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

Abstract

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