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Abstract SUMMARY iabetes mellitus is a metabolic disorder characterized by a state of chronic hyperglycemia resulting due to a disturbance in insulin secretion, action, or both, with a resultant long-term dysfunction of all organs, particularly the kidney. Diabetic nephropathy, or diabetic kidney disease, describes the chronic decline in kidney function occurring in diabetic patients. Management of patients with diabetic kidney disease poses a challenge to physicians. Diabetic kidney disease is an ongoing process that can progress despite adequate glycemic, blood pressure and proteinuria control. Therefore, the study of its pathogenic pathways is crucial to the development of new drugs that could slow its course. The progression of diabetic kidney disease is poorly predicted and assessed due to the scarcity of biomarkers in spite of the breakthrough in the management of diabetes mellitus. Urokinase-type plasminogen activator (uPA) is a serineprotease that converts inactive plasminogen to active plasmin. It also acts on urokinase-type plasminogen activator receptor (uPAR) expressed on the surface of different cells, including activated T-lymphocytes, monocytes, macrophages, megakaryocytes, keratinocytes, fibroblasts, endothelial cells, vascular smooth muscle cells and podocytes mediating various non-proteolytic processes. The soluble form of urokinase-type D Summary 92 plasminogen activator receptor (suPAR) is released from the cell membrane after the cleavage action of uPA on uPAR. Elevated serum suPAR levels were noticed in a wide range of diseases, including Diabetes Mellitus, focal segmental glomerulosclerosis, CKD, inflammatory disorders such as sepsis, cardiovascular diseases, cancers, autoimmune diseases, HIV infection and smoking. The aim of this study was to investigate the diagnostic value of suPAR in patients with diabetes mellitus, its role as an indicator of diabetic kidney disease, its correlation with biological parameters of kidney function and its capacity as a biomarker for renal impairment severity. This was a comparative cross-sectional study that was conducted at Diabetes Outpatient Clinic, Ain Shams University Hospitals on 180 diabetic patients with criteria of diabetic kidney disease according to American Diabetes Association (ADA) attending Ain Shams Diabetes Outpatient Clinic. They were divided into 70 diabetic patients with criteria of diabetic kidney disease, 70 diabetic patients without criteria of diabetic kidney disease and 40 healthy subjects. Study period was six months. Summary 93 The results of our present study can be summarized as follows: In the current study, the level of suPAR was significantly increased among the diabetic group than the control group. Our study showed that, the mean of age was 48.20 years in diabetic with DN group, 42.99 in Diabetic without DN and 41.50 in control group. Males were (80.0%) in diabetic with DN group and (71.4%) in diabetic without DN with no significant difference. In our study, there was no statistically significant difference between diabetic with DN, diabetic without DN and control groups regarding hypertension. Hypertension was present in 51.4% in diabetic with criteria kidney disease, 38.6% in diabetic without criteria kidney disease and 30.0% in control group. In this study, the level of suPAR was significantly higher among diabetic with DN group then diabetic without DN group than the control group (P=0.000). The present study revealed that eGFR was significantly lower among diabetic with DN group (40.59 ± 18.80) than diabetic without DN group (66.30 ± 25.57) and the control group (96.10 ± 22.41) (P=0.000). Summary 94 In this study, there were positive correlations between the level of suPAR and age , age of onset of DM , duration of DM , BMI , FBS , HBA1c, albumin/ creatinine ratio and serum creatinine. were There was negative correlation between suPAR and eGFR. While there were no statistically significant correlation berween suPAR and PPBS. Regarding the diagnostic accuracy of serum suPAR to differentiate between diabetic without DN group and diabetic with DN group, sensitivity was 65.71%, specificity was 90.0%, PPV was 86.8%, NPV was 72.4% and AUC was 0.860%. The cut off point to differentiate between patients with and without DN regarding suPAR level was 830 ng/l. |