|Year : 2008 | Volume
| Issue : 2 | Page : 215-221
|Variability of Acid-Base Status in Acetate-Free Biofiltration 84% versus Bicarbonate Dialysis
Kais Harzallah, Nourredine Hichri, Chakib Mazigh, Mohamed Tagorti, Ahmed Hmida, Jalel Hmida
Unity of Organ Transplantation, Unity of Hemodialysis, Military Hospital of Tunis, Tunisia
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| Abstract|| |
The ultimate goal of hemodialysis (HD) treatment is to achieve the highest level of efficacy in the presence of maximal clinical tolerance. With an aim to offer good hemodynamic stability, as observed during the acetate-free biofiltration 14% (AFB 14%) to patients who are intolerant to bicarbonate dialysis (BD) and with less cost, we have developed since June 1994, a new HD technique, namely AFB 84%. This study was carried out to analyze acid-base variations during the AFB 84% in comparison to BD in hemodynamically stable patients on regular HD. This was a prospective randomized crossover study carried out on 12 patients (6 males and 6 females) for a total of 144 HD sessions (72 BD and 72 AFB 84%). Patients with decompensated cardiomyopathy, respiratory diseases or uncontrolled hypertension were not included in the trial. All the patients were treated with BD or AFB 84%; the latter is characterized by the absence of acetate in the dialysate and a complete correction of buffer balance by post-dilutional infusion of bicarbonate-based replacement solution. The comparison of pre-dialysis arterial acid-base and blood-gas parameters revealed no significant differences of pH, HCO 3 - and paCO 2 levels between the two techniques. Analysis of post-dialysis parameters showed that, among patients dialyzed with BD, there was over correction of metabolic acidosis with a tendency towards metabolic alkalosis. In contrast, in patients dialyzed with AFB 84%, we observed a significant improvement in pH and HCO 3 - levels but the increase in paCO2 level was not significant. A comparison of these parameters between the two techniques showed statistically significant difference in pH, HCO3 - and paCO2 levels, but not for paO2 level. AFB 84% can offer some important advantages with the complete absence of acetate from the substitution fluids, and permits a better correction of metabolic acidosis than BD, without causing alkalosis.
|How to cite this article:|
Harzallah K, Hichri N, Mazigh C, Tagorti M, Hmida A, Hmida J. Variability of Acid-Base Status in Acetate-Free Biofiltration 84% versus Bicarbonate Dialysis. Saudi J Kidney Dis Transpl 2008;19:215-21
|How to cite this URL:|
Harzallah K, Hichri N, Mazigh C, Tagorti M, Hmida A, Hmida J. Variability of Acid-Base Status in Acetate-Free Biofiltration 84% versus Bicarbonate Dialysis. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2020 Aug 13];19:215-21. Available from: http://www.sjkdt.org/text.asp?2008/19/2/215/39033
| Introduction|| |
The ultimate goal of hemodialysis (HD) treatment is to achieve the highest level of efficacy in the presence of maximal clinical tolerance. In recent years, bicarbonate has been increasingly used as the main buffer. However, acetate has not been completely abandoned. Acetate (3-4 mmol/L) is still added to substitution fluids containing electrolytes and bicarbonate, in order to prevent calcium salt precipitation. Acetate infusion can induce some untoward clinical effects, including cardiovascular instability and increased nitric oxide synthesis. 
A new technique for renal replacement therapy (RRT), acetate free-biofiltration (AFB), which is a hemodiafiltration technique based on continuous post-dilution infusion of a sterile isotonic bicarbonate solution-14%, aimed at obviating the aforementioned problem, was proposed about 20 years ago. ,, However, due to the high costs on the one hand and the limited financial resources on the other, AFB 14% is still restricted to a small dialysis population. 
Aiming to offer to patients intolerant to bicarbonate dialysis (BD) the same hemodynamic stability observed during the AFB 14% and with a less cost, the dialysis team of the military hospital of Tunis has developed since June 1994, a new HD technique and titled it AFB 84%.  This technique was earlier proved useful in patients with poor hemodynamic tolerance to BD. ,
The aim of our study is to analyze acidbase variations during the AFB 84% and compare the results with stable hemodynamic patients on periodic HD.
| Subjects and Methods|| |
This was a prospective randomized crossover study carried out on 12 patients (6 males and 6 females) for a total of 144 HD sessions (72 BD and 72 AFB 84%).
The study patients were on HD for more than six months at the beginning of the study, and all had a well functioning internal arteriovenous fistula. Their age was between 26 and 76 years.
Patients with decompensated cardiomyopathy, intractable respiratory diseases or those with uncontrolled hypertension were not included in the study. All the study patients were treated with BD and AFB 84% characterized by the absence of acetate in the dialysate and a complete correction of buffer balance by post-dilutional infusion of bicarbonate-based replacement solution. 
For both techniques, dialysis sessions were carried with polysulfone or triacetate low permeability membranes. For conventional BD, the dialysate contained 143-146 mEq/L of sodium; 33-35 mEq/L of bicarbonate, 1.5 mmol/L of calcium and 2.1-2.2 mmol/L of potassium. The dialysate also contained 5-6 mEq/L of acetate.
AFB 84% was carried out with triacetate low permeability membrane for all the patients. It was carried out with liquid substitution (hypertonic sodium bicarbonate 84%) at a rate of 4-4.5 ml/kg/hour (volume schedule 250-300 ml/hr with a maximum of 1500 ml per dialysis session). The dialysate contained 121-124 mEq/L of sodium.
All other dialysis parameters such as blood flow (250-300 ml/min), dialysate flow (500 ml/min) and dialysis duration (240-360 min) were similar for both treatments. For both techniques, we used an automatic ultrafiltration control system (Hemoscan®) and a manual adjustment of ultrafiltration rate if required, throughout the session. Each patient was studied for four weeks. Each treatment schedule was carried out for two weeks (6 sessions) and the BD-AFB or ABF-BD was randomized in each patient.
A detailed monitoring of patients' symptoms was carried out by recording the number of inter-dialytic symptoms (anorexia, vomiting, hiccup, headache, thirst, cramps, effort and rest dyspnea) as well as symptoms occurring during each session (hypertensive crises, vomiting, cramps, headache).
Hypotensive episodes defined as systolic pressure below 95 mm Hg combined with clinical symptoms requiring drug administration were also registered. The patients were also required to score their degree of subjective well-being on a monthly basis; poor (0), fair (1), good (2), very good (3).
Clinical and biochemical tests
The following data were collected:
- The body weight before and after each dialysis session.
- Arterial pressure and heart rate every 30 minutes during the dialysis session.
- Blood acid-base status measured before and after each dialysis session.
- Blood electrolytes before dialysis, at two hours of dialysis and at the end of dialysis (4 hours).
- Phosphate and calcium before and after the fourth dialysis session
- Haptoglobin before and after dialysis session during the first and the sixth dialysis sessions
Data are expressed as mean ± standard deviation (SD). Correlations between values of pH, paCO 2 , paO 2 and HCO 3 levels were performed with Pearson's correlation coefficients. P < 0.01 was considered statistically very significant and p < 0.05 was considered statistically significant.
| Results|| |
The comparison of pre-dialysis arterial acid-base and blood-gas parameters between the two techniques revealed no significant differences (non paired t-test) of pH, HCO 3 and paCO 2 levels.
Analysis of post-dialysis parameters in patients dialyzed with BD revealed over correction of metabolic acidosis with a tendency towards metabolic alkalosis. We observed a higher pH level and higher levels of paCO 2 and HCO 3 in these patients (p < 0.001) [Table - 1].
In contrast, in patients dialyzed with AFB 84%, we observed a significant increase in pH and HCO 3 levels (p< 0.001) but without metabolic alkalosis. The increase in paCO 2 level was not significant in contrast to the decline of paO 2 level (p < 0.001) [Table - 1].
A comparison of these parameters between the two techniques showed statistically significant difference in pH (p < 0.001), HCO 3 level (p < 0.001) and paCO 2 level (p < 0.05) but not for paO 2 level [Table - 1].
The serum sodium concentration remained stable during the entire dialysis session among patients on BD. Among patients on AFB 84%, the increase in sodium level was principally during the first two hours of dialysis but remained stable subsequently. The variation of pre-dialysis sodium was significantly higher in patients on AFB 84% than those on BD [Table - 2].
No significant differences were found between the two techniques in the serum potassium concentration. However, a decline in serum potassium was observed during the first two hours of dialysis [Table - 2].
At the end of AFB 84% dialysis session, the serum chloride concentration showed a significant increase in comparison to BD (112.8 ± 4.11 vs 105.2 ± 5.36) [Table - 2]. During AFB 84%, the serum chloride decreased during the inter-dialysis period although the pre-dialysis values were persistently elevated (107.2 ± 5.68 vs 104.5 ± 4.94). The serum calcium, phosphorus and haptoglobin concentrations remained the same during both the techniques. Despite a substitution volume of 1000-1500 ml of bicarbonate during AFB 84%, we did not observe any significant difference in the inter-dialysis weight between the two techniques [Table - 3].
There was no significant difference between the two techniques in the frequency of complications. However, all the patients declared having better well-being with less thirst with BD and, less tiredness with AFB 84% [Table - 3]. The difference was not statistically significant.
| Discussion|| |
Metabolic acidosis is one of the main abnormalities observed in the dialysis patient and its correction is an important objective. Indeed, the acidosis has several deleterious effects such as increasing the turn-over of muscle protein, enhancing the protein-caloric malnutrition, depressing the myocardial contractility and the vasomotor tone as well as stimulating bone resorption. 
To correct the metabolic acidosis, it is necessary to deliver, during every dialysis session, a quantity of bicarbonate to neutralize the hydrogen ions present in excess in the patient. During BD, bicarbonate buffer comes from the dialysate, which usually contains 35 mEq/L of bicarbonate and 4-10 mEq/L of acetate. Acetate causes vasodilatation by activation of tissue nitric oxide and has an inhibitory effect on cardiac contractility and heart rate.  Also, in vitro studies have shown that acetate causes enhanced iNOS transcription due to increased cytokine and cAMP production.  Todeschini et al have reported that AFB 84%, unlike BD, does not cause activation of polymorphonuclear neutrophils or monocytes. 
To avoid acetate, Van Stone and Mitchell reported for the first time in 1980, the use of a dialysis technique using a dialysate bath completely devoid of any bases. The correction of acid-base abnormalities was by infusion of small amounts of hypertonic sodium bicarbonate using the post-dilution method. Subsequently, Bene et al  and Zucchelli et al  have developed the concept of biofiltration with a complete elimination of usage of acetate.
Clearly, AFB 14% improves intra and interdialysis symptoms as well as patient wellbeing. Verzetti et al  reported that AFB reduced intra and inter-dialysis symptoms by 39 and 28% respectively and the number of hypotensive episodes was reduced by 44%. In AFB 14%, correction of acidosis is achieved by intravenous infusion of 145 mEq/L of bicarbonate in a quantity six to nine liters, while in AFB 84%, we administered bicarbonate at a rate of 250 to 300 ml/h which amounted to 1 to 1.5 liters per dialysis session.
Typically, plasma bicarbonate concentration rises by 4-5 mEq/L during dialysis, but returns gradually to pre-dialysis levels over the ensuing 48 hours.  On completion of a dialysis session with BD, blood pH and plasma bicarbonate increase to approximately 7.5 and 28-32 mEq/L respectively. This mild alkalemia is not long lasting and returns to normal over 48 hours. 
In our study, we observed a significant increase of pH and HCO3 in both techniques at the end of the dialysis session, with a metabolic alkalemia with BD [Table - 1]. This is a positive point for using AFB 84%, because alkalemia can facilitate vascular calcification. 
Mild hypoxemia was seen in our patients with both techniques. Intra-dialysis hypoxemia is well known during HD treatment using acetate-buffered dialysate. It characteristically occurs within the first hour of dialysis when acetate is used as a buffer, and results in a decrease in oxygen tension by about 10 mm Hg. Hypoxemia is less severe and somewhat delayed in onset, if bicarbonate dialysate is utilized. ,
The paCO 2 increased slightly with BD, although it was within the normal range. Studies comparing the effects of bicarbonate and acetate baths in patients using the same dialysis membranes, have shown that CO 2 tension actually rises during dialysis when bicarbonate dialysate is used. However, carbon dioxide clearance is less an issue when bicarbonate bath is used, because it generates its own CO 2 when the bicarbonate bath is mixed with an acid bath to generate dialysate. , In our study, we did not observe any significant increase in paCO 2 tension with AFB 84%.
During AFB 84% as well as 14%,  bicarbonate transfer results from the balance between diffusive and convective bicarbonate losses in the dialyzer and the amount of bicarbonate infused in the venous return. Thus, bicarbonate supply can increase along with the rise in plasma bicarbonate concentration until a steady state is reached, when the rate of infused bicarbonate equals bicarbonate losses into the dialyzer. Because of the large amount of sodium infused and the unusual high chloride concentration in the dialysate, significant difference in the predialysis and the post-dialysis plasma sodium and chloride levels has been observed during AFB 84%. The kinetics of pre-dialysis hypernatremia with a dialysate sodium concentration of 123 ± 2 mmol/L during AFB 84% permits a better distribution of the water volumes, principally in the vascular compartment, and a better cardiovascular function. We did not observe in our study, excessive thirst or inter-dialytic weight compared to BD [Table - 3].
Acetate free biofiltration is a technique based on a buffer-free dialysate with bicarbonate infusion in the post-dilution mode. The absence of bicarbonate or acetate is compensated by chloride ions in the dialysate in order to preserve the electroneutrality of the solution. The concentration of chloride in the dialysate during the AFB 84 is 133.5 mmol/L as against 145 mmol/L in AFB 14% and 105 mmol/L in BD. We did not observe any significant difference in serum chloride levels between AFB 84% and BD during the interdialysis period. It is probably due to the exchange between chloride ions and the bicarbonate coming from the red globules thus reaching the equilibrium of Gibbs Donnan.  Because of the hyperchloremia, Perrone et al  have reported occurrence of hemolysis during AFB 14%. We did not observe this phenomenon during AFB 84% [Table - 2].
For stable patients, a dialysate potassium of 2 mmol/L is considered advisable in order keep pre-hemodialysis plasma potassium below 6 mmol/L. On the other hand, the safety of dialysate potassium concentration is also related to avoidance of hypokalemia and dialysis-induced arrythmias. , In our study, we observed similar potassium clearance in both techniques [Table - 2].
Metabolic acidosis in chronic renal failure is associated with a net negative calcium balance and when metabolic acidosis is corrected, the calcium balance becomes less negative.  In our study, with a dialysate calcium concentration of 1.5 mmol/L, we observed an increase of plasma calcium between the beginning and the end of a dialysis session with AFB 84% (2.32 ± 0.24 mmol/L vs 2.43 ± 0.13 mmol/L). [Table - 2].
Hyperphosphatemia and an increased calcium x phosphate product have been directly linked to increased mortality in a large number of hemodialysis patients.  Phosphate dialysis removal (PDR) depends in part on the type of dialysate (acetate or bicarbonate) and the concentration of the buffer dialysate.  PDR was good in both the techniques with a similar variability of pre-dialysis plasma phosphorus levels (1.05 ± 0.3 mmol/L for AFB 84% and 1.04 ± 0.3 mmol/L for BD) [Table - 2].
In conclusion, our study demonstrates that both BD and AFB 84% share most of the features of optimal renal replacement therapy. AFB 84% can offer some important advantages with the complete absence of acetate from the substitution fluids and, permits a better correction of metabolic acidosis than BD without alkalosis and with less cost.
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Unity of Organ Transplantation, Unity of Hemodialysis, Military Hospital of Tunis, 1008 Tunis
[Table - 1], [Table - 2], [Table - 3]
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