Renal utilization and excretion of -ketoglutarate in dog: effect of alkalosis

¹ Department of Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York

Net renal transport (T_-kg) and renal utilization (Q_-kg) of infused -KG have been studied by renal clearance, stop-flow, and in vivo metabolic techniques in anesthetized (pentobarbital) dogs. The kidney is a major and specific site of -KG dissimilation. T_-kg sums brisk reabsorptive (–T_-kg) and sluggish secretory (+T_-kg) phenomena, localized to the proximal tubule. –T_-kg is markedly decreased or reversed to +T_-kg during either acute metabolic or respiratory alkalosis, indicating that extracellular fluid (ECF) pH and not intracellular fluid (ICF) pH is the common determinant. Changes in direction or magnitude of T_-kg can occur independently of changes in Q_-kg, indicating that metabolism and transtubular transport of -KG may be separate: T_-kg changes spontaneously while Q_-kg remains relatively stable; probenecid reduces Q_-kg while not affecting T_-kg; alkalosis causes parallel decreases in both T_-kg and Q_-kg, but of differing magnitudes in each. It is suggested that alkalosis alters extrarenal metabolism resulting in accumulation of substrate ions in blood which compete with -KG for transtubular transport, and independently, with -KG for renal utilization.