Standard Bicarbonate Hemodialysis Research Articles

#885 Combination of medium cut-off dialyzer membrane and diet modification to reduce serum concentrations of p-cresyl sulfate and indoxyl sulfate

Abstract Background and Aims Online hemodiafiltration (ol-HDF) may be considered currently as the best choice for chronic hemodialysis (HD) treatment, but medium cut-off (MCO) membranes may provide similar efficiency for larger and protein-bound toxin removal. P-cresyl sulfate (PCS) and indoxyl-sulfate (IS) concentration depends mainly on residual renal function and diet. Increased dietary fiber intake and short-chain fatty acid (SCFA) supplementation were associated with decreased production of PCS and IS. The aim of this study was to pragmatically combine MCO use with diet modification in an attempt to reduce serum concentration of PCS and IS and compare this strategy to online HDF use. Method We report preliminary results from a subset of a study sample with 42 chronic prevalent HD patients in a prospective randomized controlled interventional study. Two weeks after standard bicarbonate HD (BHD), patients were randomized to hemodialysis with MCO membrane (EXP group) or ol-HDF with a standard "high-flux" (HF) dialyzer membrane (CON group). After 4 weeks, both groups were supplemented by a change in the diet with increase of the daily intake of dietary fiber to 30g and addition of a SCFA propionate in the dose of 1g daily for 8 weeks. Two main outcomes were serum concentrations of PCS and IS. Measurements were taken at baseline (after 2 week wash-in period), after 4 weeks of the first intervention phase (MCO vs. ol-HDF; T1), after 8 weeks of the second intervention phase (fiber and SCFA supplementation; T2) and finally, after 4 weeks of wash-out period with BHD (T3). Results From 42 participants, 38 completed the study (63.2% men, 66.4±10.9 years, Charlson comorbidity index 5.7±2.3). In the CON group, serum concentrations of PCS (in μg/ml) were 36.8±19.6 (baseline), 36.9±20.8 (T1), 32.4±17.4 (T2) and 38.6±22.1 (T3). Serum concentrations of IS (in μg/ml) were 31.8±13.0 (baseline), 32.9±14.7 (T1), 29.5±9.1 (T2) and 35.5±16.8 (T3). In the EXP group, serum concentrations of PCS were 33.5± 16.6 (baseline), 35.9±17.8 (T1), 34.0±16.1 (T2) and 37.4±21.5 (T3). Serum concentrations for IS were 39.6±12.6 (baseline), 37.3±12.9 (T1), 42.3±13.5 (T2) and 41.0±12.8 (T3). Repeated measures ANOVA revealed no significant time*group interaction for PCS (F(1,33)=0.479, p=0.698, ŋ2=0.014) and IS (F(1,33)=2.392, p=0.073, ŋ2=0.068). There was a significant within-group increase in serum IS concentration between T2 and T3 in CON group (p=0.042). There was a trend towards a decrease in PCS concentration between T1 and T2 and increase between T2 and T3 in CON group. Conclusion The results of the study suggest both hemodialysis methods are equivalent in eliminating PCS and IS. Additional fiber and SCFA propionate supplementation did not decrease serum PCS and IS concentrations significantly, although there was a trend towards lower serums concentration of PCS after diet modification in CON group.

Toxin Removal and Inflammatory State Modulation during Online Hemodiafiltration Using Two Different Dialyzers (TRIAD2 Study).

Uremic toxins play a pathological role in atherosclerosis and represent an important risk factor in dialysis patients. Online hemodiafiltration (HDF) has been introduced to improve the clearance of middle- and large-molecular-weight solutes (>500 Da) and has been associated with reduced cardiovascular mortality compared to standard hemodialysis. This non-randomized, open-label observational study will explore the efficacy of two dialyzers currently used for online HDF, a polysulfone-based high-flux membrane, and a cellulose triacetate membrane, in hemodialysis patients with signs of middle-molecule intoxication or intradialytic hypotension. In particular, the two filters will be evaluated for their ability in uremic toxin removal and modulation of inflammatory status. Sixteen subjects in standard chronic bicarbonate hemodialysis requiring a switch to online HDF in view of their clinical status will be enrolled and divided into two treatment arms, according to the previous history of hypersensitivity to polysulfone/polyethersulfone dialysis filters and hypersensitivity to drugs or other allergens. Group A will consist of 16 patients without a previous history of hypersensitivity and will be treated with a polysulfone filter (Helixone FX100), and group B, also consisting of 16 patients, with a previous history of hypersensitivity and will be treated with asymmetric triacetate (ATA; SOLACEA 21-H) dialyzer. Each patient will be followed for a period of 24 months, with monthly assessments of circulating middle-weight toxins and protein-bound toxins, markers of inflammation and oxidative stress, lymphocyte subsets, activated lymphocytes, and monocytes, cell apoptosis, the accumulation of advanced glycation end-products (AGEs), variations in arterial stiffens measured by pulse wave velocity (PWV), and mortality rate. The in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers will also be investigated to examine the changes in angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile. The expected results will be a better awareness of the different effects of polysulfone gold-standard membrane for online HDF and the new ATA membrane on the removal of uremic toxins removal and inflammation due to blood–membrane interaction.

Single Session and Weekly Beta 2-Microglobulin Removal with Different Dialytic Procedures: Comparison between High-Flux Standard Bicarbonate Hemodialysis, Post-Dilution Hemodiafiltration, Short Frequent Hemodialysis with NxStage Technology and Automated Peritoneal Dialysis

Background: NxStage System One cycler (NSO) is a widespread system for home daily dialysis. Few data are available on the impact of this “low dialysate volumes system” on the removal rate of poorly diffusible, time-dependent solutes like β₂-microglobulin (β₂M). Methods: Single-session and weekly balances of β₂M were performed and compared in 12 patients on daily NSO, 13 patients on standard high-flux bicarbonate dialysis (BHD), 5 patients on standard post-dilution on line hemodiafiltration (HDF), and 13 patients on automated peritoneal dialysis (APD). Results: Intradialytic fall of plasma water β₂M levels (corrected for rebound) was 65.2 ± 2.6% in HDF, 49.8 ± 9.1% in BHD, and 32.3 ± 6.4% in NSO (p < 0.001 between all groups). Single treatment dialysate removal was much less in APD (19.4 ± 20.4 mg, p < 0.001) than in any extracorporeal technologies, and was less in NSO (126.2 ± 35.6 mg, p < 0.001) than in BHD (204.9 ± 53.4 mg) and HDF (181.9 ± 37.6 mg), with no differences between the latter 2; however weekly removal was higher in NSO (757.3 ± 213.7 mg, p < 0.04) than in BHD (614.8 ± 160.3 mg) and HDF (545.8 ± 112.8 mg). Extrapolated β2M adsorption to the membrane was negligible in BHD, 14.7 ± 9.5% of total removal in HDF and 18.3 ± 18.5% in NSO. Integration of single session data into a weekly efficiency indicator (K × t) showed total volume of plasma cleared in NSO (33.4 ± 7.7 L/week) to be higher than in BHD (26.9 ± 7.2 L/week, p < 0.01) and not different than in HDF (36.2 ± 4.7 L/week); it was negligible (3.2 ± 1.0) in APD. Conclusions: Weekly β₂M removal efficiency proved equal and highest in HDF and NSO (at a 6/week prescription), slightly lesser in BHD and lowest in APD.

Acetate-free, citrate-acidified bicarbonate dialysis improves serum calcification propensity-a preliminary study.

A novel in vitro test (T50 test) assesses ex vivo serum calcification propensity and predicts mortality in chronic kidney disease and haemodialysis (HD) patients. For the latter, a time-dependent decline of T50 was shown to relate to mortality. Here we assessed whether a 3-month switch to acetate-free, citrate-acidified, standard bicarbonate HD (CiaHD) sustainably improves calcification propensity. T50 values were assessed in paired midweek pre-dialysis sera collected before and 3 months after CiaHD in 78 prevalent European HD patients. In all, 44 were then switched back to acetate. Partial correlation was used to study associations of changing T50 and changing covariates. Linear mixed effect models were built to assess the association of CiaHD and covariates with changing T50. A significant intra-individual increase of serum calcification resilience was found after 3 months on CiaHD (206 ± 56 to 242 ± 56 min; P < 0.001), but not after switching back to acetate (252 ± 63 to 243 ± 64 min; n = 44; P = 0.29). CiaHD, Δ serum phosphate and Δ albumin but not Δ ionized calcium and magnesium were the strongest determinants of changing T50. Beneath T50, only serum albumin but not phosphate changed significantly during 3 months of CiaHD. CiaHD dialysis favourably affected calcification propensity as measured by the T50 test. Whether this treatment, beyond established phosphate-directed treatments, has the potential to sustainably tip the balance towards a more anti-calcific serum milieu needs to be further investigated.

Acid-base homeostasis during hemodialysis: New insights into the mystery of bicarbonate disappearance during treatment.

In patients receiving hemodialysis, it has long been recognized that much more bicarbonate is delivered during treatment than ultimately appears in the blood. To gain insight into this mystery, we developed a model that allows a quantitative analysis of the patient's response to rapid alkalinization during hemodialysis. Our model is unique in that it is based on the distribution of bicarbonate in the extracellular fluid and assesses its removal from this compartment by mobilization of protons (H+ ) from buffers and other sources. The model was used to analyze the pattern of rise in blood bicarbonate concentration ([HCO3- ]), calculated from measurements of pH and PCO2 , in patients receiving standard bicarbonate hemodialysis. Model analysis demonstrated two striking findings: (1) 35% of the bicarbonate added during hemodialysis was due to influx and metabolism of acetate, despite its low concentration in the bath solution, because of the rapidly collapsing gradient for bicarbonate influx. (2) Almost 90% of the bicarbonate delivered to the patients was neutralized by H+ generation. Virtually all the new H+ came from intracellular sources and included both buffering and organic acid production. The small amount of added bicarbonate retained in the extracellular fluid increased blood [HCO3- ], on average, by 6mEq/L in our patients. Almost all this rise occurred during the first 2hours. Thereafter, blood [HCO3- ] changed minimally and always remained less than bath [HCO3- ]. This lack of equilibrium was due to the continued production of organic acid. Release of H+ from buffers is a reversible physiological response, restoring body alkali stores. By contrast, organic acid production is an irreversible process during hemodialysis and is metabolically inefficient and potentially catabolic. Our analysis underscores the need to develop new approaches for alkali repletion during hemodialysis that minimize organic acid production.

PP.28.05] CHARACTERISTICS OF BLOOD PRESSURE IN PATIENTS UNDERGOING CHRONIC HEMODIALYISIS

Objective: Cardiovascular (CV) disease is the most important cause of morbidity and mortality among patients with chronic kidney disease particularly in those undergoing chronic hemodialysis (HD). Hypertension (HT), the most important CV risk factor is frequently present and has several particular characteristics. Our aim was to analyze characteristics of HT in our group 194 patients undergoing HD. Design and method: In this study we have analyzed characteristics of HT and arterial stiffness (i.e. PWV) in 194 patients (118 m, 83 w; mean age 63+/-15 y). All patients were dialyzed three times a week with standard bicarbonate hemodialysis solutions and synthetic dialyzers according to the recent international guidelines. All measurements were done mid week day. Blood pressure (BP) was measured with Omron M6 (after dialysis session), ABPM using Spacelab 90207 (24 h) and PWV (before dialysis session) was determined with Arteriograph. Results: Significant difference in BP values measured after dialysis and ABPM were found (day, night, for both systolic and diastolic BP). Only 6.6% patients were normotensive, 63.3% hypertensive, while white coat (WCH) and masked hypertension (MH) were diagnosed in 26.4% and 3.7%, respectively (no gender differences). There were no differences in BP values between men and women, but PWV > 10m/s were found more frequently in men than in women in (m vs. w 56.5% vs.39.7%;p = 0.049; 48.3% in total; 10.4 +/-1.9 vs.9.7+/-1.7;p < 0.01). In logistic regression age was the most important predictor for pathologic values of PWV. WCH had slightly higher values of PWV than normotensives (9.7 +/-2.0 vs.8.5+/-1.3; p = 0.09). PWV in MH was not different compared to the sustained HT (10.2+/-1.7). Non-dipping status was established in 45.3%, extreme dipping in 18.8%, and only 21.6% were dippers. Conclusions: Our results confirmed significant clinical value of ABPM in patients undergoing dialysis. Determination of WCH subjects and non-dippers is of utmost importance for everyday tailoring of therapy. Increased arterial stiffness should be considered as well.

PP.06.38

Objective: Arterial stiffness (AS) is significant independant cardiovascular (CV) risk factor in patients undergoing hemodilaysis (HD). Reports on impact of different vascular access on AS are inconclusive and our aim was to analyse whether patients with arteriovenous fistula (AVF) differ from those dialysed via central venous catheters (CVC) in markers of AS. Design and method: We have enrolled 230 HD patients (median 65 yrs. (IQR 61–76), men 52%, dialysis vintage 67 (24–120) months. Out of them 167 (72.6%) patients had AVF and 63 had CVCs. All patients were on erythropoietin therapy and on active vitamin D as recommended by guidelines. They were dialyzed with standard bicarbonate hemodialysis solutions and synthetic dialyzers, with blood flow rates of 300–350 ml/min and dialysate flow rates of 500–800 ml/min. We have assessed AS i.e. pulse wave velocity (PWV) and augmentation index (Aix) by Arteriograph device, blood pressure (BP) was measured with Omron M6 device by ESH/ESC guidelines. All measurements were performed before mid-week dialysis. Results: There were no differences in age, sex, body height, body mass index, hypertension, diabetes, smoking status, Kt/V, serum calcium and cholesterol between two group of patients. Patients with AVF had significantly higher ultrafiltration rates, hemoglobin, phosphates, CaxP and serum iron (p < 0.002) with longer dialysis vintage (p = 0.02) as well higher values of brachial and central systolic BP, pulse pressure, AIx and PWV (p = 0.004; p = 0.001; p < 0.001; p = 0.014;p = 0.058). Using multiple linear regression models, PWV was positively associated with central systolic BP, ultrafiltration and CaxP (p = 0.02; p = 0.009; p = 0.001), while AIx was positively associated with central systolic BP (p < 0.001), and negatively with CaxP, heart rate and systolic BP (p = 0.028; p < 0.001; p < 0.001). In multiple linear regression models the type of vasacular access was not associated with AS markers. Conclusions: Patients with AVF had higher AS. However, the type of vascular access was not independently associated with wither PWV or AIx. Based on our results it could be concluded that vascular access type does not have impact on CV risk by modifying AS markers.

Ranking of factors determining potassium mass balance in bicarbonate haemodialysis.

One of the most important pathogenetic factors involved in the onset of intradialysis arrhytmias is the alteration in electrolyte concentration, particularly potassium (K(+)). Two studies were performed: Study A was designed to investigate above all the isolated effect of the factor time t on intradialysis K(+) mass balance (K(+)MB): 11 stable prevalent Caucasian anuric patients underwent one standard (∼4 h) and one long-hour (∼8 h) bicarbonate haemodialysis (HD) session. The latter were pair-matched as far as the dialysate and blood volume processed (90 L) and volume of ultrafiltration are concerned. Study B was designed to identify and rank the other factors determining intradialysis K(+)MB: 63 stable prevalent Caucasian anuric patients underwent one 4-h standard bicarbonate HD session. Dialysate K(+) concentration was 2.0 mmol/L in both studies. Blood samples were obtained from the inlet blood tubing immediately before the onset of dialysis and at t60, t120, t180 min and at end of the 4- and 8-h sessions for the measurement of plasma K(+), blood bicarbonates and blood pH. Additional blood samples were obtained at t360 min for the 8 h sessions. Direct dialysate quantification was utilized for K(+)MBs. Direct potentiometry with an ion-selective electrode was used for K(+) measurements. Study A: mean K(+)MBs were significantly higher in the 8-h sessions (4 h: -88.4 ± 23.2 SD mmol versus 8 h: -101.9 ± 32.2 mmol; P = 0.02). Bivariate linear regression analyses showed that only mean plasma K(+), area under the curve (AUC) of the hourly inlet dialyser diffusion concentration gradient of K(+) (hcgAUCK(+)) and AUC of blood bicarbonates and mean blood bicarbonates were significantly related to K(+)MB in both 4- and 8-h sessions. A multiple linear regression output with K(+)MB as dependent variable showed that only mean plasma K(+), hcgAUCK(+) and duration of HD sessions per se remained statistically significant. Study B: mean K(+)MBs were -86.7 ± 22.6 mmol. Bivariate linear regression analyses showed that only mean plasma K(+), hcgAUCK(+) and mean blood bicarbonates were significantly related to K(+)MB. Again, only mean plasma K(+) and hcgAUCK(+) predicted K(+)MB at the multiple linear regression analysis. Our studies enabled to establish the ranking of factors determining intradialysis K(+)MB: plasma K(+) → dialysate K(+) gradient is the main determinant; acid-base balance plays a much less important role. The duration of HD session per se is an independent determinant of K(+)MB.

Congestive heart failure in patients with chronic kidney disease

Cardiovascular disorders are the most frequent cause of death (46-60%) among patients with advanced chronic renal failure (CRF), and on dialysis treatment. Uremic cardiomyopathy is the basic pathophysiologic substrate, whereas ischemic heart disease (IHD) and anemia are the most important contributing factors. Associated with well-know risk factors and specific disorders for terminal kidney failure and dialysis, the aforementioned factors instigate congestive heart failure (CHF). Suspected CHF is based on the anamnesis, clinical examination and ECG, while it is confirmed and defined more precisely on the basis of echocardiography and radiology examination. Biohumoral data (BNP, NT-proBNP) are not sufficiently reliable because of specific volemic fluctuation and reduced natural clearance. Therapy approach is similar to the one for the general population: ACEI, ARBs, β-blockers, inotropic drugs and diuretics. Hypervolemia and most of the related symptoms can be kept under control effectively by the isolated or ultrafiltation, in conjunction with dialysis, during the standard bicarbonate hemodialysis or hemodiafiltration. In the same respect peritoneal dialysis is efficient for the control of hypervolemia symptoms, mainly during the first years of its application and in case of the lower NYHA class (II°/III°). In general, heart support therapy, surgical interventions of the myocardium and valve replacement are rarely used in patients on dialysis, whereas revascularization procedures are beneficial for associated IHD. In selected cases the application of cardiac resynchronization and/or implantation of a cardioverter defibrillator are advisable.

Erythrocyte glutathione transferase: a new biomarker for hemodialysis adequacy, overcoming the Kt/Vurea dogma?

Kt/Vurea ratio is commonly used to assess the delivered dose of dialysis in maintenance hemodialysis (MHD) patients. This parameter only reflects the efficacy of dialytic treatments in removing small toxins, but not middle and protein-bound toxins. Erythrocyte glutathione transferase (e-GST), an enzyme devoted to cell depuration against a lot of large and small toxins, is overexpressed in uremic patients. Aim of the present study is to verify whether e-GST may represent a novel biomarker to assess the adequacy of different dialytic techniques complementary to Kt/Vurea parameter. Furthermore, it will be investigated whether e-GST could reflect the ‘average' adequacy of multiple dialytic sessions and not of a single one treatment as it occurs for Kt/Vurea. One hundred and three MHD patients and 82 healthy subjects were tested. Fourty four patients were treated with standard bicarbonate hemodialysis (HD) and 59 patients were on online hemodiafiltration (HDF). In all MHD patients e-GST activity was 60% higher than in healthy controls. In HDF, e-GST activity was lower than in HD subgroup (8.2±0.4 versus 10.0±0.4 U/gHb, respectively). Single-pool Kt/Vurea and total weekly Kt/Vurea were higher in HDF than in HD, but no correlation was found between e-GST activity and Kt/Vurea data. e-GST, whose level is stable during the erythrocyte life-span, provides information on the long-term depurative efficacy of dialysis treatments.

Variability of pulse wave velocity and mortality in chronic hemodialysis patients

We have already demonstrated that in chronic hemodialysis (HD) patients, the cyclic variations in both hydration status and blood pressure are responsible for changes in pulse wave velocity (PWV). The aim of this study is to verify whether the cyclic variation of PWV influences mortality in dialysis patients. We studied 167 oligoanuric (urinary output <500 mL/day) patients on chronic standard bicarbonate HD for at least 6 months. They performed 3 HD sessions of 4 hours per week. Patients were classified into 3 groups: normal PWV before and after dialysis (LL); high PWV before and normal PWV after dialysis (HL); and high PWV before and after dialysis (HH). The carotid-femoral PWV was measured with an automated system using the foot-to-foot method. Analysis of variance was used to compare the different groups. The outcome event studied was all-cause mortality and cardiovascular mortality. The PWV values observed were LL in 44 patients (26.3%); HL in 53 patients (31.8%); and HH in 70 patients (41.9%). The 3 groups of patients are homogenous for sex, age, and blood pressure. The HH group had a higher prevalence of (P<0.001) ASCVD. It is interesting that the distribution of patients in the 3 groups is correlated with the basal value of PWV. In fact, when the basal measure of PWV is elevated, there is a higher probability that an HD session cannot reduce PWV (<12 ms). A total of 53 patients (31.7%) died during the follow-up of 2 years: 5 patients in the LL group (11.4%); 16 in the HL group (30.2%); and 32 in the HH group (50.7%) (LL vs. HL, P=0.047; LL vs. HH, P<0.00001; HL vs. HH, P=0.034). We evidence for the first time that different behaviors of PWV in dialysis subjects determine differences in mortality.

Calcium mass balances during standard bicarbonate hemodialysis and long-hour slow-flow bicarbonate hemodialysis

Dialysate calcium (Ca) concentration should be viewed as part of the integrated therapeutic regimen to control renal osteodystrophy and maintain normal mineral metabolism. Thus, a correct ionized calcium mass balance (Ca++MB) during hemodialysis (HD) is crucial in the treatment of renal osteodystrophy. The GENIUS single-pass batch dialysis system (Fresenius Medical Care, Germany) consists of a closed dialysate tank of 90 L; it offers the opportunity of effecting mass balances of any solute in a very precise way. The present study has a crossover design: 11 stable anuric HD patients underwent 2 bicarbonate HD sessions, 1 of 4 hours (4h) and the other of 8 hours (8h) in a random sequence, always at the same interdialytic interval, at least 1 week apart. The GENIUS system and high-flux FX80 dialyzers (Fresenius Medical Care, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration and dialysate Ca concentrations (1.50 mmol/L) were prescribed to be the same. Trends of plasma Ca++, blood pH and bicarbonates during dialysis, as well as Ca++MBs were determined. Plasma parathyroid hormone (PTH) levels at the start and end of the 2 treatments were measured. Ca++MBs (mean ± SD) were +284.6 ± 137.4 mg and +297.7 ± 131.6 mg (p=0.307) in the 4h and 8h treatments, respectively. No single session out of the 22 had a negative Ca++MB for the patient. Mean plasma Ca++, blood pH and bicarbonate levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. Mean plasma Ca++, blood pH and bicarbonate levels increased significantly along the time points in both 4h and 8h HD sessions (repeated measures ANOVA: p<0.0001). Mean plasma PTH levels were not statistically significantly different when comparing the start and end of the sessions of the 2 treatments. The differences between predialysis and postdialysis plasma PTH levels were not statistically significantly different either in 4h or 8h sessions (Wilcoxon's test: p=NS), even though a trend toward lower postdialysis plasma PTH levels was observed in both 4h and 8h treatments. Our data show incontrovertibly that, when dialyzing with a dialysate Ca concentration of 1.50 mmol/L, 4h standard bicarbonate HD and 8h slow-flow bicarbonate HD always achieve a quite similar positive Ca++MB for the patients.

Removal of uraemic retention solutes in standard bicarbonate haemodialysis and long-hour slow-flow bicarbonate haemodialysis

Several studies already stressed the importance of haemodialysis (HD) time in the removal of uraemic toxins. In those studies, however, also the amount of dialysate and/or processed blood was altered. The present study aimed to investigate the isolated effect of the factor time t (by processing the same total blood and dialysate volume in two different time schedules) on the removal and kinetic behaviour of some small, middle and protein-bound molecules. The present study had a crossover design: 11 stable anuric HD patients underwent two bicarbonate HD sessions (~ 4 and ~ 8 h) in a random sequence, at least 1 week apart. The GENIUS single-pass batch dialysis system and the high-flux FX80 dialysers (Fresenius Medical Care, Bad Homburg, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration, and dialysate composition were prescribed to be the same. For each patient, blood was sampled from the arterial line at 0, 60, 120, 180 and 240 min (all sessions), and at 360 and 480 min (8-h sessions). Dialysate was sampled at the end of HD from the dialysate tank. The following solutes were investigated: (i) small molecules: urea, creatinine, phosphorus and uric acid; (ii) middle molecule: β(2)M; and (iii) protein-bound molecules: homocysteine, hippuric acid, indole-3-acetic acid and indoxyl sulphate. Total solute removals (solute concentration in the spent dialysate of each analyte × 90 L - the volume of dialysate) (TSR), clearances (TSR of a solute/area under the plasma water concentration time curve of the solute) (K), total cleared volumes (K × dialysis time) (TCV), and dialyser extraction ratios (K/blood flow rate) (ER) were determined. The percent differences of TSR, K, TCV and ER between 4- and 8-h dialyses were calculated. Single-pool Kt/Vurea, and post-dialysis percent rebounds of urea, creatinine and β(2)M were computed. TSR, TCV and ER were statistically significantly larger during prolonged HD for all small and middle molecules (at least, P < 0.01). Specifically, the percent increases of TSR (8 h vs 4 h) were: for urea 22.6.0% (P < 0.003), for creatinine 24.8% (P < 0.002), for phosphorus 26.6% (P < 0.001), and for β(2)M 39.2% (P < 0.005). No statistically significant difference was observed for protein-bound solutes in any of the parameters being studied. Single-pool Kt/Vurea was 1.41 ± 0.19 for the 4-h dialysis sessions and 1.80 ± 0.29 for the 8-h ones. The difference was statistically significant (P < 0.0001). Post-dialysis percent rebounds of urea, creatinine and β(2)M were statistically significantly greater in the 4-h dialysis sessions (at least, P < 0.0002). The present controlled study using a crossover design indicates that small and middle molecules are removed more adequately from the deeper compartments when performing a prolonged HD, even if blood and dialysate volumes are kept constant. Hence, factor time t is very important for these retention solutes. The kinetic behaviour of protein-bound solutes is completely different from that of small and middle molecules, mainly because of the strength of their protein binding.

Haemodynamic consequences of changing bicarbonate and calcium concentrations in haemodialysis fluids

Background. In a previous study we demonstrated that mild metabolic alkalosis resulting from standard bicarbonate haemodialysis induces hypotension. In this study, we have further investigated the changes in systemic haemodynamics induced by bicarbonate and calcium, using non-invasive procedures.Methods. In a randomized controlled trial with a single-blind, crossover design, we sequentially changed the dialysate bicarbonate and calcium concentrations (between 26 and 35 mmol/l for bicarbonate and either 1.25 or 1.50 mmol/l for calcium). Twenty-one patients were enrolled for a total of 756 dialysis sessions. Systemic haemodynamics was evaluated using pulse wave analysers. Bioimpedance and BNP were used to compare the fluid status pattern.Results. The haemodynamic parameters and the pre-dialysis BNP using either a high calcium or bicarbonate concentration were as follows: systolic blood pressure (+5.6 and −4.7 mmHg; P < 0.05 for both), stroke volume (+12.3 and +5.2 ml; P < 0.05 and ns), peripheral resistances (−190 and −171 dyne s cm−5; P < 0.05 for both), central augmentation index (+1.1% and −2.9%; ns and P < 0.05) and BNP (−5 and −170 ng/l; ns and P < 0.05). The need of staff intervention was similar in all modalities.Conclusions. Both high bicarbonate and calcium concentrations in the dialysate improve the haemodynamic pattern during dialysis. Bicarbonate reduces arterial stiffness and ameliorates the heart tolerance for volume overload in the interdialytic phase, whereas calcium directly increases stroke volume. The slight hypotensive effect of alkalaemia should motivate a probative reduction of bicarbonate concentration in dialysis fluid for haemodynamic reasons, only in the event of failure of classical tools to prevent intradialytic hypotension.

Chronic inflammation and mortality in haemodialysis: effect of different renal replacement therapies. Results from the RISCAVID study

The 'RISchio CArdiovascolare nei pazienti afferenti all' Area Vasta In Dialisi' (RISCAVID) study is an observational and prospective trial including the whole chronic haemodialysis (HD) population in the northwest part of Tuscany (1.235 million people). The aim of the study was to elucidate the relevance of traditional and non-traditional risk factors of mortality and morbidity in HD patients as well as the impact of different HD modalities. A total of 757 HD patients (mean age 66 +/- 14 years, mean dialytic age 70 +/- 76 months, diabetes 19%) were prospectively followed up for 30 months and all-cause mortality, cardiovascular (CV) mortality and non-fatal CV events (acute myocardial infarction and stroke) were registered. At the time of the enrolment, demographic, clinical and laboratory data of the whole population were entered into a centralized database. Serum albumin, high-sensitive C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-8 (IL-8) were centrally determined at the start of the study. Patients were stratified into three groups according to the HD modality: standard bicarbonate HD (BHD) (n = 424), haemodiafiltration (HDF) with sterile bags (n = 204) and online HDF (n = 129). The Cox proportional hazards regression assessed adjusted differences in CV morbidity and mortality risk; a multivariate analysis was also performed. All-cause and CV mortality was 12.9%/year and 5.9%/year, respectively. Patients with combined high levels of CRP and pro-inflammatory cytokines showed an increased risk for CV (RR 1.9, P < 0.001) and all-cause mortality (RR 2.57, P < 0.001). Multivariate analysis adjusted for comorbidity and demographic showed CRP as the most powerful mortality predictor (P < 0.001) followed by IL-6. The Cox proportional hazards regression assessed that online HDF and HDF patients had a significantly increased adjusted cumulative survival than BHD (P < 0.01). Data at 30 months from this study showed the synergic effect of CRP and pro-inflammatory cytokines as the strong predictors of all-cause and CV mortality. HDF was associated with an improved cumulative survival independent of the dialysis dose.

Role of B-Type Natriuretic Peptide in Cardiovascular State Monitoring in a Hemodialysis Patient with Primary Amyloidosis

Cardiac involvement occurs in up to 50% of patients with primary or A amyloidosis (ALA) and is associated with very poor prognosis. B-type natriuretic peptide (BNP) has been proposed as a guide for treatment of heart failure patients and as an index of myocardial dysfunction in patients with ALA. Data about BNP dosage for cardiovascular monitoring of patients with ALA on renal replacement therapy are lacking. A 64 year old Caucasian man was admitted because of nephrotic syndrome in July 2003. Renal diagnosis was ALA. Melphalan and prednisolone were given but renal function worsened and in April 2004 standard bicarbonate hemodialysis was started. In March 2004 thalidomide was added to his therapy. During the follow-up ejection fraction was stable and was 65% on the contrary E/A ratio gradually increased and overtook 1. BNP plasma levels were increased and the values recorded during the follow-up were: 2505 pg/mL in October 2003 (normal reference values<100), 1827 in April 2004, 4006 in June 2004, 5000 in September 2004, 3750 in January 2005 and 1920 in April 2005. In September 2005 BNP was 3380 pg/mL. The patient was still alive after a follow-up longer than two years. In ALA patients a powerful prognostic role of BNP has been reported whose expression is increased in ventricular myocytes of patients with cardiac involvement. BNP level monitoring does not appear to be superior to standard echocardiography in evaluating cardiovascular status of uremic patients with ALA.

Does Bicarbonate Transfer Have Relevant Hemodynamic Consequences in Standard Hemodialysis?

Background: In a previous study we demonstrated that mild metabolic alkalosis resulting from standard bicarbonate hemodialysis induces hypotension. This study aimed to compare hemodynamic consequences of either a decrease in the dialysate bicarbonate from 32 to 26 mmol/l or an increase in the dialysate calcium of 0.25 mmol/l and to verify whether the calcium shift secondary to alkalemia explains the consequences on blood pressure. Methods: In this randomized controlled trial with a single-blind, cross-over design, we used dialysis liquids with two different bicarbonate (32 mmol/l in modalities A and C, and 26 mmol/l in modality B) and calcium (1.25 mmol/l in modalities A and B, and 1.50 mmol/l in modality C) concentrations, and in 27 patients, 243 dialysis sessions, compared blood pressure, heart rate and the incidence of hypotension. Results: No significant differences were seen between A and B while an increase in systolic and diastolic blood pressures and a decrease in the incidence of hypotension (10.5 vs. 1.2%, p < 0.05) were documented in C. The subgroup of patients who with A showed a lower mean systolic blood pressure received more angiotensin-converting enzyme inhibitors or angiotensin II type-1 receptor blockers (36 vs. 0%, p <0.05) and in C showed a less important increase in systolic and diastolic pressures, but the incidence of hypotensive episodes between A and B was not significantly different (9.1 vs. 15.1%). Conclusions: In the present study it was not possible to demonstrate hemo dynamic instability associated with mild metabolic alkalosis. Even in the subgroup showing a lower blood pressure with a higher dialysate bicarbonate, significant hemodynamic or clinical consequences were not noticed. The calcium shift (0.05 mmol/l) related to alkalemia would justify a mean decrease in systolic blood pressure of only about 1 mm Hg.

Clinical evaluation of internal hemodiafiltration (iHDF): a diffusive-convective technique performed with internal filtration enhanced high-flux dialyzers.

Efficiency in removing middle molecules such as beta2-microglobulin (beta2-MG) is one of the main purposes of modern dialytic therapy. In order to achieve this, techniques requiring complex machines and substitution fluid have been developed over recent years. Alternatively, the internal filtration/back filtration phenomenon can be used. The recent development of a so-called "internal filtration enhanced dialyser" prompted us to compare the removal of beta2-MG together with other small molecules when the dialyser was used either in standard hemodiafiltration (HDF) or internal hemodiafiltration (iHDF). Ten stable, anuric, hemodialysis (HD) patients treated by thrice weekly standard bicarbonate HD using low-flux synthetic membrane entered the study. A new high-flux polysulfone dialyser designed with the specific aim of enhancing internal filtration (BS-1.6 UL, 1.6 m2, Toray Industries) was used. Post dilution HDF (2.5 l/hour of substitution fluid, dialysate flow 500 ml/min) was compared with iHDF (dialysate flow 750 ml/min), with blood flow at 300 ml/min. Samples were obtained at the start and at the end of the session in order to measure the % removal of urea, creatinine, uric acid, phosphate and beta2-MG (corrected for total protein concentration). In addition, after 20 min of dialysis the clearances of the same molecules were measured. A mathematical model has been developed for the description of the hydrodynamic phenomena taking place within the dialyser and of fluid filtration across the membrane. No significant differences have been observed in removal rate switching from HDF to iHDF except for beta2-MG removal, which was slightly higher in HDF than in iHDF Phosphate clearance is significantly higher than those obtained with creatinine in both HDF (p<0.005) and iHDF (p<0.01) modalities. The total convection calculated with the model is reduced with respect to HDF only by 24% (4100 ml/h vs. 5400 ml/h on the average). iHDF is a high flux dialysis method, which, if performed with a dialyser designed to enhance internal filtration, obtains a much higher removal rate in comparison with dialysers in traditional high flux dialysis, as previously reported in the literature. Provided that the dialyser is used on a dialysis machine working with ultra pure dialysate and UF control, this dialyser line can perform reliable internal HDF without the need for replacement solution. Considering the narrow difference in performance observed between iHDF and HDF, and the increasing number (and age) of patients leading to higher dialysis costs, iHDF represents a cost-effective alternative to other diffusive-convective techniques.

Rinsing Dialyzers without Heparin in Hemodialysis (HD) with Low-Molecular Weight Heparin (LMWH)

Saline plus unfractionated heparin (UFH) is routinely used for priming dializers before HD start. The aim of this study is to assess if heparin is necessary in pre-rinsing procedure of extracorporeal systems, anticoagulated with LMWH. We carried-out a prospective study in 14 stable HD patients, aged 58.5 ± 3.6 years old. All patients were treated by standard bicarbonate HD, 3 sessions × week, HD time 220 ± 12 min, Qb 276 ± 21 ml/min, low-flux dialyzers (polisulfone 5, cellulose diacetate 9). Clotting was prevented with a single bemiparin (LMWH) bolus 2900 ± 140 IU. Three rinsing protocols were applied in three consecutive weeks: 1st week- Saline 1000 ml + LMWH 2500 IU. 2d week- Saline 1000 ml + UFH 5000 IU. 3th week- Saline 1000 ml. Anti-Xa activity (IU/ml) was measured at each HD (at 10 min/end). Clotting events and post-HD AVF hemostasis were recorded in a semiquantitative scale. No significant statistical differences (Anova) were found in anti-Xa heparin activity (IU/ml) among the three rinsing protocols tested: 10 min (NS) End (NS) 1st week 0.81 ± 0.16 0.55 ± 0.43 2nd week 0.76 ± 0.21 0.58 ± 0.16 3th week 0.86 ± 0.14 0.64 ± 0.16 No differences were observed in drip chamber or dialyzer appearance after HD. Massive clotting was not recorded. No important bleeding was observed at stick needle sites. In conclusion, HD performed with LMWH no needs heparin in rinsing solution. The procedure is effective and safe.

Abnormalities of bioimpedance measures in overweight and obese hemodialyzed patients

The body composition in overweight and obese hemodialyzed patients (HD) remains ill-defined. This study evaluates in HD patients the influence of body size, as indicated by body mass index (BMI, kg/m(2)), on body composition by measuring bioimpedance analysis (BIA)-derived variables (phase angle (PA), fat-free mass (FFM) and body cell mass (BCM). We studied 50 Caucasian patients (mean age 62.8+/-9.2 y) on standard bicarbonate hemodialysis for at least 12 months who regularly achieved dry weight in post-HD, received similar dialysis doses and were free from inflammation/infection. Thirty-eight gender- and age-matched healthy subjects were included as controls (CON). Both HD and CON were divided into three groups on the basis of their BMI(kg/m2) 18.5-24.9, normal-weight (NW); 25-29.9, overweight (OW); and > or =30, obese (OB). In HD patients, BIA was performed 30 min after the end of dialysis. Seven patients were obese (12%) while 16 were overweight (32%); in CON, 12 were obese (31%) and 12 overweight (31%). BIA-measured extracellular water was comparable in all groups. PA, which was similar in normal-weight HD and CON (6.2+/-0.9 degrees and 6.3+/-0.8 degrees ), decreased in OW- and OB-HD patients (5.3+/-1.0 degrees and 5.2+/-0.6 degrees, respectively; P<0.05 vs NW-HD) while it was unchanged in OW- and OB-CON (6.1+/-0.8 degrees and 5.9+/-0.5 degrees, P<0.05 vs respective HD groups). In OW and OB patients, the lower PA values were coupled with a major reduction of BIA-derived percentage BCM and FFM (P<0.05 vs NW-HD, and vs OW- and OB-CON). In patients, PA and BCM correlated with anthropometry-measured FFM. Of note, serum albumin and protein catabolic rate were significantly reduced in OB patients. In overweight and obese HD patients, BIA-derived FFM, BCM and PA are significantly lower with respect to normal-weight patients and BMI-matched controls. These abnormalities of body composition are coupled with reduction of anthropometric measures of lean mass and a decrease of protein intake that, however, becomes significant only in the obese. We therefore suggest that overweight and obese HD patients are at risk of protein malnutrition in spite of excessive energy intake. BIA may be considered as a useful diagnostic tool to detect such a condition early.