Abstract
The proximal tubular uptake and utilization of aketoglutarate (αKG) has been linked to corticalblood flow, H+ secretion and anaerobic CO2 production. Oxidation of aKG at the substrate level is the first step in energy-dependent gluconeogenesis by renal cortex. Thus, renal αKG dissimilation and renal glucose production (RGP), might reflect locus and extent of altered cell function in the kidney. To explore this, Na αKG was infused, with parental consent, in 10 children with renal disease (9 acute glomerulonephritis [AGN], I nephrotic) and 12 controls under standard loading, inulin and PAH clearance conditions. Renal extractions of PAH (EPAH) and αKG as well as RGP were determined from frequent concurrent samples of renal vein and aortic blood in 3 patients with AGN, the nephrotic, and 6 controls, with ‘normal’ kidneys but congenital heart defects. The studies were repeated in the 3 AGN patients during healing. Renal uptake and utilization of αKG and RGP were calculated for body size and estimated kidney weight. In vitro RGP by human kidney slices obtained at operation from 2 intact and 2 diseased kidneys also was assayed for comparison.
In AGN, significantly reduced renal uptake and utilization of the αKG load with persistently high H+ excretion and decreased reabsorption of Na accompanied the low CIN, EPAH and CPAH (CPAH/EPAH). All patterns approximated controls with healing. RGP usually was impaired, especially in the nephrotic child. RGP with αKG in vivo was similar to in vitro values for ‘normal’ human kidney slices with glycerol, fructose, pyruvate, αKG, succinate or malate as substrates. These results imply increased ‘non-cortical’ renal blood flow and impaired proximal tubule metabolism referrable to αKG in the kidney diseases studied. (APS)
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Metcoff, J., Ort, M., Scharer, K. et al. 46 Renal Metabolism with Renal Disease in Man. Pediatr Res 1, 212 (1967). https://doi.org/10.1203/00006450-196705000-00053
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DOI: https://doi.org/10.1203/00006450-196705000-00053