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

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

Use of myocardial tissue Doppler imaging for intraoperative monitoring of left ventricular function

Background. Detection of myocardial ischaemia during surgeryis usually by assessment of regional wall motion using two-dimensionaltransoesophageal echocardiography (TOE). Tissue Doppler imaging(TDI) may assist this assessment and improve its accuracy. Methods. We measured peak myocardial velocities in the anteriormid-wall of the left ventricle by TOE and pulsed-wave TDI inaddition to transmitral flow velocity, two-dimensional echocardiographyand cardiovascular variables. We studied 42 patients beforeand after coronary bypass surgery with left internal mammaryartery grafts. Results. Peak systolic and early and late diastolic velocitymeasurements of the anterior mid-wall were obtained in all patients.Variation between and within observers was small (<6%). Peaksystolic thickening velocity correlated with visual assessmentof anterior wall motion score, fractional area change of theleft ventricle and left ventricular systolic wall stress. Becauseof the wide overlap of systolic velocity between the segmentswith normal and abnormal wall motion, it was not possible toseparate normal from abnormal segments on the basis of TDI-derivedvelocity alone. The diastolic velocity in the anterior wallreflected the transmitral filling pattern. After surgery, thepeak systolic and late diastolic anterior wall velocities increased(from 4.2 (95% confidence interval 4.0, 4.7) to 5.7 (4.8, 6.3)cm s^–1 and from 3.5 (3.2, 3.9) to 6.0 (5.1, 6.9)cm s^–1 respectively), while the ratio of early tolate diastolic velocity decreased from 1.5 (1.2, 1.7) to 1.0(0.8, 1.2). TDI changes characteristic of new myocardial ischaemiawere not seen in any patient. Conclusion. Intraoperative measurement of TDI in the anteriorwall of the left ventricle is feasible and provides additionalquantitative information on both regional and global systolicand diastolic function. We found changes in myocardial velocitiesindicating improvement in the systolic and impairment in thediastolic function of the anterior wall of the left ventricleimmediately after mammary artery grafting. Br J Anaesth 2003; 91: 473–80     

Acute effects of haemodialysis on endothelial function and large artery elasticity.

BACKGROUND: Disturbances of functional properties of large arteries contribute to increased cardiovascular morbidity and mortality in patients with end-stage renal disease. However, it is not clear whether haemodialysis per se acutely affects mechanical vessel wall properties or endothelial function. METHODS: Twenty-five chronic haemodialysis patients (mean+/-standard error of the mean (SEM): age 52+/-5 years; time on dialysis 63+/-7 months; blood pressure 132+/-4/72+/-2 mmHg) were studied before and immediately after a haemodialysis (HD) session using a polysulphone dialyser (ultrafiltration 1460+/-54 ml), as well as on the following day. Blood pressure was measured with an automatic sphygmomanometer and applanation tonometry. End-diastolic diameter and distension of the brachial and carotid arteries were measured by Doppler frequency analysis of vessel wall movements in M-mode using a multigate pulsed Doppler system and aortic pulse wave velocity (PWV) by an automatic device (Complior). Endothelial function was determined as brachial artery flow-mediated dilation (FMD) and compared with endothelium-independent nitroglycerine-induced dilation (NMD). RESULTS: FMD was 7.9+/-1.8% in patients before HD and did not change significantly after HD or in the dialysis-free intervall (6.7+/-2.1 and 7.1+/-2.0%, respectively; NS). The same was true for NMD and PWV (12.6+/-0.8 m/s before HD, 12.8+/-0.8 m/s after HD, and 11.9+/-0.7 m/s on the HD-free day). Carotid distensibility coefficients decreased significantly during HD (from 18.1+/-1.9 x 10(-3)/kPa to 16.7+/-2.2 x 10(-3)/kPa, P<0.05) and increased again on the HD-free day (19.8+/-2.4 x 10(-3)/kPa). However, when corrected for blood pressure by tonometry, isobaric carotid distensibility did not change significantly. Brachial artery distensibility also did not show significant acute changes. CONCLUSIONS: Haemodialysis per se did not have a significant effect on endothelial function or large artery mechanical vessel wall properties in patients on maintenance dialysis therapy.     

Assessment of left ventricular function by tissue Doppler echocardiography in pediatric chronic kidney disease

Abstract

Background: Cardiovascular (CV) disease remains the most common cause of mortality in chronic kidney disease (CKD). Methods: In this cross-sectional study, 43 pediatric patients with CKD were divided into two groups according to their estimated glomerular filtration rate (eGFR): groups 1 and 2 (eGR; 29–75 and 15–29?mL/min/1.73?m², respectively). M – mode, conventional pulsed wave Doppler (cPWD) echocardiography and tissue Doppler imaging (TDI) were performed in all patients and 16 healthy controls. Maximal early (E wave) and late (A wave) diastolic flow velocities were assessed by cPWD. Using TDI, the early (E′) and late (A′) diastolic filling velocities were recorded. Early and late diastoles were evaluated using E′ values and E/E′ ratios, respectively. Results: Left ventricular hypertrophy (LVH) was determined in 19/43 (44.2%) patients. The E/E′ ratio was significantly higher in group 2 than in group 1 and controls. E/E′ was found to be positively correlated with left ventricular mass (LVM) index, and negatively with hemoglobin (Hb) levels. Low Hb levels were only independent predictor of E/E′ (p?=?0.001, β: ?0.470, 95% CI: ?0.764; ?0.196). E′ ratio was significantly lower in both patient groups compared to the controls. Conclusions: LVH and diastolic dysfunction are already present in early stages of CKD. Treatment of risk factors, such as anemia, is important to improve the clinical outcome.     

The assessment of fluid status in haemodialysis patients: usefulness of the Doppler echocardiographic parameters.

BACKGROUND: In end-stage renal disease (ESRD) patients undergoing regular haemodialysis (HD), the maintenance of fluid status within an optimal range is critical. We therefore examined the role of Doppler echocardiographic parameters in the assessment of fluid status in these patients. METHODS: Three study groups were enrolled: 40 healthy volunteers (NTNR), 40 HD patients who were normotensive without receiving antihypertensive agents (NTHD) and 38 HD patients who had remained hypertensive (HTHD) despite antihypertensive treatment. Measurements of Doppler echocardiographic parameters from pulmonary vein (PV) and mitral inflow (Mi) were performed on a non-dialysis day. Extracellular water as a percentage of body weight (ECW%) and pre-dialysis mean blood pressure (BDMBP) were references for fluid status. The best Doppler parameter for fluid status assessment identified from the study groups was then tested in another validation groups (38 NTHD and 38 HTHD). RESULTS: Among all of the PV and Mi parameters, the S/D ratio (peak systolic velocity divided by peak diastolic velocity) was correlated with fluid status parameters best (with ECW%, r = -0.49, P<0.001; with BDMBP, r = -0.51, P<0.001). The correlations were independent of age, sex and Mi parameters. The receiver operating characteristics curve analysis demonstrated that an S/D ratio >1.33 had a sensitivity of 90% and a specificity of 77% in identifying NTHD patients. When the same criterion was applied to the validation groups, the positive predictive value was 64% and the negative predictive value was 86%. CONCLUSION: The Doppler-derived S/D ratio is a potentially useful marker for the assessment of fluid status in HD patients.     

Left ventricular function in patients with chronic kidney disease evaluated by colour tissue Doppler velocity imaging.

BACKGROUND: Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD) patients. Tissue Doppler velocity imaging (TVI) is a new objective method that accurately quantifies myocardial tissue velocities, deformation, time intervals and left ventricular (LV) filling pressure. In this study, TVI was compared with conventional echocardiography for the assessment of left ventricular (LV) function in pre-dialysis patients with different stages of CKD. The results obtained by TVI were used to analyse possible relationships between LV function and clinical factors such as hyperparathyroidism and hypertension that could influence LV function. METHODS: Conventional echocardiography and TVI images were recorded in 40 patients (36 men and 4 women, mean age 60+/-14 years, range 28-80 years) and in 27 healthy controls (21 men and 6 women, mean age 58+/-17 years, range 28-82 years). Twenty-two patients had mild/moderate CKD (CCr>29 ml/min; Group 1) and 18 patients had severe CKD (CCr相似文献   

Systolic long axis function of the left ventricle. Global and regional information

Objective—To compare global systolic measurements of mitral annular motion by M‐mode and tissue velocity time integral, and annular velocity by pulsed and colour Doppler for precision and bias. Secondly, to compare the ability of annular motion to identify regional dysfunction with segmental analysis by strain rate imaging.

Design—Nineteen normal subjects and 19 patients with myocardial infarction were studied with echocardiography.

Results—There were significant correlations between ejection fraction (EF) and annular motion/velocity by all methods, ranging from 60 to 80%. Measurements had 95% limits of agreement intervals between 7.7 and 15.6?mm for annulus excursion and 8.8?cm/s for annulus velocities with biases between methods of 0.7–1.9?mm and 2.6?cm/s. Annular motion and velocity were reduced in the patients compared with the control group, but were depressed at all points so the infarcted region could not be identified. Only segmental analysis could identify the region of dyssynergy.

Conclusion—Annular motion and velocity measure global function, but have high variability and measurements are method dependent. Only segmental analysis can identify regional dyssynergy. This is possible with strain rate imaging, but the precision is still too low for clinical use.     

Clinical and Doppler ultrasonography data of a polyurethane vascular access graft for haemodialysis: a prospective study.

BACKGROUND: Absence of a permanent vascular access in most patients starting haemodialysis remains a cause of high morbidity and costs. This study obtained new clinical and colour Doppler ultrasound (CDU) data of a polyurethane vascular access graft (PVAG) proposing early post-operative cannulation. METHODS: Baseline characteristics were determined in 15 patients and the PVAGs were evaluated prospectively including first cannulation, patency and complications. CDU was used post-operatively and after 1 year for assessing graft morphology and access blood flow. RESULTS: PVAGs were cannulated at a median of 4 days post-operatively. The 1-year primary patency of the PVAG was 66.7%. During the 15 months observation three grafts thrombosed, one was replaced because of infection and one because of ischaemia. CDU measurements at the feeding brachial artery revealed a mean initial access volume flow of 773+/-89 ml/min, being significantly higher in patients without thrombosis compared to patients with thrombotic events (930+/-90 vs 375+/-143 ml/min, P<0.05). The initial inability to directly monitor PVAGs by CDU changed at sites of frequent centesis, where Doppler signals and luminal morphology could be evaluated in the follow up examination. CONCLUSIONS: The PVAG offers early access for urgent haemodialysis. CDU for access volume flow measurement at the feeding brachial artery contributes to predict access thrombosis. Direct non-invasive graft imaging is limited and the ultrasonographical changes in the polyurethane material enabling graft monitoring after repeated cannulation might indicate an injury of the graft with increased risk for access failure.     

Different effects of enoxaparin and unfractionated heparin on extrinsic blood coagulation during haemodialysis: a prospective study.

BACKGROUND: Heparin inhibits prothrombotic tissue factor (TF) and releases its inhibitor, tissue factor pathway inhibitor (TFPI), from the endothelium, but repeated administration of heparin depletes vascular stores of TFPI. We studied the anticoagulant effects of unfractionated heparin (UFH) vs low-molecular-weight enoxaparin-used for thrice-weekly maintenance haemodialysis (HD)-on plasma levels of total TF and TFPI and on those of an activated coagulation marker prothrombin fragment 1+2 (PF 1+2). METHODS: Twenty-five patients dialysed using a single injection of enoxaparin (at a mean dose of 0.68 mg/kg) were randomly assigned to either receive UFH administered as a mean bolus of 42.1 IU/kg and continuous infusion of 57.8 IU/kg (n=12) or to be maintained on enoxaparin (n=13), and were followed prospectively for 12 weeks. Plasma immunoreactive TF, TFPI and PF 1+2 were measured at the start and after 10 and 180 min of HD, and compared with values in 15 healthy controls. RESULTS: Pre-dialysis TF, TFPI and PF 1+2 were higher than normal (all P<0.0001). TF and PF 1+2 did not change, while TFPI levels, compared with baseline, increased at each interval in enoxaparin-anticoagulated HD patients (all P<0.0001). TFPI increments correlated inversely with pre-dialysis TFPI (both P<0.0007). In patients switched to UFH, TF levels remained unchanged compared with pre-randomization values, TFPI increased at each interval of HD sessions (all P<0.035) and PF 1+2 increased pre-dialysis (P=0.015). The over-dialysis effects of UFH resembled those of enoxaparin. In contrast, baseline TFPI and its 10-min rise correlated inversely with the UFH loading dose (both P<0.040). Pre-dialysis PF 1+2 was inversely associated with TFPI increments (both P<0.034), and directly with pre-dialysis TFPI (P=0.018) and the UFH loading dose (P=0.045). CONCLUSIONS: Depletion of heparin-releasable stores of TFPI is an untoward effect of repeated anticoagulation during maintenance HD therapy. The traditional UFH regimen is more prothrombotic than single enoxaparin injections, with high loading doses of UFH being involved in TFPI exhaustion and subsequent hypercoagulability.     

The effects of maintenance recombinant human erythropoietin therapy on ambulatory blood pressure recordings: conventional, Doppler, and tissue Doppler echocardiographic parameters

Abstract: Cardiovascular disease is the major cause of mortality in maintenance hemodialysis patients. Left ventricular dysfunction is present in approximately 80% of these patients and is highly predictive of future ischemic heart disease, cardiac failure, and death. Anemia has been identified as one of several risk factors responsible for cardiac complications. The treatment of renal anemia with recombinant human erythropoietin (rHuEpo) and consequent improvement of cardiac performance may reverse pathological changes in left ventricular geometry. In this study, the acute and chronic effects of rHuEpo administration on 24‐hour ambulatory blood pressure recordings and echocardiographic parameters in 30 rHuEpo‐naïve maintenance hemodialysis patients were examined. Twenty‐four‐hour ambulatory blood pressure monitoring was performed prior to and after 1 week and 6 months of rHuEpo administration. The patients underwent echocardiographic examination prior to and after 6 months of rHuEpo administration. One week treatment with rHuEpo did not cause any significant change in 24‐hour ambulatory blood pressure recordings. After 6 months of therapy, serum hemoglobin levels increased from 8.8 ± 0.66 g/dL to 10.8 ± 0.70 g/dL (P < 0.05). Echocardiographic examination revealed elevation in ejection fraction (62.26 ± 6.84% vs. 69.90 ± 8.98%, P < 0.05) with reductions in fractional shortening (36.70 ± 4.96% vs. 35.96 ± 6.32%, P < 0.05), interventricular septum thickness (1.21 ± 0.16 vs. 1.00 ± 0.16 cm, P < 0.05), and left ventricular mass index (148.2 ± 46.5 g/m² vs. 93.6 ± 17.2 g/m², P < 0.05). Doppler echocardiography and tissue Doppler imaging provided additional information in comparison with conventional echocardiography. Before treatment, mitral flow E wave (E, 0.64 ± 0.27 vs. 0.82 ± 0.17 cm/s), mitral flow A wave (A, 0.80 ± 0.21 vs. 0.70 ± 0.21 cm/s), early diastolic velocity of lateral wall (Lateral E′, 11.2 ± 2.8 vs. 12.4 ± 2.3 cm/s), late diastolic velocity of lateral wall (Lateral A′, 6.7 ± 2.5 vs. 7.8 ± 2.1 cm/s), early diastolic velocity of septal wall (Septal E′, 9.7 ± 2.9 vs. 11.3 ± 1.1 cm/s), and late diastolic velocity of septal wall (Septal A′, 6.4 ± 2.1 vs. 7.8 ± 2.0 cm/s) were significantly lower in patients than in the controls. Patients and controls have similar deceleration time of mitral flow E wave (E Dec, 186 ± 57.8 vs. 192 ± 62.4 ms), isovolumic left ventricular relaxation time (IVRT, 111.9 ± 30.7 vs. 91.1 ± 32 ms), systolic velocity of lateral wall (Lateral S′, 7.8 ± 2.3 vs. 8.1 ± 2.0 cm/s), and systolic velocity of septal wall (Septal S′, 7.5 ± 1.9 vs. 7.7 ± 1.4 cm/s) values. Therapy with rHuEpo did not cause significant changes in E (0.64 ± 0.27 vs. 0.76 ± 0.29 cm/s), A (0.80 ± 0.21 vs. 0.79 ± 0.23 cm/s), E Dec (186 ± 57.8 vs. 165.8 ± 60.1 ms), IVRT (111.9 ± 30.7 vs. 101.6 ± 36.2 ms), Lateral E′ (11.2 ± 2.8 vs. 11.5 ± 4.4 cm/s), Lateral A′ (6.7 ± 2.5 vs. 7.4 ± 2.1 cm/s), Lateral S′ (7.8 ± 2.3 vs. 8.1 ± 2.0 cm/s), Septal E′ (9.7 ± 2.9 vs. 10.0 ± 1.1 cm/s), Septal A′ (6.4 ± 2.1 vs. 6.6 ± 2.0 cm/s), and Septal S′ (7.5 ± 1.9 vs. 7.9 ± 1.4 cm/s) indicating persistence of diastolic dysfunction. In 6 months time, 24‐hour ambulatory blood pressure recordings, however, tended to be higher (systolic: 125.16 ± 21.02 mm Hg vs. 134.36 ± 23.98 mm Hg; diastolic: 77.40 ± 14.47 mm Hg vs. 83.26 ± 14.89 mm Hg, P < 0.05). Correction of anemia with rHuEpo results in the elevation of blood pressure and reduction in left ventricular mass index. Myocardial contraction and relaxation velocities did not improve following regression of left ventricular hypertrophy, suggesting the persistance of diastolic dysfunction. Doppler echocardiography with tissue Doppler imaging reflects the real situation of diastolic function in patients on maintenance hemodialysis.     

Treatment with different doses of folic acid in haemodialysis patients: effects on folate distribution and aminothiol concentrations.

BACKGROUND: Hyperhomocysteinaemia is highly prevalent among haemodialysis patients and may contribute to their increased cardiovascular risk. Treatment with pharmacological doses of folic acid lowers the plasma homocysteine concentration in these patients. The purpose of the present study was to expand the knowledge about such treatment by testing the effects of stepwise increases in the dose of folic acid on the concentrations of plasma and red blood cell folate as well as the total plasma concentrations of homocysteine (tHcy), cysteine (tCys), and glutathione (tGSH) in patients on chronic hemodialysis. METHODS: Fourteen stable haemodialysis patients completed the study which consisted of four consecutive periods, each of 6 weeks duration: (i) no treatment with folic acid (control period); (ii) 5 mg of folic acid three times per week (15 mg/week); (iii) 5 mg of folic acid daily (35 mg/week); (iv) 10 mg of folic acid daily (70 mg/week). RESULTS: Neither plasma or red cell folate nor plasma aminothiol concentrations changed significantly during the control period. The mean red cell folate concentration doubled during the administration of folic acid at the dose of 15 mg/week but at higher doses the further rise was only marginal. The mean folate concentration in plasma increased steeply especially at the higher doses of folic acid. During treatment with 15 mg/week of folic acid, tHcy fell by a mean of 36%, tGSH increased by a mean of 34%, but tCys was unaffected. Increases in the dose of folic acid did not augment these responses. CONCLUSIONS: The maximal effect on tHcy seemed to be obtained already at the lowest given dose of folic acid (15 mg/week). At that dose, the red blood cells approached folate saturation, which may reflect the situation in other cells that participate in homocysteine metabolism and explain why further increases in the dose of folic acid are not effective from a tHcy-lowering point of view.     

Hypochlorous acid and low serum paraoxonase activity in haemodialysis patients: an in vitro study.

BACKGROUND: Serum paraoxonase 1 (PON1) is an oxidant-sensitive enzyme associated with high-density lipoprotein (HDL) that inhibits the atherogenic oxidation of low-density lipoprotein (LDL). In haemodialysis patients, production of reactive oxygen species, such as hypochlorous acid (HOCl) and hydrogen peroxide, is increased and serum PON1 arylesterase is abnormally low. We have examined the effect of HOCl and the uraemic milieu on serum PON1 arylesterase activity and the ability of HDL to inhibit LDL oxidation in vitro. METHODS: Serum was incubated with HOCl, hydrogen peroxide and products of HOCl reaction with excess cysteine, lysine and taurine and then serum PON1 arylesterase and serum protein tryptophan fluorescence were measured. The ability of plasma HDL fractions isolated by a dextran-sulphate method, to protect LDL from mild oxidation in air, was determined by a fluorimetric method using oxidation of 2,7-dichlorofluorescein (DCFH). RESULTS: Incubation of healthy serum with HOCl in the range 6.5-32.9 mmol/l resulted in a linear decrease in serum PON1 arylesterase activity to 40% of that without HOCl and a parallel decrease in protein tryptophan fluorescence. The HOCl-induced decrease in serum PON1 activity was completely removed by reaction of HOCl with a 2.7-fold excess of alpha-amino acids but not taurine. In serum incubated for 1 week, the decrease in serum PON1 activity was significantly (P = 0.04) less while the increase in protein fluorescent advanced glycation end-products was significantly larger (P = 0.01) in haemodialysis patients compared with healthy subjects. The mean decrease in mild oxidation of LDL was not significantly different on addition of HDL-rich fractions from haemodialysis patients (100 +/- 6%, n = 7) and healthy subjects (95 +/- 6%, n = 7) or on addition of the HDL-rich fraction from plasma treated with 0.95 mmol/l HOCl (95%) and control HDL (96%). The fraction rich in HDL and other high molecular weight compounds from plasma that had been incubated with increasing HOCl concentrations up to 1.9 mmol/l significantly (P = 0.001) increased (471%) the oxidation of DCFH. CONCLUSIONS: These results suggest that high concentrations of HOCl that severely oxidize serum proteins and tryptophan residues in the active site of PON1 are required to decrease PON1 arylesterase activity in serum. In haemodialysis patients, overproduction of HOCl that leads to high concentrations of severely oxidized proteins and increased oxidants in plasma might also contribute to low serum PON1 arylesterase activity, but does not appear to impair the ability of an HDL molecule to protect LDL from mild oxidation.     

Elimination of intravenously administered ibandronate in patients on haemodialysis: a monocentre open study.

BACKGROUND: Ibandronate is an inhibitor of osteoclast-mediated bone resorption. This therapeutic effect is utilized in the treatment of osteoporosis and metastatic bone disease. The effect of ibandronate in patients on haemodialysis with renal osteopathy has not been studied since the pharmacokinetics of ibandronate under haemodialysis are unknown. METHODS: We analysed the removal of ibandronate from the plasma by haemodialysis in 12 chronic haemodialysis patients suffering from end-stage renal disease (ESRD). After intravenous administration of 1 mg ibandronate, the plasma concentration of ibandronate was determined in plasma samples drawn before entering (inflow) and after passing through (outflow) the haemodialyser, and in the dialysate at 1, 2, 3 and 4 h during the first haemodialysis session, and after 1 and 4 h during the second and third dialysis sessions. RESULTS: The back-extrapolated initial ibandronate plasma level was 38.9+/-15.9 ng/ml; this decreased during first haemodialysis (after 4 h) to 4.9+/-0.9 ng/ml and after two subsequent haemodialysis treatments to 0.38+/-0.16 ng/ml. Ibandronate concentration was reduced by 47% with every passage through the dialyser. The total decrease of ibandronate plasma concentration during the first 4 h of haemodialysis was 78% of plasma peak levels. The ibandronate dialysis plasma clearance was determined at 92+/-19 ml/min. The total amount excreted at the first dialysis using the recovery rate measure was 364+/-98 microg and using the mean difference in inflow/outflow (arteriovenous) concentration (A-V difference method) it was 371+/-132 microg. About 36% of the total amount of ibandronate administered (1 mg) was removed by the first dialysis treatment. CONCLUSION: Ibandronate was efficiently removed by haemodialysis. After three haemodialysis sessions the ibandronate plasma levels were close to quantification limit. One monthly dose of 1 mg ibandronate would not result in elevated plasma levels in patients with ESRD on haemodialysis treatment three times a week. In haemodialysis patients, ibandronate should be administered after the haemodialysis session.     

Association between high ultrafiltration rates and mortality in uraemic patients on regular haemodialysis. A 5-year prospective observational multicentre study.

BACKGROUND: High ultrafiltration rate on haemodialysis (HD) stresses the cardiovascular system and could have a negative effect on survival. METHODS: The effect of ultrafiltration rate (UFR; ml/h/kg BW) on mortality was prospectively evaluated in a cohort of 287 prevalent uraemic patients in regular HD from 1 January 2000 to 31 December 2005. Patients: 165 men and 122 women, age 66 +/- 13 years, on regular HD for at least 6 months, median: 48 months (range 6-372 months). Mean UFR was 12.7 +/- 3.5 ml/h/kg BW, Kt/V: 1.27 +/- 0.13, body weight (BW): 62 +/- 13 kg, PCRn: 1.11 +/- 0.20 g/kg/day, duration of dialysis: median 240 min (range 180-300 min), mean arterial blood pressure (MAP) 99 +/- 9 mm/Hg. One hundred and forty nine patients (52%) died, mainly for cardiovascular reasons (69%). Multivariate Cox regression analysis was utilized to evaluate the effect on mortality of UFR, age, sex, dialytic vintage, cardiovascular disease (CVD), diabetes, dialysis modality, duration of HD, BW, interdialytic weight gain (IWG), body mass index (BMI), MAP, pulse pressure (PP), Kt/V, PCRn. RESULTS: Age (HR 1.06; CI 1.04-1.08; P < 0.0001), PCRn (HR 0.17, CI 0.07-0.43; P < 0.0001), diabetes (HR 1.81, CI 1.24-2.47; P = 0.007), CVD (HR 1.86; CI 1.32-2.62; P = 0.007) and UFR (HR 1.22; CI 1.16-1.28; P < 0.0001) were identified as factors independently correlated to survival. We estimated the discrimination potential of UFR, evaluated at baseline, in predicting death at 5 years, calculating the relative receiver operating characteristic (ROC) curves and the cut-off that minimizes the absolute difference between sensitivity and specificity. CONCLUSIONS: High UFRs are independently associated with increased mortality risk in HD patients. Better survival was observed with UFR < 12.37 ml/h/kg BW. For patients with higher UFRs, longer or more frequent dialysis sessions should be considered in order to prevent the deleterious consequences of excessive UFR.     

Effects of respiration on the velocity of tricuspid regurgitation and estimation of systolic pulmonary artery pressure in patients with right ventricle systolic dysfunction

Objective. We investigated the effects of quiet respiration on the peak velocity of tricuspid regurgitation (TR) and estimation of systolic pulmonary artery pressure (SPAP) in patients with right ventricle (RV) systolic dysfunction using Doppler echocardiography. Methods. Continuous-wave Doppler spectra of TR were recorded in 32 patients with and 28 controls without RV systolic dysfunction. Electrocardiography and respiratory tracing were recorded simultaneously. Expiratory and inspiratory peak velocities of TR were acquired and averaged for five consecutive respiratory cycles. The SPAP during expiration and inspiration was calculated. Results. The velocity of TR and SPAP was not significantly different between expiration and inspiration in controls (2.77 ± 0.23 and 2.82 ± 0.26 m/s, P = 0.776; 35.94 ± 4.96 and 36.18 ± 5.12 mmHg, P = 0.747), whereas the velocity of TR and SPAP decreased significantly from expiration to inspiration in patients with RV systolic dysfunction (3.27 ± 0.35 and 2.59 ± 0.22 m/s, P < 0.001; 53.72 ± 7.39, 38.45 ± 5.63 mmHg, P < 0.001). Conclusions. Quiet respiration has significant effects on the velocity of TR in patients with RV systolic dysfunction. This factor should be taken into account when using Doppler echocardiography to estimate these patients’ SPAP, and the measurements should be performed in patients at the end of expiration.     

Clinical characteristics and mortality in hepatitis C-positive haemodialysis patients: a population based study.

BACKGROUND: The association between hepatitis C virus (HCV) infection and clinical and laboratory measures in maintenance haemodialysis (MHD) patients are poorly understood. METHODS: We analyzed data from over 37,000 MHD patients who underwent MHD for at least 3 months in DaVita dialysis clinics across USA in July 2001. RESULTS: The presence of HCV infection was determined using enzyme immunoassay (EIA), which was performed in 2778 MHD patients and was positive in 363 (13%) individuals. In a multivariate logistic regression model that adjusts for case-mix and available surrogates of malnutrition-inflammation complex syndrome (MICS), the following were independent predictors of HCV infection: younger age, male gender, Black race, Hispanic ethnicity, higher haemoglobin, lower serum albumin, higher total iron binding capacity, higher creatinine, and higher serum glutamic oxaloacetic transaminase (SGOT). Among receiver operating characteristics of commonly measured laboratory values in this population, the SGOT had the highest area. An SGOT > or =25 u/l had an adjusted odds ratio of 4.96 (95% confidence interval: 3.75-6.57) for HCV antibody positivity (sensitivity 50%, specificity 87%). HCV EIA positivity among MHD patients younger than 65 years was associated with 40-80% higher hazard ratio of all-cause and cardiovascular death during the 2 year follow-up (July 2001 to June 2003) after adjustment for case-mix and measures of MICS. CONCLUSION: HCV infection, as diagnosed by EIA, has distinct racial, age and laboratory predilections in MHD patients. HCV positivity among MHD patients younger than 65 years is associated with significantly higher cardiovascular mortality. More diligent HCV detection and treatment may improve cardiovascular survival in MHD patients.     

The prognostic impact of fluctuating levels of C-reactive protein in Brazilian haemodialysis patients: a prospective study.

BACKGROUND: A single elevated C-reactive protein (CRP) value predicts mortality in haemodialysis (HD) patients, but the relative importance of repeated vs occasional positive systemic inflammatory response findings is not known. METHODS: To assess the influence on survival of occasional inflammation, CRP, serum albumin (S-Alb) and fibrinogen were analysed bimonthly in 180 HD patients (54% male, 49+/-14 years). Clinically significant inflammation was defined as CRP >5.1 mg/l, based on the receiver operating characteristics curve for CRP as predictor of death. Based on four consecutive measurements of CRP, patients were assigned into three groups: group 1 (n = 74; 41%), no inflammation (CRP < or = 5.1 mg/l in all measurements); group 2 (n = 65; 36%), occasional inflammation (1-3 measurements of CRP > 5.1 mg/l); and group 3 (n = 41; 23%), persistent inflammation (all measurements of CRP >5.1 mg/l). The nutritional status was evaluated by subjective global assessment (SGA) and body mass index (BMI), and the survival (21 months of follow-up) by Kaplan-Meier curve and Cox model. RESULTS: The median and range of CRP values (mg/l) for group 1, 2 and 3 were: 3.2 (3.2-5.1), 3.6 (3.2-54.9) and 13.8 (5.2-82), respectively (P<0.001), whereas the prevalence of malnutrition, assessed by SGA and BMI, did not differ significantly between the groups. The survival rate by Kaplan-Meier analysis was significantly different among the groups (chi2 = 12.34; P = 0.0004). Patients in group 3 showed the highest mortality (34%; P = 0.001), compared with group 1 (8%) and group 2 (14%; P = 0.01), respectively, whereas there was no significant difference in mortality between groups 1 and 2. Age, CRP, S-Alb level and SGA were independent predictors of mortality. CONCLUSION: The patients with a persistent elevation of CRP had a higher mortality rate than the patients with occasional CRP elevation. Thus, persistent, rather than occasional, inflammation is an important predictor of death in HD patients.     

Inferior vena cava diameter: a useful method for estimation of fluid status in children on haemodialysis.

BACKGROUND: An accurate assessment of fluid status in haemodialysis patients presents a significant challenge especially in growing children. Clinical parameters of hydration are not always reliable, and invasive methods such as measurement of central venous pressure cannot be used routinely. We evaluated the usefulness of inferior vena cava diameter (IVCD) measured by echocardiography in the estimation of hydration in children on haemodialysis. METHODS: Fifteen haemodialysis patients (mean age 14 years) were evaluated. Clinical assessment included patients' symptoms, weight, blood pressure, heart rate, presence of oedema and vascular congestion, before and after dialysis session. Dry weight was assessed based on the above parameters. Fifty-two echocardiographic studies immediately prior and 30-60 min following dialysis were performed. The anteroposterior IVCD was measured 1.5 cm below the diaphragm in the hepatic segment in supine position during normal inspiration and expiration. IVCD was expressed per body surface area. RESULTS: Following haemodialysis mean IVCD (average of expiration and inspiration) decreased from 1.12+/-0.38 to 0.75+/-0.26 cm/m(2) (P<0.0001). Changes in IVCD were significantly correlated with alterations in body weight following dialysis (P<0.0001). The collapse index (per cent of change in IVCD in expiration vs inspiration) increased significantly after dialysis (P=0.035). IVCD clearly reflected alterations in fluid status. It did not vary significantly with changes in dry weight in a given patient. CONCLUSIONS: Our findings support the applicability of VCD measurement in the estimation of hydration status in paediatric haemodialysis patients. The combination of clinical parameters and measurement of IVCD may enable more accurate evaluation of hydration of children on haemodialysis.     

An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate.

BACKGROUND: Hyperphosphataemia contributes to secondary hyperparathyroidism and renal osteodystrophy in patients with end-stage renal disease (ESRD). Calcium salts are widely employed to bind dietary phosphate (P) but they may promote positive net calcium balance and metastatic calcification. We recently reported that ferric compounds bind intestinal phosphate in studies of normal and azotemic rats. METHODS: To extend this observation, we performed an open-label, random order, crossover comparison study of ferric citrate and calcium carbonate in haemodialysis patients from two teaching hospitals. The study sample consisted of 23 women and 22 men with an average age of 52.5 +/- 11.8 (SD) years and an average weight of 54.5 +/- 10.7 kg. All forms of iron therapy were discontinued. Two weeks before the study, patients were instructed to discontinue all P-binding agents. The patients were randomly assigned to receive either calcium carbonate (3 g/day) or ferric citrate (3 g/day) for 4 weeks followed by a 2 week washout period, and then crossed over to the other P-binding agent for 4 weeks. RESULTS: From a baseline concentration of 5.6 +/- 1.5 mg/dl, the serum P increased during the washout period to 7.2 +/- 1.9 mg/dl prior to calcium carbonate treatment, and to 6.7 +/- 1.9 mg/dl prior to ferric citrate treatment. The serum P concentration fell significantly during treatment with both calcium carbonate (7.2 +/- 1.9 to 5.2 +/- 1.5 mg/dl, P<0.0001) and ferric citrate (6.7 +/- 1.9 to 5.7 +/- 1.6 mg/dl, P<0.0001). The results were not influenced by order of treatment. Under the conditions of the study protocol, ferric citrate was less effective than calcium carbonate at lowering the serum phosphate concentration. The serum Ca concentration increased during treatment with calcium carbonate but not ferric citrate. Ferric citrate treatment did not affect the serum concentration of aluminium. Ferric citrate treatment was associated with mild and generally tolerable gastrointestinal symptoms. CONCLUSION: Ferric citrate shows promise as a means of lowering the serum phosphate concentration in haemodialysis patients. Further studies are needed to find the optimal dose.