Effect of obstruction of renal metabolism. Renal tissue metabolite concentration after alpha-ketoglutarate infusion.

beta-Hydroxybutyrate and/or alpha-ketoglutarate were infused into awake, resing dogs after varying periods of unilateral ureteral obstruction. The animals were then anesthetized, and the kidneys rapidly excised and frozen in liquid nitrogen. While maintained at temperatures below -60 C, the frozen kidneys were separated into cortical and medullary fractions. The concentrations of alpha-ketoglutarate, glutamate, lactate, pyruvate, citrate, and malate were determined in both cortical and medullary renal tissue. The induction of reversible renal damage by 2 weeks of obstruction was associated with decreased ability to accumulate alpha-ketoglutarate after alpha-ketoglutarate and/or beta-hydroxybutyrate infusion. The induction of irreversible renal damage by 6 weeks of obstruction was associated with the inability to produce or accumulate (i) alpha-ketoglutarate, (ii) lactate, (iii) citrate, or (iv) malate after infusion of alpha-ketoglutarate and/or beta-hydroxybutyrate. The metabolic changes induced by unilateral ureteral obstruction indicatr that aerobic metabolism is inhibited with the virtual elimination of many aerobic reacions in the irreversibly damaged kidney. The reversibly damaged kidney is capable carrying on certain aerobic reactions but usually at a diminished rate. Differences in the extent and character of the metabolic changes induced by ureteral obstruction may make it possible to predict the degree of renal damage and, therefore, recoverability.