Our previous study showed that active oxygen radicals generated from a Fenton system and a xanthine plus xanthine oxidase system caused serious loss of in vivo bioactivity of recombinant human erythropoietin (EPO), a highly glycosylated protein. In the present study, we characterized the oxidative modifications to the protein and carbohydrate moiety of EPO, which lead to a reduction of its bioactivity. In vitro bioactivity was reduced when EPO was treated with oxygen radicals generated from a Fenton system in the presence of 0.016 mM H2O2, and the reduction was directly proportional to the loss of in vivo bioactivity. SDS-PAGE analysis showed that dimer formation and degradation was observed under more severe conditions (Fenton reaction with 0.16 mM H2O2). The tryptophan destruction was detected at 0.016 mM H2O2 and well correlated with the loss of in vitro bioactivity, whereas loss of other amino acids were occurred under more severe conditions. Treatment with the Fenton system did not result in any specific damage on the carbohydrate moiety of EPO, except a reduction of sialic acid content under severe condition. These results suggest that active oxygen radicals mainly react with the protein moiety rather than the carbohydrate moiety of EPO. Destruction of tryptophan residues is the most sensitive marker of oxidative damage to EPO, suggesting the importance of tryptophan in the active EPO structure. Deglycosylation of EPO caused an increased of susceptibility to oxygen radicals compared to intact EPO. The role of oligosaccharides in EPO may be to protect the protein structure from active oxygen radicals.
Proteinuria which is a marker of renal insufficiency is common among adult SCA patients, and routine screening for proteinuria may help detect those at increased risk of renal disease. CKD prevalence is high among SCA patients with significant proteinuria.
Despite positive economic forecasts, stable democracies, and reduced regional conflicts since the turn of the century, Africa continues to be afflicted by poverty, poor infrastructure, and a massive burden of communicable diseases such as HIV, malaria, tuberculosis, and diarrheal illnesses. With the rising prevalence of chronic kidney disease and kidney failure worldwide, these factors continue to hinder the ability to provide kidney care for millions of people on the continent. The International Society of Nephrology Global Kidney Health Atlas project was established to assess the global burden of kidney disease and measure global capacity for kidney replacement therapy (dialysis and kidney transplantation). The aim of this second iteration of the International Society of Nephrology Global Kidney Health Atlas was to evaluate the availability, accessibility, affordability, and quality of kidney care worldwide. We identified several gaps
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