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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2017  |  Volume : 28  |  Issue : 3  |  Page : 558-565
Comparison of intradialytic hemodynamic tolerance between on-line hemodiafiltration and acetate-free biofiltration with profiled potassium dialysate concentration

Metabolic Pole and Hemodialysis Unit, Jacques Lacarin General Hospital, Vichy, France

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Date of Web Publication18-May-2017


Intradialytic hypotensive episodes are deleterious for hemodialysis (HD) patients. Acetate-free biofiltration with profiled potassium (AFBK) dialysate concentration may improve their cardiovascular stability. The aim of the present crossover study was to compare intradialytic hemodynamic tolerance and biological parameters between online hemodiafiltration (olHDF) and AFBK. Ten frail HD patients (8 males) with a mean age of 66.71- ± 12.31 years were studied for three months on olHDF and AFBK. There was a significant reduction of the hypotensive episodes during the AFBK period compared to the olHDF period. Mean intradialytic systolic and diastolic blood pressures were significantly higher during the AFBK period. There was a significant postdialytic increase in serum sodium concentration with the AFBK compared to olHDF. The dry weight and ultrafiltration indices were significantly higher, and the Kt/V was significantly lower during the AFBK period. Serum albumin concentration significantly increased during the AFBK period. AFBK leads to a significantly improved intradialytic tolerance in hemodynamically instable HD patients.

How to cite this article:
Kosmadakis G, Correia ED, Somda F, Aguilera D. Comparison of intradialytic hemodynamic tolerance between on-line hemodiafiltration and acetate-free biofiltration with profiled potassium dialysate concentration. Saudi J Kidney Dis Transpl 2017;28:558-65

How to cite this URL:
Kosmadakis G, Correia ED, Somda F, Aguilera D. Comparison of intradialytic hemodynamic tolerance between on-line hemodiafiltration and acetate-free biofiltration with profiled potassium dialysate concentration. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2020 Dec 6];28:558-65. Available from: https://www.sjkdt.org/text.asp?2017/28/3/558/206436

   Introduction Top

Cardiovascular disease is the most common cause of death among dialysis patients, with a 10–20-fold higher mortality rate than in the general population.[1],[2]

Inflammation and oxidative stress have been identified as specific cardiovascular risk factors in dialysis patients and they have been proposed as potential therapeutic targets.[3],[4],[5],[6]

In the context of a dialysis population presenting an increasing mean incident and prevalent age and comorbidity index,[7] the undisputable improvement of the hemodialysis (HD) techniques has not led to significant improvements in the cardiovascular morbidity and mortality.[8] The procedure of HD itself may exert cardiodepressive and pro-inflammatory effects with the intradialytic myocardial stunning being associated with poor dialytic tolerance and hypotensive episodes.[9] Frequent and occasional intradialytic hypotension is related to increased cardiovascular mortality in HD patients.[10]

In the past, the replacement of acetate HD buffer by bicarbonate has led to a significantly improved hemodynamic tolerance with a substantial reduction of intradialytic hypotensive episodes, nausea, vomiting, and headaches.[11]

Nevertheless, in the bicarbonate dialysate, there is still acetate at a usual concentration of 3–4 M. This is up to a 100 times higher than the normal plasma acetate levels. Acetate dialysis is associated with the activation of lipid peroxidation and pro-inflammatory factors that may potentiate a significant hemo- dynamic instability. A substantial increase in plasma acetate may promote hemodynamic instability, inflammation, and acidosis.[12],[13],[14]

The newer HD techniques, like the online hemodiafiltration (olHDF), are based on the infusion of large volumes of real-time fabricated solution produced from the acetate- containing dialysate concentrate. As the effectiveness of the olHDF technique concerning survival and morbidity outcomes is associated with the total volume of the infusion, the final volume of acetate perfused becomes clinically significant.[15],[16]

Acetate-free biofiltration with profiled potassium (AFBK) is a relatively newly presented technique by the Gambro/Baxter® dialysis machines comprising an acetate-free biofil- tration method with a profiling of dialysate potassium concentration. [17]

AFBK method includes a dialysis setting with a complete absence of buffer and a dia- lysate that does not contain acetate, bicarbonate, or potassium in the acid concentrate. Bicarbonate (1.4% sodium bicarbonate solution delivered from specially produced 3 L bags) is infused postdialyzer on a stable re- infusion rate of 2 L/h throughout the dialysis session. The concentrate of potassium chloride is also given on a 4 L bag at a profiled mode.

The potassium concentration of the dialysate is modified during the dialysis in a predefined matter according to the prescription that has been chosen individually for every patient based on his/her known serum potassium dynamics or other contributory factors (digitalis treatment, etc).

The aim of the present crossover study is to investigate the changes in hemodynamic tolerance as well as the clinicobiological parameters of a fragile group of HD patients on olHDF and on AFBK.

   Patients and Methods Top

The anthropometric, dialytic, and hemodyna- mic parameters of 10 selected HD patients (8 males) dialyzed thrice weekly for 4 h/session for 60.86 ± 31.58 months, mean age of 66.71 ± 12.30 years, who presented with serious intradialytic hemodynamic instability (at least 1 hypotensive episode per week on a thrice weekly dialysis schedule), were studied for three months on olHDF and AFBK. Before the switch to the AFBK technique, the patients were dialyzed on conventional HD for a washout period of two weeks. The systolic and diastolic blood pressures were measured and registered at the beginning, the end, and at every 30 min throughout the dialysis session. The measurements were even more frequent in case of hemodynamic instability.

The selected patient group had multiple cardiovascular comorbidities (coronary artery disease in 8/10, cerebral vascular disease in 5/10, peripheral vascular disease in 7/10, and diabetes in 6/10).

All hypotensive episodes were registered during the two dialysis periods. A hypotensive episode was defined as the symptomatic reduction of the arterial pressure necessitating the intervention of the dialysis personnel and the need for dedicated actions such as regulation of ultrafiltration or infusion of 0.9% sodium chloride/blood volume expanders to restore the hemodynamic stability. The hypo- tensive episodes were noted based on the clinical condition and not on the level of the systolic blood pressure itself.

The prescribed medical treatment and dietetic regimen were not changed during the study period.

The volume of reinfusion on postdialyzer olHDF was programmed at 20–25 L/session with a blood pump set at 350–400 mL/min. The dialyzer was a polysulfone Toraysulfone® TS 1.8 m2, with a prescription of a dialysate conductivity at 140 mmol/L, potassium at 2 mmol/L, calcium at 1.5 mmol/L, bicarbonate at 34 mmol/L, and acetate at 3 mmol/L of dialysate.

The standard dialyzer used for the AFBK technique was an Evodial® AN69-Heparan® with a surface of 1.6 m2. Despite the presence of a heparin-coated membrane in this dialyzer, we chose not to change the anticoagulant prescription during the protocol period. On AFBK, the prescribed conductivity was on 140 mmol/L, 1.4% bicarbonate solution was infused postfilter on a rate of 2 L/h, and calcium concentration was 1.5 mmol/L. Potassium was variable depending on the known predialysis serum concentration. On patients with pre- dialytic serum potassium concentration above 5 mmol/L, the dialysate potassium concentration was set at 4 mmol/L at the start with a gradual reduction up to 2 mmol/L at the end of the session. If predialytic serum potassium concentration was 3.5–5 mmol/L, the dialysate potassium concentration was falling gradually from 3 mmol/L at the start to 2 mml/L at the end of the session. If predialytic serum potassium levels were below 3.5 mmol/L, the dialysate potassium concentration was increasing from 2.5 mol/L at the start to 3.5 mml/L at the end of the session. The dialysate temperature for both methods was set at 37°C.

The studied biological parameters were measured before and after dialysis once every month for a period of three months, and the mean values of the three measurements per method were used for the statistical analysis of the two methods. All patients gave their written consent for participating in this study and for the use of data from their personal files and records.

The primary outcome of the present study was the number of hypotensive episodes per dialysis method during the study period. The secondary outcomes were the mean systolic blood pressures before (T0), during (T1, T2, and T3), and after the dialysis sessions (T4) for every technique, the pre- and post-dialytic biochemical parameters, as well as the parameters of dialysis efficiency during the different study periods.

   Statistical Analysis Top

We compared the studied parameters for the two study periods (olHDF and AFBK).

Values are given as mean ± standard deviation (SD). Statistical analysis was performed using the Statistical Package for Social Science (SPSS®) version 21.0 software (SPSS Inc., Chicago, IL, USA). The primary outcome, i.e., the comparison of the total number of hypo- tensive episodes on olHDF versus AFBK was analyzed with the Chi-square test. ANOVA for repeated measurements was performed to test the timing effect of the studied parameters during the study. A paired /-test was used to compare the differences between the studied parameters at the different time intervals throughout the study (olHDF vs. AFBK and pre- vs. post-dialysis). P<0.05 was considered statistically significant.

   Results Top

The baseline individual patients’ characteristics are shown in [Table 1]. The mean clinico- biological values are shown in [Table 2]. There was a significant reduction of the dry weight after the introduction of AFBK. All the ultra- filtration parameters (mean ultrafiltration volume, ultrafiltration as a percentage of the dry weight as well as the ultrafiltration rate) were significantly greater during the AFBK period. In a total of 380 dialysis sessions per method, 153 clinically significant hypotensive episodes were noted during the olHDF period and only 10 on the three months of the AFBK technique (P = 0.019).
Table 1: Individual characteristics of the studied patients.

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Table 2: Clinicobiological parameters of the studied periods.

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The mean systolic and diastolic arterial pressures were measured predialysis (T0) during dialysis (T1, T2, and T3), and at the end of the dialysis session (T4) for all the patients and all the dialysis sessions per dialysis method. The mean systolic arterial pressure was not significantly different at the start (T0) of the dialysis session whereas diastolic blood pressure was significantly higher during the AFBK period at T0 [Table 2]. The systolic blood pressure values on the 1st (T1), 2nd (T2), 3rd (T3) h, and at the end of the 4 h HD session (T4) were significantly higher during the AFBK period [Figure 1].
Figure 1: Mean systolic blood pressure throughout the dialysis session.
T0: Predialytic systolic blood pressure, T1, T2, T3: Intradialytic systolic blood pressure, T4: Postdialytic systolic blood pressure.

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In what concerns the biological parameters [Table 2], there was no significant difference between the methods concerning the predia- lysis serum sodium and phosphate as well as the pre- and post-dialysis serum potassium. Urea reduction ratio and Kt/V were significantly reduced during the AFBK period, but the mean value was within the recommended limits. Serum albumin was significantly increased during the AFBK period.

During the olHDF period, the serum sodium levels did not change significantly during dialysis on the monthly pre- and post-dialytic blood test (P non-significant), whereas there was a significant postdialytic increase of serum sodium levels during the AFBK period (P <0.001). There were no statistically significant differences between the two methods concerning the predialysis sodium concentration whereas the postdialysis levels were significantly different (P = 0.034). All the pre- and post-dialytic serum sodium concentrations were stable during the three months of the study.

   Discussion Top

The present study compared the effects of olHDF and AFBK on a selected frail group of HD patients who present frequent hypotensive episodes.

A significant reduction in the frequency of the hypotensive episodes was observed on AFBK. This has also been noted in other studies with the acetate-free biofiltration (AFB) technique without potassium profiling and lately in a study with the more recently introduced AFBK method, but the differences were not as important as in the present study.[18],[19],[20],[21]

In a trial by Cavalcanti et al on a frail group of HD patients, AFB was associated with a significant reduction of hypotensive episodes compared to conventional HD.[22]

The significant improvement of the intradia- lytic hemodynamic tolerance may be attributed to:

  1. The absence of acetate from the dialysate that exerts important vasodilatatory properties through NO-associated mechanisms. In a study by Noris et al, dialysis with acetate led to a significant reduction of intradialytic systolic blood pressure with a consistency between the release of excessive amounts of NO coupled with vaso- dilatory cytokines and an important hemo- dynamic instability.[12] In an in vitro study performed on ventricular cardiac myocytes that were treated on different dialysis baths, the presence of acetate on the dialysis bicarbonate solution was found to affect the expression of NO-synthetase and the duration of the myocytes’ action potential that might be associated with the cardiac contractile impairment in hemo- dynamically unstable patients[23]
  2. The cooler bicarbonate and potassium concentrates infused from bags after the dialyzer, even though the solution was heated before the reinfusion. In a study by Kumar et al the authors were unable to demonstrate any advantage for HDF over conventional HD using cooled dialysate in terms of changes in blood pressure during a treatment session, or differences in the relative changes in intra- or extra-cellular volumes[24]
  3. The significant increase in postdialytic sodium concentration that has also been seen in other similar studies[25] originating from the bicarbonate sodium bags infused postdialyzer
  4. The gradual and more physiological reduction of serum potassium concentration with the profiled potassium dialy- sate concentration[21]
  5. The improved cardiac tolerability associated with a lower intradialytic arrhythmo- genic potential observed in the profiled potassium dialysate studies. In a study by Santoro et al, there was a clear association between the mode and rhythm of potassium extraction and the intradialytic arrhythmogenic potential[25]
  6. The different peripheral resistance adaptation and changes in the cardiac stroke volume and contractility. Cavalcanti et al in their above-mentioned study performed a model-based computer analysis of the dialysis sessions and concluded that intra- dialytic stroke volume reduction was less important on AFB compared to bicarbonate dialysis whereas peripheral resistance adaptation was significantly higher on bicarbonate dialysis. In that context, hypotension occurred later in AFB. That implies a better conservation of the reflex compensatory responses to hypovolemia on AFB compared to conventional HD.[22]

The increased ultrafiltration per dialysis session along with the improvement of the serum albumin levels despite the slight reduction in the dry weight may be due to the improved patients’ nutrition in view of an improved hemodynamic tolerance. These are factors associated with significantly improved outcomes.[26]

The reduction of the Kt/V can be explained by the reduction of the total volume of reinfu- sion as in the postfilter olHDF technique. The volume varied between 20 and 25 L/session, whereas in the AFBK technique, the total was about 8–9 L from the bicarbonate solution and 3 L from the reinfused potassium concentrate. The dialyzer used in the AFBK technique had also a smaller surface (1.6 m2) than the one on olHDF (1.8 m2).

The introduction of newer procedures and dialysis modules (e.g., biofeedback controlled, cooled dialysis, or online hemofiltration and hemodiafiltration) has led to an improvement of the hemodynamic tolerability of dialysis sessions and a reduction of the intradialytic hypotensive episodes that is not as significant as the one observed under AFBK.[27],[28],[29],[30]

We are aware that our study has several drawbacks. For a start, it was not blinded, since this would have been impossible in a clinical setting given the use of infusate bags for AFBK but not for olHDF and the use of different models of dialysis machines for the two techniques. Second, it was not randomized as there was a deliberate selection of a small group of frail dialysis patients with frequent intradialytic hypotensive episodes studied on a crossover manner with a washout period in between.

In conclusion, the introduction of the AFBK technique has led to a significant improvement of the intradialytic hemodynamic tolerance and the general clinical condition of a group of frail patients presenting frequent intradialytic hypotensive episodes under high-volume olHDF. Certain clinical and biological parameters were also changed after the intro- duction of the AFBK. A postdialytic increase in serum sodium levels associated with the sodium bicarbonate infusion has also been observed which necessitates an overall reduction of dialysate osmolality.

Larger studies are needed to explain this improved hemodynamic tolerance. Cardiovascular outcomes could also be studied with bigger randomized trials to study a potential association of a better cardiovascular intra- dialytic tolerability with cardiovascular morbidity and mortality.

Conflicts of interest: None declared.

   References Top

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Del Vecchio L, Locatelli F, Carini M. What we know about oxidative stress in patients with chronic kidney disease on dialysis - Clinical effects, potential treatment, and prevention. Semin Dial 2011;24:56-64.  Back to cited text no. 3
Tsirpanlis G. Is inflammation the link between atherosclerosis and vascular calcification in chronic kidney disease? Blood Purif 2007;25: 179-82.  Back to cited text no. 4
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Noris M, Todeschini M, Casiraghi F, et al. Effect of acetate, bicarbonate dialysis, and acetate-free biofiltration on nitric oxide synthesis: Implications for dialysis hypotension. Am J Kidney Dis 1998;32:115-24.  Back to cited text no. 12
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Correspondence Address:
George Kosmadakis
Metabolic Pole and Hemodialysis Unit, Jacques Lacarin General Hospital, Vichy
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DOI: 10.4103/1319-2442.206436

PMID: 28540893

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