Accelerated Purine Base Salvage — A Possible Cause of Elevated Nucleotide Pool in the Erythrocytes of Patients with Uraemia

Abstract

Erythrocytes from patients with uraemia invariably contain markedly increased ATP concentration¹. Other effects of uraemia on erythrocyte metabolism are: elevation of GTP, ITP and 2.3-DPG concentration^1–2, increased utilisation of glucose, higher lactate production or decreased Na/K dependent membrane ATP-ase activity^{3, 4}. There is no effect of haemodialysis on ATP in uraemic erythrocytes. Only renal transplantation or hypophosphatemic drug therapy causes reversal of this abnormality^{5, 6}. The haematological status of the uraemic patients is always very poor, which is a consequence both of slow regeneration of erythrocytes and the reduction of its half-life. Two possibilities are currently considered to explain the elevated ATP concentration. The first is the regulating effect of inorganic phosphate on nucleotide metabolism, which activates glycolysis and the pathways of purine synthesis and reutilisation and inhibits purine degradation^{4, 7–9}. The metabolic acidosis accompanying uraemia increases the influx of inorganic phosphate into the erythrocyte as well as is amplifying its effect¹⁰. The second reason could be the preponderance of younger red blood cells (RBC) in uraemic blood, which are known to contain higher concentrations of ATP^{11, 12}.