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

Abstract

Net renal transport (T_α-kg) and renal utilization (Q_α-kg) of infused α-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 α-KG dissimilation. T_α-kg sums brisk reabsorptive (–T_α-kg) and sluggish secretory (+T_α-kg) phenomena, localized to the proximal tubule. –T_α-kg is markedly decreased or reversed to +T_α-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_α-kg can occur independently of changes in Q_α-kg, indicating that metabolism and transtubular transport of α-KG may be separate: T_α-kg changes spontaneously while Q_α-kg remains relatively stable; probenecid reduces Q_α-kg while not affecting T_α-kg; alkalosis causes parallel decreases in both T_α-kg and Q_α-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 α-KG for transtubular transport, and independently, with α-KG for renal utilization.