The role of Ectonucleotidases Pathway (CD39/CD73) in Childhood Renal Failure

Background and Aim: Chronic renal failure (CRF) is defined as an irreversible reduction in glomerular filtration rate (GFR). In children, CRF may be the result of congenital, acquired, inherited or metabolic renal disease. In addition to progressive injury with ongoing structural/ metabolic genetic diseases, renal injury may progress despite removal of the original insult. The clinical presentation of CRF is quite varied and dependent on the underlying renal disease. Hypoxia is considered as the master factor in the pathogenesis of renal failure. In the last few years, studies have demonstrated the protective anti-inflammatory role of CD39/CD73 molecules pathway during hypoxia. CD39 and CD73 molecules have been described on circulating T lymphocytes, endothelial cells and minimally, expressed on granulocytes. CD39, (ectonucleotidase triphosphate diphosphohydrolase 1, ENTPD1) is responsible for the conversion of proinflammatory ATP to ADP and AMP whereas CD73 (ecto-5'-nucleotidase) converts AMP into adenosine. Adenosine plays a central role in tissue protection via anti-inflammatory and immune modulatory effect. We aimed to assess the role of CD39/CD73 axis in immuno-inflammatory pathogenesis of renal failure. Also, we aimed to define the expression pattern of both phenotypes on circulating T lymphocytes. Patients and method: This cross sectional study was conducted at Al Zahraa University Hospital from December 2011 to May 2012. An informed consent was obtained from parents of all children. The study included twenty children with chronic renal failure, (on regular hemodialysis) and twenty apparently healthy children as control group. The routine laboratory investigations were performed for patients (blood urea, serum createnin,serum alkaline phosphatase and complete blood count). Using flowcytometry, the patients and control groups were investigated for the frequency of CD39 and CD73 T lymphocytes. In addition, C-reactive protein (CRP) was performed for patients as inflammatory marker. Results: We found that both CD39% and CD73% of patient group were significantly lower than those of control Group. In patient group, we observed that both CD39% and CD73% were negatively correlated to blood urea.Also,CD73% was negatively correlated to serum createnine. In addition, patient group showed negative correlation between CRP as an inflammatory marker and the percentage of both CD39/CD73.Furthermore, there was negative correlation between CD73% and serum alkaline phosphates. Conclusion: The significant decline in both CD39 and CD73 molecules on patients T lymphocytes confirmed the relation between down modulation of ectonucleotidases and deregulation of renal immunological/inflammatory cascade. Also, the negative correlation between both molecules and blood urea proved that CD39/CD73 deficiency can impact renal function. Moreover, the negative relation between CRP and the mean percentages of both phenotypes revealed the protective anti- inflammatory role of the pathway. (Nahla M Abd-Elaziz and Ateyat A Ateya. (The role of Ectonucleotidases Pathway (CD39/CD73) in Childhood Renal Failure. ) Life Sci J 2012;9(4):2135-2140) (ISSN: 1097-8135). http://www.lifesciencesite. com. 318