An Alternate Base for Hemodialysis: The Promise of l‐Lactate

Abstract

Acetate dialysis solution, especially when used in a high-efficiency dialysis setting, has been associated with hypotension and with symptoms such as nausea, vomiting, and fatigue (1, 2). At present, bicarbonate is the dialysis solution base of choice in highefficiency dialysis. Bicarbonate, however, has prob lems as well, such as the requirement for a relatively complex dual concentrate delivery system adding to the cost of dialysis. In addition, the danger of bacterial contamination exists with bicarbonate concentrate solutions (3, 4).The thinking of the dialysis community with regard to potential bases has been largely bipolar: the choice is either acetate or bicarbonate. However, it has long been recognized that bicarbonate-generating compounds other than acetate are available. Liang and Lowenstein ( 5 ) found that the infusion of pyruvate into dogs was associated with less cardiovascular effects than that of acetate. Wathen et al. (6) demonstrated the bicarbonate-generating ability of pyruvate and m-lactate infused into anesthetized dogs while Gonzalez et al. (7) made similar observations with intravenous succinate.During the past several years, our group has focused on the possibility of using lactate as a dialysis solution base. Our interest in lactate began with studies of the vasorelaxant effects of various potential bicarbonate-generating bases in isolated vascular tissue. In the rat caudal artery, we found that lactate caused far less vasorelaxation than acetate (8). In other studies, we confirmed that acetate has potent vasodilator (9, 10) and cardiodepressant effects (1 1) at concentrations commonly achieved during dialysis. In conscious dogs, acetate, when used in a dialysis setting, and with plasma acetate levels of only 2 to 3 mM, was associated with a substantial decrease in total peripheral resistance. In fact, in sympathectomized dogs, acetate dialysis, but not ' bicarbonate dialysis, was associated with transient cardiovascular collapse (12). All of these findings suggest that use of alternative agents to acetate may be beneficial.We began feasibility studies in patients using DLlactate as a dialysis solution base. We found that a dialysis solution containing 40 mM DL-lactate resulted in insufficient correction of acidosis ( 13, 14). A reduction in symptoms with lactate was not found in these studies, probably because the control acetate treatments were virtually asymptomatic, as only regular, "low-efficiency" dialysis was examined. We then became concerned about reports that exposure to Dlactate might have adverse neurological consequences (15,16). About the same time, chemical firms began to market biologically derived L-lactate for the same price as DL-lactate. We subsequently did a follow-up study comparing DL-Iactate (20 mM of each isomer) with L-lactate (40 mM) as the sole dialysis solution base. No clinical differences were observed and correction of acidosis was comparable though suboptimal, with both forms of lactate. These data suggested that a lactate concentration higher than 40 mM...