대한신장학회

논문분류	춘계학술대회 초록집
제목	CIRCULATING MICRORNA 17 HOST GENE PROTEIN AND TUMOR NECROSIS-ALPHA IN PATIENTS WITH RENAL TRANSPLANTATION: RELATION TO ALLOGRAFT FUNCTION AND SURVIAL
저자	Hayam El Aggan* 1, Sabah Mahmoud2, Mohamed Saker1
출판정보	2016; 2016(1):
키워드	Chronic allograft dysfunction, MicroRNA 17 Host Gene Protein , Tumor necrosis factor-alpha
초록	Background: Chronic allograft dysfunction (CAD) remains the leading cause of late graft loss after kidney transplantation. MicroRNAs (miR) are small (19-25 nucleotides) noncoding RNAs that regulate gene expression of diverse biological processes. The polycistronic miR-17~92 cluster is comprised of six miRs and its primary transcript may also encode for a polypeptide of 70 amino acids designated as the miR-17 host gene (MIR17HG) protein. Tumor necrosis factor-alpha (TNF-alpha) is a homotrimer 34 kilodalton (kDa) type II transmembrane protein that is produced primarily by immune cells such as macrophages, dendritic cells, and T lymphocytes. It is a pleiotropic cytokine playing an essential role in the molecular basis of inflammatory and immunological reactions. So the aim of this work was to evaluate the plasma levels of MIR17HG protein,an index of miR-17~92 cluster activity, and the plasma level of TNF-alpha in patients with renal transplantation in relation to renal allograft function and survival. Methods: This study included 45 subjects; they were divided into three groups each 15, renal transplant patients with stable renal function (Group I), with CAD (Group II) and healthy subjects as controls (Group III). Quantitative determination of plasma levels of MIR17HG protein and TNF-α were performed using enzyme linked immunoassay (ELISA).Renal function tests; blood urea, serum creatinine and estimated glomerular filtration rate (eGFR) using Abbreviated Modification of Diet in Renal Disease (MDRD) equation. urinary albumin/urinary creatinine ratio and C-reactive protein (CRP) were done. Doppler ultrasonography was used to measure renal hemodynamics and resistive index (RI) was calculated. Renal biopsy was done in patients with CAD. Results: MIR17HG protein and TNF-alpha levels were significantly higher in renal transplant especially patients with CAD than the controls. By plotting receiver-operating characteristic (ROC) curve, the sensitivity and specificity of MIR17HG protein and TNF-alpha in discriminating renal transplant recipients with stable allograft function from those with CAD were 86.7% and 86.7% respectively at a cut-off level of 169.7 pg/ml for MIR17HG protein and were 73.3% and 86.7% respectively at a cut-off level of 200 pg/ml. for TNF-alpha, In patients with renal transplantation MIR17HG protein and TNF-alevel were positively correlated with each other and with serum creatinine, urinary albumin/creatinine ratio and CRP and was negatively correlated with e-GFR. The MIR17HG protein was positively correlated with the renal hemodynamic changes (RI). The degree of fibrosis in renal biopsy was positively correlated with MIR17HG protein and TNF-α levels (P<0.05). Conclusion: MIR17HG Protein and TNF-alpha plasma levels can be served as circulating biomarkers for early detection of renal allograft dysfunction and also for follow up of patients with renal transplantation. They also can act as a pro-fibrotic factor and denoting ongoing inflammation in the pathogenesis of CAD.
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