Impact of Acetate versus Citrate Dialysates on Intermediary Metabolism—A Targeted Metabolomics Approach

Abstract

Acetate is widely used as a dialysate buffer to avoid the precipitation of bicarbonate salts. However, even at low concentrations that wouldn’t surpass the metabolic capacity of the Krebs tricarboxylic acid (TCA) cycle, other metabolic routes are activated, leading to undesirable clinical consequences by poorly understood mechanisms. This study aims to add information that could biologically explain the clinical improvements found in patients using citrate dialysate. A unicentric, cross-over, prospective targeted metabolomics study was designed to analyze the differences between two dialysates, one containing 4 mmol/L of acetate (AD) and the other 1 mmol/L of citrate (CD). Fifteen metabolites were studied to investigate changes induced in the TCA cycle, glycolysis, anaerobic metabolism, ketone bodies, and triglyceride and aminoacidic metabolism. Twenty-one patients completed the study. Citrate increased during the dialysis sessions when CD was used, without surpassing normal values. Other differences found in the next TCA cycle steps showed an increased substrate accumulation when using AD. While lactate decreased, pyruvate remained stable, and ketogenesis was boosted during dialysis. Acetylcarnitine and myo-inositol were reduced during dialysis, while glycerol remained constant. Lastly, glutamate and glutarate decreased due to the inhibition of amino acidic degradation. This study raises new hypotheses that need further investigation to understand better the biochemical processes that dialysis and the different dialysate buffers induce in the patient’s metabolism.

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“…Acetate also activates nitric oxide which causes vasodilatation [ 4 ]. The clinical manifestation of the BAA is an arterial pressure decrease and a heart rate increase [ 5 ]. Their study has shown that certain categories of patients with AKI after CS have lower rates of acetate metabolism [ 2 ].…”

“…Replacing acetate by hydrochloric acid in SBD is a promising alternative; however, it is only done in a minority of cases [ 2 ]. Acetate is widely used as a weak acid acting as a dialysate buffer, thus avoiding this precipitation [ 5 ]. Even at the low concentrations (3–4 mmol/L) used, it reaches blood levels higher than physiological [ 5 ], leading to undesirable outcomes by poorly understood mechanisms [ 5 ].…”