The association of overhydration with megafistulas in hemodialysis patients.

Objectives: Diffuse enlargements of arteriovenous dialysis fistulas customarily attributed to either excessive arterial inflow or central outflow stenosis. The relationship between volume status and clinically enlarged (arteriovenous) fistula (CEF) formation in end-stage renal disease (ESRD) patients is not well understood. Methods: We assessed the pre-dialysis bioimpedance spectroscopy-measured percentage of overhydration (OH%) in 13 prevalent dialysis patients with CEF development and negative angiography and compared the results with those of 52 control dialysis patients (CONTR). All patients were prevalent ESRD patients receiving thrice-weekly maintenance hemodiafiltration at an academic outpatient dialysis unit. Results: 10/13 CEF patients had OH% ≥15% as compared to 20/52 control patients (Chi square p: .02). The degree of OH% was 20.2 ± 7.4% among the CEF vs. 14.4 ± 7.1% in the control group (Student's t-test p: .01), representing 4.2 ± 3.2 vs. 2.8 ± 1.6 L of excess fluid pre-dialysis (p: .03). Patients with CEF development took an average of 1.7 ± 1.4 vs. 0.8 ± 0.8 (p: .002) antihypertensive medications compared to the CONTR patients, yet their blood pressure was higher: 156/91 vs. 141/78 mmHg (systolic/diastolic p: .03<.0001). We found no difference in fistula vintage, body mass index, age, diabetes status, or diuretic use. The odds ratio of having a CEF in patients with ≥15% OH status was 5.3 (95% CI: 1.3-21.7; p: .01), the Number Needed to Harm with overhydration was 4. Conclusions: There is an association between bioimpedance spectroscopy-measured overhydrated clinical state and the presence of CEF; either as an increased volume capacitance or as a potential cause.

The effect of ambient temperature and humidity on interdialytic weight gains in end-stage renal disease patients on maintenance hemodialysis.

PURPOSE: Interdialytic weight gain (IDWG) is both a measure of dietary compliance and a well-established predictor of future adverse outcomes in dialysis patients. The impact of environmental conditions on IDWG in end-stage renal disease is little studied to date. METHODS: We retrospectively reviewed IDWG for 100 consenting chronic end-stage renal disease patients undergoing thrice weekly in-center hemodiafiltration under three different climatic conditions in a Central European city: Weekend_1 was humid (93 %) and warm (24 °C); Weekend_2 was dry (38 %) and hot (33 °C); and Weekend_3 was dry (30 %) and warm (24 °C). RESULTS: The cohort's mean age was 60.9 ± 14.7 years, all were Eastern European, and 56 % were men. Residual urine output measured 100 [25-75 % quartiles: 0, 612] mL/day, single-pool Kt/V 1.4 ± 0.25, and albumin 40.1 ± 3.9 g/L. Mean IDWGs measured as follows: Weekend_1 ("humid-warm"): 2973 ± 1386 mL; Weekend_2 ("dry-hot"): 2685 ± 1368 mL and Weekend_3 ("dry-warm"): 2926 ± 1311 mL. Paired-samples testing for difference showed higher fluid gains on the humid-warm (239 mL; 95 % CI 21-458 mL; p = 0.032) and on the dry-warm weekends (222 mL; 95 % CI -8 to 453 mL, p = 0.059), when compared to the dry-hot weekend. Under the latter, dry-hot climatic condition, residual urine output lost its significance to impact IDWG during multiple regression analysis. CONCLUSION: While excess temperature may impact IDWG to a small degree, air humidity does not; the least weight gains occurred on the dry-hot weekend. However, the effects of both were minimal under continental summer conditions and are unlikely to explain large excesses of individual session-to-session variations.

Diuretics and bioimpedance-measured fluid spaces in hypertensive patients.

The authors examined the relationship between thiazide-type diuretics and fluid spaces in a cohort of hypertensive patients in a retrospective study of 60 stable hypertensive patients without renal abnormalities who underwent whole-body bioimpedance analysis. Overhydration was greater in the diuretic group, but only to a nonsignificant degree (5.9 vs. 2.9%; P=.21). The total body water did not differ in the two groups (41.8 L vs. 40.5 L; P=.64). Extracellular fluid volume (ECV) (19.7 L vs. 18.5 L; P=.35) and intracellular fluid volume (ICV) spaces (20.8 L vs. 21.3 L; P=.75) were also not significantly different in the two groups. The ratio of ICV:ECV, however, appeared different: 1.05 vs 1.15 (P=.017) and the effect was maintained in the linear regression-adjusted model (ß coefficient: -0.143; P=.001). The diuretic-related distortion of ICV:ECV ratio indicates potential fluid redistribution in hypertensive patients, with ICV participating in the process.

Impact of hemodialysis, left ventricular mass and FGF-23 on myocardial mechanics in end-stage renal disease: a three-dimensional speckle tracking study.

Left ventricular (LV) hypertrophy and one of its inducers, the fibroblast growth factor-23 (FGF-23) were found to be associated with unfavourable outcome in end-stage renal disease (ESRD) patients. We sought to investigate the influence of hemodialysis (HD), increased LV mass and FGF-23 on LV mechanics using three-dimensional (3D) speckle tracking echocardiography. Forty-four ESRD patients on maintenance HD were examined just before and immediately after HD, and were compared to 44 normal controls (NC). Transthoracic 3D recordings were obtained using multi-beat reconstruction from 6 consecutive cardiac cycles. LV mass index (LVMi) was evaluated and 3D speckle tracking analysis was performed to calculate global longitudinal (GLS), circumferential (GCS), area (GAS) and radial (GRS) peak systolic strain. Serum FGF-23 levels were also measured. Strain values improved in all directions after HD [pre- vs. post-HD; GLS: -20(3) vs. -21(6), GCS: -20(4) vs. -22(7), GAS: -33(5) vs. -35(10), GRS: 50(12) vs. 53.5(20) %, all p < 0.01]. LVMi was remarkably increased in our patients [ESRD vs. NC; 136(46) vs. 71(8) g/m(2), p < 0.001]. Elevated FGF-23 levels were associated with increased LV mass (ρ = 0.581, p < 0.001). LVMi was inversely related to pre-HD GCS (ρ = 0.626, p < 0.001) and post-HD GCS (ρ = 0.761, p < 0.001), GAS (ρ = 0.534, p < 0.05) and GRS (ρ = -0.639, p < 0.01). Serum FGF-23 levels correlated with post-HD GAS (ρ = 0.513, p < 0.01) and GRS (ρ = -0.512, p < 0.05). HD treatment results in immediate improvement in all strain directions. Besides inducing LV hypertrophy, FGF-23 may play a role in the deterioration of LV mechanics in patients with ESRD.

Which fluid space is affected by ultrafiltration during hemodiafiltration?

Ultrafiltration (UF) is a common procedure performed during almost all dialysis sessions. During UF, several liters of fluid are removed; however, what proportion of this fluid is removed from which fluid space could not be clinically measured easily until now; we designed this study to evaluate the fluid spaces most affected by UF. This is a prospective cohort study of 40 prevalent chronic hemodialysis patients receiving thrice weekly hemodiafiltration (HDF). We measured the patients' fluid spaces using a whole-body bioimpedance apparatus to evaluate the changes of fluid spaces before and immediately after the HDF sessions. We recorded the data on fluid spaces, UF volume, and blood pressures. The cohort consisted of 40 prevalent HDF patients, aged 60.0 ± 5.2 years (37.5% men; 27.5% people with diabetes), and body weight 71.03 ± 15.48 kg. Achieved UF was 2.38 ± 0.98 L on HDF (measured fluid overload: 2.35 ± 1.44 L). The extracellular fluid (EC) volume decreased from 16.84 ± 3.52 to 14.89 ± 3.06 L (P < 0.0001) and intracellular fluid (IC) volume from 16.88 ± 4.40 to 16.55 ± 4.48 L (P = 0.45). Although urea volume of distribution remained effectively unchanged (31.38 ± 7.28 vs. 30.70 ± 7.32 L; P = 0.45), the degree of EC volume overload decreased from 13.60% ± 7.30% to 3.83% ± 8.32% (P < 0.0001). The mean arterial pressure also decreased from 122.95 ± 19.02 to 108.50 ± 13.91 mmHg (P < 0.0001). We conclude that source of net fluid loss by ultrafiltration is almost exclusively the EC fluid space. The intracellular fluid space is not significantly affected immediately after HDF.

Volume estimation in dialysis patients: the concordance of brain-type natriuretic peptide measurements and bioimpedance values.

Correct estimation of the dialysis patients' hydration status remains an important clinical challenge. Bioimpedance measurements have been validated by various physiological tests, and the use of brain-type natriuretic peptide (BNP) has been validated by inferior vena cava diameter measurements. This is an observational cohort study that evaluated the correspondence between bioimpedance-measured overhydration percentage (OH%) and BNP. We measured predialysis OH% by bioimpedance apparatus (Body Composition Monitor) and BNP by microparticle enzyme-linked immunoassay in 41 prevalent stable hemodialysis patients, 19 (46%) women, aged 58.9 ± 14.5 years. The cohort's average BNP was 2694 ± 3278 pg/mL and 10 (24.4%) of these 41 patients had BNP < 500 pg/mL (average 260.7 ± 108.5). The OH% was 8.5 ± 7.0% among those with a BNP < 500 pg/mL, while the rest of the population had an OH% of 21.4 ± 8.0%, corresponding to excess volumes of 1.6 ± 1.3 and 4.4 ± 3.8 L, respectively. The OH% vs. BNP relationship was best described by the exponential regression of y = 216.4e(0.097x) , predicting a BNP of 216.4 pg/mL at 0% overhydration status (r 0.61). Receiver-operating curves revealed an area under the curve of 0.885 for BNP when the OH% was set ≥15% of overhydration and an area under the curve of 0.918 for OH% when the BNP was set ≥500 pg/mL for being abnormal. We conclude that in our cohort there was a high degree of correspondence between these two tests with an exponential relationship between the measurements.

Switching between parathormone (PTH) assays: the impact on the diagnosis of renal osteodystrophy.

BACKGROUND: Clinical guidelines for decision-making in chronic kidney disease (CKD) consider parathormone (PTH) levels. The measured PTH values differ if novel full length PTH(1-84) assays are used instead of earlier intact iPTH assays. In this study we analyzed how the classification of CKD patients alters when iPTH assays are switched to PTH(1-84) assays. METHODS: Plasma samples were collected prior to dialysis sessions from 110 consecutive CKD patients on maintenance hemodialysis. PTH levels were determined with iPTH assays (Elecsys, Architect and DiaSorin Liaison N-tact) and PTH(1-84) assays (Elecsys and Liaison). Using KDIGO guidelines patients were classified as being below, above and in the recommended target range (RTR) of PTH. The results of classification with different assays were evaluated and, a novel calculation method of RTR was implemented. RESULTS: The prevalence of patients with PTH in RTR is comparable with each assay, but the individual patients differed. PTH(1-84) Elecsys and Liaison assays classified more patients as being below RTR than iPTH Elecsys and Architect but not Liaison N-tact assay (27.3%, 22.7% vs. 41%, 31.8%, and 36.4%, respectively). In turn, PTH(1-84) Elecsys and Liaison assays identified less CKD patients with PTH above the RTR than iPTH except N-tact assays (6.4%, 10% vs. 16.3%, 19%, and 6.3%, respectively). Using our calculation method, our discrimination values for PTH(1-84) assays to achieve classification identical to that with iPTH Elecsys were lower than those recommended by the manufacturer. CONCLUSIONS: Current guidelines for the treatment of secondary hyperparathyroidism in CKD should consider the type of assays used for PTH measurement. Each laboratory should assess its own RTR for PTH tests to achieve comparable classification. The presented calculation is simple, it mimics an everyday situation, switching from one assay to another one, and provides useful RTR values for PTH tests.

Dialysate saving by automated control of flow rates: comparison between individualized online hemodiafiltration and standard hemodialysis.

Cost reduction and quality improvement seem to be conflicting issues. However, online hemodiafiltration (oHDF) with new automatic functions offers a cost-efficient therapy compared to hemodialysis (HD). Seven dialysis centers conducted a randomized clinical trial with cross-over design: high-flux HD vs. postdilutional oHDF with functions coupling both dialysate and substitution flow rates to blood flow rates. During the 6 weeks of the study, all treatment parameters remained unchanged for HD and oHDF, apart from dialysate and substitution flow rate. Treatment data were recorded during each treatment, and predialytic and postdialytic concentrations of urea were recorded at the end of each study phase. The analysis involved 956 treatments of 54 patients. The mean dialysate consumption was 123.2 ± 6.4 l for HD and 113.4 ± 14.9 l for oHDF (p < 0.0001), the mean dialysis dose was 1.42 ± 0.23 for HD and 1.47 ± 0.26 for oHDF (p < 0.0001); oHDF resulted in a lower dialysate consumption (8.0% less) and a slightly increased dialysis dose (Kt/V 3.5% higher) compared to HD. oHDF with the investigated automatic functions offers substantial savings in dialysate consumption without decreasing dialysis dose.

Dialysis patients' fluid overload, antihypertensive medications, and obesity.

Overhydration (OH) is both a major etiology of hypertension in hemodialysis patients and a serious risk factor for mortality. We investigated the association of multiple variables and OH. This is a cross-sectional study of prevalent hemodialysis patients examining the predialysis hydrational status with a portable bioimpedance apparatus to measure the degree of hydration. We completed our study in 79 patients. Patients were overhydrated by 2.6 ± 2.4 L. The mean medication count was 2.4 ± 1.5, and 50.7% had diuretics. We found a significant correlation between OH and systolic blood pressure (r = 0.39; p = 0.0006), each liter of OH generating 3.6 mm Hg. We also found a positive correlation between the use of diuretics and OH (p = 0.003, two-tailed Student's t test) but no correlation between OH and body weight (r < 0.0001; p = 0.99), body mass index (r = -0.17), age (r = 0.089), and vintage (r = 0.05). For every 10% increase in body fat, OH decreased by 1.2 L; residual urine output gave no protection from OH (r = 0.077) and did not correlate with blood pressure (r = 0.01). Overhydration is strongly associated with the use of antihypertensive medications and the use of diuretics in this dialysis population. Obesity seems to afford some protection from OH.

Polymorphisms of the ApoE, HSD3B1, IL-1beta and p53 genes are associated with the development of early uremic complications in diabetic patients: results of a DNA resequencing array study.

Genetic polymorphisms of the genes involved in angiogenesis, the inflammatory cascade or apoptosis control can influence the chronic complications of diabetic patients. Parallel evaluation of multiple genetic polymorphisms became available with the development of DNA resequencing arrays. We aimed to develop a 16-gene, 18,859-nucleotide resequencing array to analyze the genetic background of uremic and gastrointestinal complications. DNA was isolated from 10 ml of peripheral blood of 41 non-uremic and 37 uremic patients with type II diabetes mellitus (DM); 32 suffering from gastric erosion complications. An Affymetrix Customseq Resequencing array was developed containing a total of 37 PCR products of selected genes. Confirmatory analysis was performed for 5 known polymorphisms by RFLP and for 4 others by capillary sequencing. Statistical analysis was performed using the Fisher's exact test. Correlations between the DNA resequencing array and the confirmatory methods were 96% for RFLP and 99.4% for capillary sequencing. The genetic polymorphisms of the ApoE, HSD3B1, IL-1beta and p53 genes were found to be significantly different (p<0.05) between the uremic and non-uremic diabetes group. In regards to the gastric erosion complications of the diabetic uremic patients, the A17708T polymorphism of the p53 intron 10 was found to have a statistically significant (p<0.05) role. In conclusion, DNA sequencing arrays can contribute to a multiparameter genetic analysis yielding highly correlating results using a single method in patients suffering type II DM.

On-line haemodiafiltration versus haemodialysis: stable haematocrit with less erythropoietin and improvement of other relevant blood parameters.

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 x 24 weeks at a dialysis dose of eKt/V> or =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.

[Role of autologous antebrachial arteriovenous fistula for vascular access in hemodialysis]. / Proximális radio-cephalikus autológ fisztulák szerepe a hemodialízis-kezelés biztosításában.

Numbers of arteriovenous (AV) fistula creation increase worldwide. Hemodialysis is more effective, patients live longer, they need more access operation. 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 radio-cephalic 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. At our department the performance of autogenous fistulas have always been favoured. Beside the wrist radio-cephalic and elbow fistulas a significant number of autologous forearm AV fistulas has been operated. Our aim was to study the short and long term results of the autogenous forearm fistulas at atypical anatomic positions. We also examined whether the patency rate is affected by different variables as diabetes mellitus, acute or chronic operative situation, the indication of surgery, the quality of thrill at the end of shunt creation, the diameter and quality of the vein. Between 1997 and 2005 we performed 1018 AV shunts in an academic tertiary care center. 97 autologous antebrachial AV shunts were performed. The average follow up time was 31.3 months. The primary patency rate was 97%, 92% and 63% at the end of the first, second and sixth years, respectively. The patency rate was not significantly affected by any of the examined variables mentioned above. 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. More proximal autologous fistulas and prosthetic graft implantation could be postponed, this way valuable time could be saved for the uremic patients.

On-line hemodiafiltration does not induce inflammatory response in end-stage renal disease patients: results from a multicenter cross-over study.

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.

Autonomic dysfunction in uremia assessed by heart rate variability.

Decreased heart rate variability is an independent risk factor for cardiac mortality in hemodialysis patients. Our aim was to determine whether it is already present in uremic children and young adults on hemodialysis and following renal transplantation. Twenty-two hemodialysis patients [age 17.2 years (median, quartiles 13.0-22.6)], 22 transplant patients [18.4 years (14.4-21.2)], and 29 healthy controls [16.4 years (15.7-21.1)] were examined. Heart rate and its high (HF) and low (LF) frequency variability were measured in the supine position for 10 min. High and low frequency variability was significantly reduced, whereas heart rate and LF/HF ratio was significantly elevated in both patient groups compared with controls. There was a clear-cut difference between the dialyzed and the transplanted groups based on the HF variability, with the lowest values in the dialysis group ( P<0.01). LF and LF/HF data did not allow us to distinguish between the patient groups. In conclusion, heart rate variability in the HF range is a sensitive tool for detecting cardiovascular autonomic dysfunction that is already present in children and adolescents with impaired kidney function.