الفهرس 
DIABETIC KIDNEY DISEASEOnly 14 pages are availabe for public view
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Abstract
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of different organs. Type 2 diabetes mellitus is the most prevalent form of diabetes and accounts for 90% of cases globally.
Diabetic kidney disease is a common complication of diabetes mellitus and a significant cause of chronic kidney disease and end-stage renal failure globally. In clinical practice, estimated glomerular filtration rate (eGFR) and albuminuria are used to assess renal function.
Tumor necrosis factor-α (TNF-α) is a functional 26-kDa homotrimer type II transmembrane protein. It is a central proinflammatory cytokine that is generated in a wide variety of cells, including hematopoietic cells (monocytes, macrophages, and T cells), fat and endothelial cells. The effects of TNF-α are mediated by two cell-surface receptors, tumor necrosis factor receptor1(TNFR1) and tumor necrosis factor receptor 2 (TNFR2). TNFR1 is present in normal glomeruli and is found to be upregulated on infiltrating leukocytes in response to renal injury.
The aim of our present study was to determine serum concentration of soluble TNF receptor-1 (sTNFR1) in patients with type 2 DM and correlating it with various clinical and laboratory variables laying stress on kidney functions. We also tried to find if it can be used as an early predictor of renal dysfunction. This work was conducted on 90 type 2 diabetic patients; 45 patients with eGFR <60 ml/min/1.73m2 and 45 patients with eGFR ≥ 60 ml/min/1.73m2.
Type 2 diabetes mellitus was diagnosed based on the American Diabetes Association criteria. All studied patients were subjected to detailed history taking with special focus on renal complications and a thorough physical examination. Serum sTNFR1, lipid profile, urea, creatinine, HbA1c, FBS and ACR were estimated. Also, BMI and eGFR were calculated for all patients included.
In our study, serum sTNFR1 showed a highly significant increase in type 2 diabetic patients with eGFR <60 ml/min/1.73m2 compared to the patients with eGFR ≥ 60 ml/min/1.73m2.
On comparing type 2 diabetic patients with eGFR <60 ml/min/1.73m2 to the patients with eGFR ≥ 60 ml/min/1.73m2 regarding the clinical and laboratory parameters, we found a significant higher results in age, BMI and ACR in the former group.
A correlation study was performed between serum levels of sTNFR1 and other studied clinical and laboratory parameters. This study detected a significant positive correlation between sTNFR1 and TC, TG, LDL, ACR and BMI while there was a significant negative correlation between sTNFR1 and both HDL and eGFR in type 2 diabetic patients with eGFR <60 ml/min/1.73m2.
Moreover, binary logistic regression analysis revealed that only sTNFR1 is a significant predictor of eGFR< 60 ml/min/1.73m2. Also, by using multivariate multiple regression analysis of factors affecting eGFR among patients with eGFR<60 ml/min/1.73m2, it showed that only sTNFR1 has a significant effect on eGFR.
Furthermore, receiver operator characteristics (ROC) curve was constructed and the best cutoff point of serum sTNFR1 as predictor of eGFR <60 ml/min/1.73m2 was found to be >500pg/ml where area under curve (AUC) = 0.938. At this cutoff sensitivity was 95.6% and specificity was 84.4%.
In conclusion, high serum sTNFR1 level is strongly associated with renal dysfunction in patients with type 2 diabetes mellitus. The assessment of its level could be beneficial in prediction and prevention of this pathological state and its unfavorable consequences which include end stage renal disease. Hence, this study introduces sTNFR1 as a plausible predictor of renal dysfunction in patients with type 2 diabetes mellitus.