Renal CO2 production from glutamine and lactate as a function of arterial perfusion pressure in dog.

Abstract

The energy cost of renal function in the intact kidney of the dog was assessed at a series of arterial perfusion pressures. Pressure was varied by partially inflating a balloon at the tip of a catheter positioned in the aorta above the origins of the renal arteries. Either L{ U-'4C]glutamine or L-U-14C] lactate was infused intravenously in tracer amounts throughout each experiment. Total renal CO2 production and 14C02 production from each isotope permitted assessment of total renal oxidative metabolism and the proportions derived from the two major substrates of the kidney. Stepwise inflation of the aortic balloon progressively lowered glomerular filtration rate, renal blood inflow, filtered and consequently reabsorbed Na+, total renal CO2 production, and 14CO2 derived from glutamine and lactate. The percent of total CO2 derived from lactate decreased more or less in proportion to the decrease in percent of total CO2 produced. Results were consistent with the view that reabsorption of sodium is the major energy sink of the kidney. They suggest that the oxidation of glutamine supplies energy for tubular transport and basal demands such as synthesis of hormones and maintenance of structure, whereas the oxidation of lactate supplies energy mainly for transport activities. The oxidative metabolism of the kidneys differs from that of other organs in at least two respects. First, the kidneys extract much less oxygen from each 100 ml of arterial blood than other organs do: on average, 1.5 ml in comparison with 4-15 ml (1). Second, the extraction of oxygen remains relatively constant at 1.5 ml/100 ml even though flow is reduced to as little as one-third of normal (2). The first difference does not mean that the energy cost of renal function is small. Blood flow and oxygen consumption are both large. The kidneys, which together constitute 0.5% of body weight, consume 5-8% of the oxygen consumed by the entire body at rest (1). Renal blood flow averages 20-25% of cardiac output at rest (1). The second difference derives from the fact that at normal perfusion pressures, the kidneys filter large volumes of plasma through their glomeruli and then face the energy-demanding task of actively reabsorbing the bulk of the components of the filtrate (3-9). In contrast, low perfusion pressure is commonly associated with low filtration rate and low rate of energy expenditure for reabsorption.Most renal physiologists believe that the major energy cost of renal function is related to the cost of reabsorbing sodium. It has been estimated that 20 to 30 sodium ions are reabsorbed for each molecule of oxygen consumed (3-9). Thus, in man, approximately 28,000 meq of sodium, contained in the 200 liters of plasma filtered each day, are reabsorbed at an energy cost equivalent to the consumption of 1200 mmol of oxygen (1). Energy must also be expended in biosynthesis of hormones and in maintenance of cellular structure.The experiments described in this paper were designed to measure the utilization of glutamine and lactate as fuels of do...

Localization of members of MCT monocarboxylate transporter family Slc16 in the kidney and regulation during metabolic acidosis

“…Conversely, lactate can serve as a substrate for further oxidation and thus, energy production in cells that are not in an anaerobic state. Lactate utilization supports renal transport activity and appears to be stimulated during alkalosis and reduced during acidosis (3). Depending on the energy and oxidative capacity of a cell, lactate can either be extruded from the cytosol or, inversely, taken up by the cell.…”

Isolation of tumor-secreted products from human carcinoma cells maintained in a defined protein-free medium.

“…It is used as a major energy source by both kidney and intestinal tissues in vivo (24)(25)(26). The latter observation is relevant to the observed survival capacity of established colon carcinoma lines in our glutamine-supplemented medium.…”