Acid-Free Biocompatible Hemodiafiltration

In bicarbonate dialysis (BD), 2–4 mmol/L of acetic acid are added to dialysate to maintain salts in their soluble form. After giving up the hydrogen ion, the acetate anion diffuses into the bloodstream, increasing blood acetate concentration up to 0.3 mmol/L [1]. In acetate-dialysis, acetate concentration was much higher, ranging between 4 mmol/L and 10 mmol/L, and 1 out of 11 patients was unable to metabolize such acetate overload so experiencing “acetate intolerance” which included vascular instability with intradialytic hypotension (IH). Although the mechanisms of acetate-related hypotension are varied, the different rates at which patients metabolize acetate load from dialysate account for the higher blood acetate levels in intolerant patients, which in turn cause vascular instability. However, given the magnitude of such figures, it seems unlikely that this can happen also during BD. In fact, when dialyzed against bicarbonate dialysate containing 8 mmol/L acetate, no symptom arises, specifically hypotension does not occur [2].

Acetate-free biofiltration (AFB) was claimed to reduce IH with respect to BD [3] and to on-line hemodiafiltration (HDF) [4]. If, at current concentrations, acetate is not responsible for hemodynamic instability and IH, then the absence of acetate in AFB cannot justify the improved hemodynamic tolerance of the technique. As a distinctive characteristic AFB has carbon dioxide (CO₂)-free dialysate which avoids the CO₂ overload that instead occurs in BD [5] and HDF [6]. This unique feature is due to the lack of acid in the dialysate because is just the acid that generates CO₂ by reacting with bicarbonate.

Acetic acid is commonly used in BD and HDF, but by replacing it with citric acid or hydrochloride acid, the same reaction occurs, still leading to CO₂ overload. Citrate-based treatments, despite being acetate-free, show increased partial pressure of CO₂ in blood exiting the extracorporeal circuit and are associated with hemodynamic instability [7]. Cardiac output and peripheral vascular resistance do not change by replacing acetic with citric acid [8], but a significant decrease in IH incidence occurs if acid is removed by dialysate: patients receiving HDF with acetate-free chloride-based dialysate improved their hemodynamic stability during 3-month period of AFB [9]. Taken all together, these evidence suggest that hemodynamic tolerance is not related to acetate anion but to the lack of acid, regardless of what it is.

The lack of acid and the CO₂-free dialysate make AFB a suitable technique for patients unable to handle CO₂ overload but also for patients at risk of IH. The new insights in pathophysiology of AFB depict the technique very differently than we knew. To underline this novelty, it is not enough to replace the term “acetate” with “acid,” as I already suggested [10]. Here, I would propose to use the new label “acid-free biocompatible hemodiafiltration.” The term biocompatible should not be intended as behavior of the filter membrane but as the ability of dialysis technique to be in contact with a living system with fewer adverse effects. Being a convective-diffusive treatment, the word “hemodiafiltration” is also appropriate.