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.