Buffer Therapy in Acute Metabolic Acidosis: Effects on Acid-Base Status and Glomerular Permeability

ABSTRACT Background: Correction of acute metabolic acidosis using sodium bicarbonate is effective, but has been hypothesized to exacerbate intra-cellular acidosis causing cellular dysfunction. The effects of acidemia and bicarbonate therapy on the cellular components of the glomerular filtration barrier, crucial for the integrity of the renal filter, are as yet unknown. Controversy persists regarding the most appropriate method to assess acid-base status: the “Stewart approach” or the “Siggaard-Andersen approach” using the standard base excess (SBE). Methods: Here we performed physiological studies in anesthetized Sprague-Dawley rats during severe metabolic acidosis (HCl iv 6 mmol kg -1 ) and following bicarbonate (2.5 mmol kg -1 ) administration. We assessed glomerular permeability using sieving coefficients of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400. Acid-base status was evaluated using SBE, standard bicarbonate, total CO 2 , the Stewart-Fencl strong ion difference (ΔSID = Na – Cl – 38) and a theoretical model of plasma and erythrocyte strong ion difference. Results: Our data show that neither acidosis nor its correction with NaHCO 3 altered glomerular permeability. We identified ΔSID as a strong estimator of plasma base excess (as assessed using the Van Slyke equation). In silico modeling indicates that changes in the strong ion difference in erythrocytes would explain their buffering effect by means of a shift of anions from the extracellular fluid. Conclusion: These data demonstrate a remarkable tolerance of the glomerular filter to severe acute acidosis and bicarbonate therapy. Our results also cast light on the buffer mechanism in erythrocytes and the ability of different acid-base parameters to evaluate the extent of an acid-base disorder. IMPORTANCE STATEMENT Metabolic acidosis is a frequent complication of acute kidney injury in critically ill patients and is associated with a high risk of mortality. Correction of acidosis using sodium bicarbonate is simple and effective, but could possibly induce intracellular acidosis causing cellular dysfunction. The effects of acidemia and subsequent bicarbonate treatment on the cellular components of the glomerular filtration barrier, crucial for the integrity of the renal filter, are unknown. We show that neither severe acidemia nor bicarbonate therapy appear to have negative effects on glomerular permeability. Our analysis also highlights the buffering effects of erythrocytes, which appear to be mediated by a shift of strong anions into the red cells, increasing the strong ion difference in the extracellular fluid.