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Abnormal erythrocyte pyrimidine nucleotides in uremic subjects
Nephron
|January 1, 1985
Summary
Uremic red blood cells (RBCs) show increased purine nucleotides and abnormal pyrimidine nucleotides, specifically cytidine diphosphate-choline (CDP-C) and cytidine diphosphate-ethanolamine (CDP-E). This finding may indicate a shared mechanism contributing to hemolysis in chronic kidney disease.
Area of Science:
- Biochemistry
- Hematology
- Nephrology
Background:
- Uremia significantly elevates erythrocyte (RBC) purine nucleotides, linked to phosphate retention.
- Pyrimidine nucleotides are typically absent in healthy RBCs.
- Abnormal RBC pyrimidine nucleotides have been observed in hemolytic anemias and lead poisoning.
Purpose of the Study:
- To investigate the presence and identity of pyrimidine nucleotides in uremic RBCs.
- To explore the potential link between these nucleotide abnormalities and RBC membrane dysfunction in uremia.
Main Methods:
- High-performance liquid chromatography (HPLC) of hemolysates from uremic adults.
- UV spectroscopy and 31P nuclear magnetic resonance (NMR) for nucleotide identification.
Main Results:
- Uremic RBC hemolysates showed a 50% increase in purine nucleotides.
- Abnormal pyrimidine nucleotides, identified as cytidine diphosphate-choline (CDP-C) and cytidine diphosphate-ethanolamine (CDP-E), were detected at ~10% of purine nucleotide concentrations.
- These findings were independent of dialysis status, medications, or RBC pyrimidine 5'-nucleotidase activity.
Conclusions:
- CDP-C and CDP-E are the predominant abnormal pyrimidine nucleotides in uremic RBCs.
- While potentially an epiphenomenon of phosphate retention, the accumulation of these nucleotides suggests a common pathway contributing to accelerated hemolysis in chronic renal insufficiency.