Abnormal erythrocyte pyrimidine nucleotides in uremic subjects

Uremia causes major increases in the erythrocyte (RBC) purine nucleotides, presumably secondary to phosphate retention, but no previous study has been made of the pyrimidine nucleotides, normally absent from RBC. This investigation was prompted by demonstration of the abnormal presence of RBC pyrimidine nucleotides, primarily cytidine triphosphate (CTP) plus cytidine diphosphate-choline (CDP-C) and cytidine diphosphate-ethanolamine (CDP-E), in two types of congenital hemolytic anemia as well as in lead poisoning. These observations suggested an analogy to the RBC membrane dysfunction of uremia. This is a report of the identification of CDP-C and CDP-E as the predominant abnormal pyrimidine nucleotides in the RBC hemolysates of uremic subjects. High performance liquid chromatography of hemolysates from uremic adults showed a 50% increase in purine nucleotides and the abnormal presence of pyrimidine nucleotides and diesters at approximately 10% of the concentration of the purine nucleotides. By means of UV spectra and ³¹P nuclear magnetic resonance, these were identified as CDP-C and CDP-E. The increased purine and abnormal pyrimidine nucleotides of uremic RBC were unrelated to the pre- or posthemodialysis state, allopurinol, levels of blood lead, copper and zinc, or RBC pyrimidine 5'-nucleotidase, the cytosolic enzyme that specifically dephosphorylates the pyrimidine nucleotides. Although the accumulation of CTP, CDP-C and CDP-E may be an epiphenomenon of phosphate retention, it also suggests a common pathway to the accelerated hemolysis of chronic renal insufficiency.