Background: Cardiovascular diseases are the leading causes of morbidity and mortality in patients with chronic renal insufficiency. We sought to investigate the chronic renocardiac syndrome and the immediate effects of hemodialysis (HD) on myocardial mechanics using three-dimensional (3D) speckle tracking echocardiography. Methods: Forty-four patients (mean age 48±13 years, 54% men) with end-stage renal disease on three times per week maintenance HD, without diabetes and any significant cardiac disease were investigated just before and immediately after HD, and compared to 46 normal controls (NC; 48±12 years, 48% men). Beyond conventional transthoracic echocardiographic examination, 3D recordings were obtained using multi-beat reconstruction from 6 consecutive cardiac cycles (GE Vivid E9). Ejection fraction (EF) and left ventricular mass indexed to body surface area (LVMi) were measured, and 3D speckle tracking analysis was performed to assess global longitudinal-, circumferential-, area- and radial peak systolic strain values (GE 4D Auto LVQ). For statistical analysis, Wilcoxon signed-rank, Mann-Whitney U, Spearman correlation tests and multivariate linear regression were used. Data are presented as median (interquartile range). Results: LVMi was remarkably increased in patients compared to NC [136 (46) vs. 71 (8) g/m2, p<0.001]. EF and strain values in all directions improved after HD [pre- vs. post-HD; EF: 63 (9.5) vs. 66 (10), longitudinal: -20 (3) vs. -21 (6), circumferential: -20 (4) vs. -22 (7), area: -33 (5) vs. -35 (10), radial: 50 (12) vs. 53.5 (20) %, all p<0.01]. While there was no difference in longitudinal strain, the patients' pre-HD circumferential, area and radial strains were reduced, and after HD only the circumferential strain increased enough to be similar compared to NC [NC longitudinal: -20.5 (3), circumferential: -21 (3), area -36 (3), radial 61 (8) %, p<0.05]. LVMi correlated inversely with post-HD circumferential strain (ρ=0.34, p<0.05), and even stronger with area (ρ=0.54) and radial strains (ρ=-0.58, both p<0.001). In a multivariate linear regression model, circumferential strain was found to be an independent predictor of EF both before (β=-0.88, p<0.001) and after HD (β=-0.96, p<0.001). Conclusions: In chronic renocardiac syndrome the left ventricle can be characterized by increased mass and reduced 3D strain values measured by speckle tracking echocardiography. The increase of LVMi correlates strongly with the reduction of area and radial strains. HD results in immediate improvement of left ventricular function indicated by EF and 3D strain, as well.

Purpose: In patients with chronic renal insufficiency traditional risk factors of left ventricular (LV) hypertrophy include hypertension, overhydration, anemia and impaired calcium-phosphate homeostasis. Fibroblast growth factor 23 (FGF-23) is a phosphaturic hormone secreted by osteoblasts and a rising biomarker associated with LV hypertrophy and mortality in patients with end-stage renal disease (ESRD). We sought to determine the relationship between serum FGF-23 levels and left venticular mass measured by three-dimensional (3D) echocardiography in ESRD patients. Methods: This retrospective cohort study included 44 patients (mean age 48±13 years, 54% men) with ESRD on three times per week maintenance hemodialysis. Exclusion criteria were previous history of diabetes and any significant cardiac disease. Beyond conventional transthoracic echocardiographic examination, 3D recordings were obtained using multi-beat reconstruction from 6 consecutive cardiac cycles (GE Vivid E9). After semi-automated tracing of LV endo- and epicardial surface at end-diastolic frame, LV mass was calculated using dedicated software (GE 4D Auto LVQ). Serum FGF-23 levels were measured by enzyme-linked immunosorbent assay (Merck Millipore). Overhydration evaluated by bioimpedance (Fresenius Body Composition Monitor), laboratory test results (including serum calcium, phosphate, parathormone, total iron binding capacity levels) and blood pressure were recorded and averaged in the three previous months. Relationships were calculated by Spearman correlation test and multivariate linear regression. Results: The median value of LV mass measured in ESRD patients was 244 grams (interquartile range 97.5). Serum FGF-23 levels ranged between 34 and 6848 with a median of 687 pg/ml. Serum levels of FGF-23 (ρ=0.52), phosphate (ρ=0.55), parathormone (ρ=0.38), total iron binding capacity (ρ=0.61), systolic blood pressure (ρ=0.38) and pulse pressure (ρ=0.47, all p<0.05) correlated significantly with LV mass. FGF-23 correlated with serum phosphate (ρ=0.83) and parathormone (ρ=0.53, both p<0.001) levels. In a multivariate linear regression model, FGF-23 (β=0.42, p<0.001), total iron binding capacity (β=0.49, p<0.001) and systolic blood pressure (β=0.37, p<0.01) were found to be independent predictors of LV mass. Conclusions: To the best of our knowledge, this is the first study which demonstrates the strong correlation between serum FGF-23 levels and LV mass measured by 3D echocardiography. Beside the chronic volume- and pressure overload, LV hypertrophy is strongly determined by the endocrine effects of FGF-23 in patients with ESRD.

Background The incidence of fractures is substantially increased in patients with chronic kidney disease (CKD) compared to the general population. The factors associated with increased bone fracture in this population are not well understood. Vitamin D deficiency has been associated with decreased bone mass and higher incidence of fractures in the general population. In this study, we aimed to assess the association between fracture and vitamin D status and other factors potentially associated with fracture in patients on maintenance hemodialysis. Methods One hundred and forty-four patients were assessed and interviewed about previous low-trauma fractures. Evidence of fracture was obtained from medical records and also through patient interviews. Routine laboratory results were collected from medical records. Serum intact PTH (iPTH) and 25(OH) vitamin D 3 were measured. All patients underwent bone densitometry of the lumbar spine, femoral neck and distal radius. Bone quality was also assessed with quantitative bone ultrasound (QUS). Descriptive statistics, logistic regression models were used to analyze factors associated with fractures. Results One hundred and thirty patients were included in the final analysis. Patients with fractures ( n = 21) had lower 25(OH) vitamin D 3 levels (15.8 nmol/l (interquartile range, IQR: 27) vs. 30.0 nmol/l (IQR: 28.5), P = 0.029), were more likely females, had longer duration of end-stage kidney disease, and lower bone mineral density (BMD) at the distal radius. QUS parameters were not associated with fractures. Multivariate analyses revealed that serum 25(OH) vitamin D 3 concentration, BMD at the radius, iPTH less than 100 pg/ml and history of fractures were independent predictors of new bone fracture after the initiation of dialysis therapy. Conclusion Increased bone fragility in dialysis patients is associated with vitamin D deficiency and relative hypoparathyroidism in addition to reduced BMD at the radius. Further studies are needed to determine whether patients with vitamin D deficiency benefit from vitamin D supplementation to reduce fracture risk.

The relationship between parathyroid function, an important determinant of bone turnover, and bone mineral density (BMD) in patients with chronic kidney disease is not fully understood. We wanted to analyze the association between BMD and parathyroid function in hemodialysis patients in details.

BACKGROUND:Resistance to erythropoiesis-stimulating agents (ESAs) has been observed in patients with chronic kidney disease (CKD) and it is associated with clinical outcomes. The presence of ESA resistance cannot always be explained by the known risk factors of the condition, suggesting that additional factors may be involved. We wanted to test the hypothesis that vitamin D insufficiency is associated with lower hemoglobin (Hb) and ESA resistance in patients on maintenance hemodialysis (HD).METHODS:Data from patients receiving maintenance HD in a single dialysis center were extracted from the medical records in a retrospective chart review. Basic patient characteristics and laboratory data including Hb, serum albumin, intact parathyroid hormone and serum 25(OH)-cholecalciferol (25(OH)D(3)) levels were collected. ESA dose and Kt/V were extracted from the dialysis charts. Correlation analysis and multivariate linear regression analysis were used to reveal potential independent associations between clinical and laboratory parameters and ESA resistance.RESULTS:Data from 142 patients were analyzed. Serum 25(OH)D(3) concentration was significantly correlated with Hb (ρ = 0.186, p < 0.05) and also with ESA dose/Hb index (ρ = 0.230, p < 0.01). In multivariable regression analyses, serum 25(OH)D(3) concentration remained significantly associated with both Hb and ESA dose/Hb index after controlling for potentially important confounders.CONCLUSION:Serum 25(OH)D(3) concentration is independently associated with erythropoietin responsiveness in CKD patients on maintenance HD. If this association will be confirmed, treatment trials looking at the effect of vitamin D supplementation on anemia treatment in CKD patients may be warranted.

AIM:The number of arteriovenous (AV) fistula creation increases worldwide. Haemodialysis is more effective, patients live longer, and they need more access operations. The optimal strategy for the order and sequence of the different type and localization of AV fistulas remains obscure. Based on internationally acclaimed guidelines, autogenous access should be performed whenever possible and the first operation of choice is the radiocephalic fistula at the wrist, the second type is the elbow fistula. The area between the standard exposures means also good access area and its usage is not emphasized properly. Our aim was to study the short and long-term the results of autologous forearm fistulas.METHODS:Between 1997 and 2005 we performed 1018 AV shunts in an academic tertiary care centre. Ninety-seven autologous antebrachial AV shunts were performed. The average follow-up time was 31.3 months. We examined the patency rate and its connection with different variables such as diabetes mellitus, acute or chronic operative situations, indications for surgery, diameter and quality of the vein.RESULTS:The primary patency rates were 93%, 79.5% and 61.2% at the end of years 1, 2 and 6, respectively. The patency rate was not significantly affected by any of the examined variables mentioned above.CONCLUSION:The patency rate of the autologous antebrachial AV shunt is comparable to the wrist and elbow fistulas, so our results support the practice of performing fistula at this atypical localization. Proximal autologous fistulas and prosthetic graft implantation could be postponed, this way valuable time could be saved for the uremic patients.

Background: Controlled randomised studies to prove improved cardiovascular stability and improved anaemia management during on-line haemodiafiltration (oHDF) are scarce. Methods: 70 patients were treated with both haemodialysis (HD) and oHDF in a cross-over design during 2 × 24 weeks at a dialysis dose of eKt/V≧1.2. Patients randomised into group A started on HD and switched over to oHDF, whereas patients in group B began with oHDF and were treated with HD afterwards. Intradialytic morbid events (IME), such as symptomatic hypotension or muscle cramps, were noted in case of appearance. Blood parameters reflecting anaemic status, phosphate status, lipid metabolism, oxidative stress, and accumulation of advanced glycation end products were recorded either monthly or at the end of each study phase. Results: The mean incidence of IME was 0.15 IME per treatment, and there was no statistical difference between oHDF and HD. A higher haematocrit (oHDF 31.5% vs. HD 30.5%, p < 0.01) at a lower erythropoietin dose (oHDF 4,913 vs. HD 5,492 IU/week, p = 0.02) was found during oHDF, when the sequence of HD and oHDF had not been taken into account. For the study groups, the results were less distinct: in group A, a higher haematocrit (HD 30.4% vs. oHDF 32.0%, p < 0.01) at a comparable erythropoietin dose (HD 5,421 vs. oHDF 5,187 IU/week, ns) was observed during oHDF, whereas in group B an identical haematocrit (oHDF 30.8% vs. HD 30.7%, ns) was achieved at a reduced erythropoietin dose (oHDF 4,622 vs. HD 5,568 IU/week, p < 0.01). During oHDF, lower levels of free and protein-bound pentosidine and of serum phosphate were found. Conclusion: In contrast to other studies, no benefit regarding cardiovascular stability for oHDF was found, but oHDF could well offer a potential benefit regarding anaemia correction, inflammation, oxidative stress, lipid profiles, and calcium-phosphate product.

AIMS:An increasing amount of evidence suggests that 25-hydroxy vitamin D3 (25(OH)D3) may contribute to the bone health of patients with chronic kidney disease (CKD). The underlying vitamin D status of these patients, however, has often been neglected. In a cross-sectional study we assessed the association between vitamin D status and parathyroid function, bone turnover, bone mass and structure in patients on maintenance hemodialysis.METHODS:69 patients on maintenance hemodialysis were assessed by bone densitometry (DEXA) and quantitative bone ultrasound (QUS). Serum 25-hydroxy vitamin D3 levels, serum markers of bone turnover and clinical data were tabulated.RESULTS:A high prevalence of potentially significant vitamin D3 deficiency was found in this patient group: 59% of the patients had a 25(OH)D3 level below 20 nmol/l. There was a significant negative correlation between serum 25(OH)D3 levels and serum intact parathyroid hormone (iPTH) (r = -0.231, p < 0.05), and this association remained significant after controlling for potential covariables. Furthermore, we show here that serum 25(OH)D3 concentration is positively correlated with bone mineral density (BMD) measured at the radius (r = 0.424, p < 0.01). Finally, we show for the first time that 25(OH)D3 levels are significantly and independently correlated with broadband ultrasound attenuation (beta = 0.262, p < 0.05) measured with calcaneal quantitative bone ultrasound (QUS) in patients with chronic renal failure.CONCLUSION:Vitamin D3 deficiency may contribute to the impaired bone health of patients on maintenance dialysis.

BACKGROUND:On-line hemodiafiltration (HDF) represents the supreme blood purification modality for end-stage renal disease (ESRD) patients. Large-volume infusion of on-line prepared substitution fluid may, however, expose patients to inflammatory contaminants. As a result, on-line HDF might aggravate chronic inflammation, which correlates with malnutrition, cardiovascular disease, and mortality among ESRD patients.METHODS:In a multicenter cross-over study, 27 ESRD patients were randomly assigned to treatment with on-line HDF and low-flux hemodialysis (HD). After 6 months, patients were crossed to the other treatment modality, and treatment continued for another 6 months. Both on-line HDF and low-flux HD were conducted with polysulfone membranes and ultrapure dialysis fluid. Samples were drawn at the end of each treatment period.RESULTS:Inflammatory parameters were elevated in the study population when compared to healthy controls. Induction of interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor alpha (TNF-alpha) was comparable for on-line HDF and low-flux HD, and there was no intradialytic increase in cytokine production. As a result, interleukin-6 (IL-6) plasma levels did not differ significantly between the two treatment modalities. Similarly, no difference between on-line HDF and low-flux HD was observed for C-reactive protein (CRP) and albumin. Markers of endothelial cell activation (soluble intercellular and vascular cell adhesion molecules sICAM-1 and sVCAM-1) as well as the cardiovascular risk marker cardiac troponin T (cTnT) remained elevated compared to healthy subjects, but showed no difference between the two treatment modalities.CONCLUSIONS:On-line HDF, as the most effective renal replacement therapy, does not provoke inflammatory response and is both safe and highly biocompatible.

BACKGROUND:Low heart rate variability (HRV) is an independent risk factor of cardiac mortality in patients with end-stage renal disease (ESRD). It has been explained by uremic parasympathetic neuropathy. Sympathetic overactivity can also reduce HRV. Our aim was to determine whether there is vagal activity in ESRD patients that is masked by sympathetic activity.METHODS:The effect of propranolol on HRV was examined in 13 patients with ESRD, aged 20.1 +/- 7.6 years without diabetes. All patients were given intravenous propranolol (0.05 mg/kg) once and placebo once in a randomized, double-blind way, with an interval of 6.6 days (mean, range: 2-9). Propranolol was administered before hemodialysis treatment, after 40 minutes supine resting period. HRV was registered for 10 minutes, during supine, before and after the injection. Patients' HRV data were compared to that of 29 age-matched healthy controls.RESULTS:Initially, both high-(HFV) and low-frequency (LFV) bands of heart rate variability were lower in ESRD patients compared to controls (p < 0.001 for both). Propranolol resulted in a significant increase of HFV (propranolol: AlgHFV = 0.182 (0.027 - 0.337), placebo: deltalgHFV = -0.029 (-0.128 - +0.070); p = 0.032). Elevation of LFV was not significant. Six patients had an elevated plasma norepinephrine and/or epinephrine level. Plasma dopamine level was elevated in all but 1 patient (mean: 432 pmol/l, 95% CI: 320-543) and showed an inverse relationship with the increase of IgHFV secondary to propranolol (r = -0.66, p = 0.014).CONCLUSIONS:Low HFV of ESRD patients can be improved by beta-adrenergic blockade. It demonstrates that there is some vagal activity in ESRD that is masked by sympathetic activity. Therefore, altered sympathovagal balance of ESRD patients should be taken into consideration in the assessment of vagal uremic neuropathy.