mean clearance rates of 12.85 and 12.44 ml/min, mean apparent volumes of distribution of 1.68 and 1.68 l/kg and mean volumes of distribution at steady state of 0.31 and 0.28 l/kg, respectively. Trough serum levels above 10 mg/l were found for 24 h after the administration of the 5 mg/kg dose and for 48 h after the administration of the 10 mg/kg dose. Teicoplanin was not detected in the dialysate. Its concentrations in both the arterial and the venous lines of the fistulae were similar. Based on the time period after the administration of teicoplanin where the desired trough serum levels were found and on the observed t(1/2), it is proposed that teicoplanin should be administered at a dose of 10 mg/kg at 48-72 h intervals, in patients undergoing chronic haemodialysis for the therapy of infections caused by Gram-positive cocci.