Has time come to replace the residual acetate with citrate in the dialysis fluid?

Abstract

Journal of Nephrology is publishing in this issue the results of a randomized clinical study comparing citrate and acetate as pH stabilizer in high-volume online haemodiafiltration (HDF) on interleukin-6 (IL-6) and Klotho levels [1]. Acetate has been used in the haemodialysis (HD) dialysate since the 1960s, initially as the sole buffer at high concentrations (30–40 mMol/L). High concentrations, up to 40 mMol/L, result in bicarbonate generation after liver metabolization. At such concentrations acetate is a potent vasodilator and myocardial depressor and can cause intradialytic hypotension [2]. Acetate-based dialysate has been soon associated with other significant side effects, such as nausea and increased inflammatory response [1]. Consequently, in the 1980s bicarbonate-based dialysate progressively replaced acetate-based dialysate, even if the former still contains relatively low amounts of acetate (3–5 mMol/L) to stabilize the pH and prevent calcium precipitation. These levels are still far from physiological, raising concerns especially for the older and more vulnerable dialysis patients with low muscle mass, and therefore at higher risk for acetate intolerance [1]. As pre-dialysis blood levels of acetate are usually lower than 0.1 mMol/L, during treatment the dialysate to blood gradient causes a positive acetate mass balance and a 5–6 fold increase of acetate plasma levels [3]. Acetate mass-transfer has been estimated to be about 72 mMol, that is about 36% of the full buffer gain [3]. By using convective therapies as demonstrated by Fournier et al. [4], acetate mass transfer increases significantly with greater post-dialysis blood acetate levels in patients treated with online HDF compared to bicarbonate HD. Thus, it is conceivable that the residual acetate in the bicarbonate-based dialysate may cause significant side effects to the patient.