Acetate-free Dialysate Research Articles

MON-110 Effect of the acid of dialysate on survival in the French REIN registry

We previously found a reduced mortality associated with the use of acetate free dialysate (AFD) in subjects older than 70 years old. As the use of these dialysates made with hydrochloric (HCl) or citric acid steadily increases since 2010, we wonder whether this result can be reproduced in the last recent years. All patients who started HD from 2010 to 2013 were classified according to their exposure to the different types of dialysate in their dialysis unit. Cox survival analysis was performed in 25,629 incident patients being alive after 3 months of dialysis, adjusted for 14 baseline co-morbidities, biological data and 4 technical data and accounting for patient clustering within facilities. Dialysate exposure was analyzed as a time-dependent variable taking into account the changes of dialysate in the dialysis unit and the changes of dialysis center of each patient. Analysis was censored at Dec 31, 2014, or at kidney transplantation, loss to follow-up, dialysis weaning and transfer to peritoneal dialysis or home hemodialysis. Among the 25 629 included subjects, 17 747 started dialysis in centers using standard dialysate, 7358 in centers using both standard and AFD and 524 in centers using only AFD. The percentage of dialysis centers using exclusively standard dialysate dwindled from 74% in 2010 to 25% in 2014. Overall mortality HR of being dialyzed in a unit using both acetate and HCl was estimated to 0.86 [0.76 - 0.98] compared to the standard centers. On the contrary, during exposition in a mixed unit using both acetate and citrate, the all-cause mortality risk was multiply by 1.44 [1.33 -1.55]. The calcium dialysate load also varies between the different dialysates, citrate dialysate bringing calcium similarly to an acetate dialysate having a 0.15 mmol/L higher calcium concentration. We additionally adjusted the all-cause mortality Cox models for the calcium dialysate concentration after reclassifying calcium concentration of citrate dialysate and found similar results. Using an entirely new data set of subjects exposed to AFD in the REIN registry, we confirm that being dialyzed with HCl dialysate is associated with a reduced mortality risk but being dialyzed with citrate dialysate seemed deleterious. The difference in calcium load between citrate and acetate dialysate didn't explain this result.

Comparison of Sustained Low‐Efficiency Dialysis With Acetate‐Free and Acetate‐Containing Bicarbonate Dialysate in Unstable Patients

This work is focused on the problem of maintenance of intradialytic hemodynamic safety in unstable patients with acute kidney injury (AKI). A hypothesis that "small" quantities of acetate in standard bicarbonate dialysate can cause pronounced acetatemia and exacerbate cardiovascular instability was tested. In this prospective randomized study, a group of patients with AKI after cardiac surgery was treated with sustained low-efficiency dialysis with either acetate-containing bicarbonate dialysate or acetate-free dialysate, where acetate is replaced by hydrochloric acid. It was demonstrated that application of acetate-containing bicarbonate dialysate results in blood acetate levels up to 12 times the normal level. Additionally, it is associated with a 3.8-fold-increased risk of hemodynamic complications in comparison with acetate-free dialysate. The choice of acetate-free or acetate-containing bicarbonate dialysate does not influence adequacy of correction of the acid-base and electrolyte content of blood.

Effects of Acetate‐Free Citrate‐Containing Dialysate on Metabolic Acidosis, Anemia, and Malnutrition in Hemodialysis Patients

Previously, dialysate contained small amounts of acetate as an alkaline buffer. Recently, acetate-free dialysate (A[-]D) has been available. We evaluated the clinical effect of A(-)D over acetate-containing dialysate (A(+)D) on acid-base balance, anemia, and nutritional status in maintenance hemodialysis (MHD) patients. Twenty-nine patients on MHD were treated with A(+)D for 4 months (first A(+)D), switched to A(-)D for 4 months, and returned to A(+)D for the next 4-month period (second A(+)D). Metabolic acidosis: Serum bicarbonate (HCO3(-) ) levels did not change in patients with normal HCO3(-) levels (≥20 mEq/L) throughout the study. Meanwhile, in patients with initially low HCO3(-) levels, it was significantly increased during the A(-)D period only. Anemia: In patients with target hemoglobin (Hb) ≥10 g/dL, Hb levels were maintained during the study period, even if the dose of erythropoiesis-stimulating agents (ESAs) decreased. In patients with low Hb levels, it was significantly increased in the A(-)D period without increasing ESA or iron doses. Nutritional Condition: In patients with normal albumin levels (≥3.8 g/dL), albumin did not change throughout the study period. However, in patients with lower albumin levels, it was significantly increased during the A(-)D period. These improvements in metabolic acidosis, anemia, and nutrition in the A(-)D period completely dissipated during the second A(+)D period. Hemodialysis (HD) with A(-)D may improve a patient's clinical status with intractable metabolic acidosis, hyporesponsiveness to ESA, and malnutrition that were not normalized in HD with A(+)D.

Comparison of Sustained Hemodiafiltration with Acetate-Free Dialysate and Continuous Venovenous Hemodiafiltration for the Treatment of Critically Ill Patients with Acute Kidney Injury

We conducted a prospective, randomized study to compare conventional continuous venovenous hemodiafiltration (CVVHDF) with sustained hemodiafiltration (SHDF) using an acetate-free dialysate. Fifty critically ill patients with acute kidney injury (AKI) who required renal replacement therapy were treated with either CVVHDF or SHDF. CVVDHF was performed using a conventional dialysate with an effluent rate of 25 mL·kg−1 · h−1, and SHDF was performed using an acetate-free dialysate with a flow rate of 300−500 mL/min. The primary study outcome, 30 d survival rate was 76.0% in the CVVHDF arm and 88.0% in the SHDF arm (NS). Both the number of patients who showed renal recovery (40.0% and 68.0%, CVVHDF and SHDF, resp.; P < .05), and the hospital stay length (42.3 days and 33.7 days, CVVHDF and SHDF, resp.; P < .05), significantly differed between the two treatments. Although the total convective volumes did not significantly differ, the dialysate flow rate was higher and mean duration of daily treatment was shorter in the SHDF treatment arm. Our results suggest that compared with conventional CVVHDF, more intensive renal support in the form of post-dilution SHDF with acetate-free dialysate may accelerate renal recovery in critically ill patients with AKI.

Efficacy of acetate-free dialysate for the treatment of patients with acute kidney injury

Efficacy of acetate-free dialysate for the treatment of patients with acute kidney injury

PHF on-line sin acetato: cómo mejorar la hiperacetatemia y la tolerancia hemodinámica

The small quantity of acetate present in the dialysis fluid exposes patient's blood to an acetate concentration 30-40 times the physiological levels. This amount is even greater in hemodiafiltration on-line. Our purpose was to evaluate the clinical-analytical effects using three different dialysis techniques in the same patient. 35 patients on hemodialysis were included. All patients were treated with conventional bicarbonate dialysate for 3 months, after randomization were switched to first be treated with PHF online with standard bicarbonate dialysate for 6 months and then switched to PHF on-line acetate-free dialysate for the other 6 months or to invert the two last periods. Blood samples were drawn monthly throughout the study and clinical data were obtained. Postdialysis blood acetate levels were higher in patients treated with conventional bicarbonate dialysate with respect to the period of PHF with free-acetate dialysate. Moreover, the percentage of patients with postdialysis blood acetate levels in the pathologic range was higher in patients treated with conventional bicarbonate dialysate respect to PHF on-line acetate-free dialysate period (61% vs. 30%). Serum concentrations of chloride postdialysis were higher and serum concentrations of bicarbonate pre and posthemodialysis were lower in the PHF free-acetate period. The incidence of hypotensive episodes was significantly lower in the PHF on-line with conventional dialysate. PHF on-line with free-acetate dialysate allows that most of patients finished hemodialysis with blood acetate levels in the physiologic ranges. PHF on-line is a predilutional hemodiafiltration treatment with better tolerance than hemodialysis with standard bicarbonate dialysate.

Duocart Biofiltration

DuoCart biofiltration (DCB) is a new hemodialysis method using a dialysate with only sodium chloride and bicarbonate obtained from two separate powder cartridges (BiCart and SelectCart, Gambro, Sweden). The ionic complement is directly reinfused in postdilution mode, using one 2 L bag of a specially designed sterile solution. The adaptation of the quantity of these infused substances to their removal through the dialysis membrane is made possible by repeated measurements of ionic dialysance (D), which are automatically performed every 30 min by the Diascan module, systematically available on the Integra dialysis monitor (Hospal, Italy), and by subsequent modification of the infusion rate (Q(R)). An appropriate kinetic model was used to determine the composition of the reinfusion solution (mM: 57 K, 47 Ca, 14.5 Mg, 180 Cl), the conductivity dialysate (set at 14.8 mS/cm) and the ratio Q(R)/D (set at 1/28). This ratio is kept constant by updating Q(R) after each measurement of D. The implementation of this technique requires an Integra dialysis monitor equipped with a two-powder-cartridge dialysate generation system. Fifteen dialysis sessions were performed (duration: 213+/-38 min; blood flow: 238+/-26 ml/min; ultrafiltration rate: 16+/-6 ml/min). The per-dialytic changes of ion plasma concentrations were monitored and found to be within the predicted range. The results substantiate the feasibility of this new hemodialysis method that presents several advantages: dialysate concentrates are in powder form, an alkaline and acetate-free dialysate is used with superior dialysate biocompatibility, no precipitation of Ca and Mg carbonate occurs in the dialysate circuit, the supply of calcium and potassium is easily adapted to individual patients' needs by change in the composition of the reinfusion solution, and a calcium-free dialysate that facilitates citrate anticoagulation is used.

Substitution of Acetic Acid for Hydrochloric Acid in the BicarbonateBuffered Dialysate

In a multicenter study including 5 dialysis units, blood acetate changes during 4 h dialysis sessions in 141 patients treated with a 4 mM acetate-containing bicarbonate dialysate (ABD) were evaluated and compared to the values of 114 patients using an acetate-free bicarbonate dialysate (AFD). Acetate-free bicarbonate dialysate was delivered by a dialysis machine from the mixing with water for dialysis of a 1/26.2 bicarbonate concentrate, and a 1/35 acid-concentrate in which acetic acid was substituted for hydrochloric acid (Soludia, Fourquevaux, France). This new type of dialysate was routinely in use for 3 years on average (range, from 2 to 5 years). All patients fasted before and during dialysis. Blood samples were withdrawn at the start and at the end of dialysis sessions. The acetate plasma concentration was determined using the acetyl-CoA synthetase enzymatic method (Boehringer, Manheim, Germany). In patients treated with ABD whose predialysis blood acetate levels were in the physiologic range of < or = 100 microM (n = 113), the acetate plasma concentration increased from a predialysis mean value of 22+/-3 microM to a postdialysis mean value of 222+/-11 microM in 88 patients (78% of patients) whereas the acetate plasma concentration changes remained in the range of physiologic values from 21+/-6 to 58+/-7 microM in the other 25 patients. In contrast, patients treated with AFD whose predialysis blood acetate levels were in the physiologic range (n = 108), acetate plasma concentration increased from a predialysis mean value of 49+/-6 microM to 160+/-19 microM in only 13 patients (12% of patients) whereas acetate plasma concentration changes remained in the range of physiologic values of 23+/-2 to 41+/-3 microM in most of the patients of this group. In this study, a significant number of patients, whether receiving standard or acetate-free bicarbonate dialysates, exhibited an extremely high acetate plasma concentration at the start of the dialysis session. Hyperacetatemia was controlled with AFD in patients whose predialysis acetate plasma concentration of 316+/-82 decreased to 55 +/-23 microM (n = 6) at the end of the dialysis session whereas the acetate plasma concentration remained high when the predialysis concentration was 580+/-76 microM, with a postdialysis concentration of 233+/-39 microM (n = 28). It is concluded that in patients whose predialysis blood acetate levels were in the physiologic range, acetate-containing bicarbonate dialysate induces hyperacetatemia whereas postdialysis blood acetate remains in the normal range in such dialysis patients treated with acetate-free dialysate. Chronic hyperacetatemia, which could be found in dialysis patients, is well controlled by dialysis using an acetate-free dialysate.

Acetate intolerance is mediated by enhanced synthesis of nitric oxide by endothelial cells.

The clinical picture of acetate intolerance strictly mimics the nitric oxide (NO) effect, including smooth muscle relaxation and extreme vasodilation. Because acetate induces production of cAMP, which is a powerful stimulus of NO synthase (NOS), we evaluated the effect of different dialysate solutions with and without acetate on NOS activity in endothelial cells (EC). NOS activity of EC, evaluated as H3-citrulline produced from H3-arginine, was modulated by the dialysate composition (e.g., 38 mmol/L acetate produced an increase of 3.2 +/- 0.39-fold compared with basal values (P < 0.0005), and the small amount of acetate (4 mmol/L) in 35 mmol/L bicarbonate solution increased the NOS activity by 2 +/- 0.49-fold (P < 0.05). Conversely, the acetate-free solution produced no effect on NOS activity. The mRNA encoding for inducible NOS was highly expressed in EC incubated with acetate buffer and also with acetate in bicarbonate dialysis buffer. The EC proliferative index was depressed by acetate (P < 0.0005), and tumor necrosis factor synthesis was increased (P < 0.0005) compared with acetate-free buffer. This study suggests that dialytic "acetate intolerance" can be induced by the activation, through cAMP and tumor necrosis factor release, of NOS. The small amount of acetate in bicarbonate dialysate, although capable of inducing in vitro NOS activation, is likely to be rapidly metabolized, whereas the large amounts of this anion in acetate fluids overwhelm metabolism by the liver. Acetate-free dialysate is the only solution that provides an acceptable level of biocompatibility both in vivo and in vitro.

Phosphorus Removal With a Variable Chloride, CO2 Acidified Dialysate Using an Unmodified Single Pass System

A method of providing dialysate was developed that used CO2 gas, rather than acetic acid, as an acidifying agent, allowing for the delivery of a variable chloride concentration. The system can be used on a standard, unmodified dialysis machine. The aim of the study was to test the technical feasibility of the dialysate delivery system and to determine whether use of the dialysate, which is free of acetate and can increase serum chloride concentrations above those normally achieved during the early phases of dialysis, could influence mass phosphorus removal. Using a crossover design, the effects of a standard acetate containing dialysate were compared with the acetate free, variable chloride dialysate on serum phosphorus kinetics and mass phosphorus removal in six hemodialysis patients. Although, as predicted, the serum chloride levels were higher during the initial phases of dialysis and serum bicarbonate concentrations were equivalent at the end of treatment, it was not possible to measure any differences in serum phosphorus levels during any of the time points during or immediately after dialysis, nor was any difference in mass phosphorus removal observed. Despite the presence of considerable animal evidence that acetate metabolism causes the intracellular shift of phosphorus, our study did not show any benefit, in terms of mass phosphorus removal, of an acetate free dialysate solution.