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

Autores de IIS La Fe

• María Roca Llorens

  Autor

• Luis Carlos López Romero

  Autor

• Aina Gomez Bori

  Autor

• Ramon Devesa Such

  Autor

• Amparo Soldevila Orient

  Autor

• Pilar Sanchez Perez

  Autor

• Julio Hernández Jaras

  Autor

Participantes ajenos a IIS La Fe

• Broseta J.J.
• Rodríguez-Espinosa D.
• Cuadrado-Payán E.
• Bea-Granell S.

Grupos

• Enfermedad celíaca e Inmunopatología digestiva

• Farmacogenética

• Unidad Mixta de Investigación en Nanomedicina y Sensores

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. © 2022 by the authors.

Keywords

• Acetates; Acetylcarnitine; Bicarbonates; Citrates; Citric Acid; Citric Acid Cycle; Dialysis Solutions; Glutamates; Glutarates; Glycerol; Humans; Inositol; Ketone Bodies; Lactates; Prospective Studies; Pyruvic Acid; Renal Dialysis; Salts; Triglycerides; 2 oxoglutaric acid; 3 hydroxybutyric acid; acetic acid; acetoacetic acid; acetylcarnitine; amino acid; citric acid; fumaric acid; glutamic acid; glutaric acid; glycerol; inositol; isocitric acid; ketone body; lactic acid; malic acid; pyruvic acid; succinic acid; triacylglycerol; acetic acid; bicarbonate; citric acid; dialysis fluid; glutamic acid derivative; inorganic salt; adult; anaerobic metabolism; Article; citric acid cycle; clinical article; controlled study; degradation; female; glycolysis; hemodialysis; human; ketogenesis; male; metabolism; metabolomics; middle aged; prospective study; adverse event