الفهرس | Only 14 pages are availabe for public view |
Abstract Diabetic nephropathy is a clinical syndrome in people with diabetes, characterized by albuminuria (>300 mg/d or 200 μg/min) on at least two occasions separated by 3-6 months. Diabetic nephropathy is usually accompanied by hypertension, progressive rise in albuminuria to reach frank proteinuria, and decline in renal function (Chiarelli et al., 2009). Diabetic nephropathy affects about 15 to 25% of type 1 diabetic patients and 30 to 40% of patients with type 2 diabetes ( Nelson et al., 2008). Three major pathologic changes occur in the glomeruli of persons with diabetic nephropathy. First, mesangial expansion is directly induced by hyperglycemia, perhaps via increased matrix production or glycosylation of matrix proteins. Second, thickening of the glomerular basement membrane (GBM) occurs. Third, glomerular sclerosis is caused by intraglomerular hypertension (induced by dilatation of the afferent renal artery or from ischemic injury induced by hyaline narrowing of the vessels supplying the glomeruli). These different histologic patterns appear to have similar prognostic significance (Mauer and Fioretto, 2007). The angiopoietins have been recognised mostly for their involvement in endothelial activation, angiogenisis and inflammation the major processes which lie at the core of atherogenisis, and so the angiopoietins/Tie2 system has been identified as a potential new player in pathogenesis of CKD associated atherosclerosis (Fiedler and Augustin, 2006). Summary and Conclusion 124 Upregulation of renal Ang-2 levels and decreased Ang-1/Ang-2 ratio accompanied by glomerular monocytes/macrophage infiltration were observed in mouse type 1 and type diabetic nephropathy models (Ichinose et al., 2005). The aim of the current study is to evaluate the level of plasma angiopoietin-1 in the patients with diabetic nephropathy. And to study the relation between serum angiopoietin-1 and the severity of renal dysfunction in the patients with diabetic nephropathy. The current study was conducted on 45 diabetic patients and 15 control subjects selected from the internal medicine department and outpatient clinic of endocrinology of Ain Shams University. These patients were divided into three groups as regards to the level of albumminuria and the fourth group was the control group as followed: Group 1(microalbuminuria group) It includes 15 patients with diabetic microalbuminuria, Group 2 (macroalbuminuria group) It includes 15 patients with diabetic macroalbuminuria, Group 3 (normoalbuminuria group) It includes 15 patients with diabetic normoalbuminuria and Group 4 (control group) It includes 15 healthy control subjects. All subjects were subjected tho thefollowing: 1- full medical history taking includind age, sex, diabetes type, medication intake, presence of any diabetic complications or other diseases that can cause renal injery. 2- throughout clinical examination. 3-Laboratory investigations: complete urine analysis, albumin\creatinine ratio, serum creatinine, eGFR and serum angiopoietin-1. 4- ultrasound examination of abdomen and pelvis Summary and Conclusion 125 to assess kidney shape and size and any abnormalities consistent with kidney disease and to exclude obstructive uropathy. The results were statistically analysed and we observed the following: There was no significant difference between the four groups as regardind sex(P = 0.568), age (P = 0.170), body weight (P = 0.331) or diabetes type (P = 0.659). Regardindg serum creatinine: Compared to control group, it was significantly higher in macroalbuminuria group (1.14 ± 0.22 vs 0.89 ± 0.1) mg/dl respectively. Also, it was significantly higher in macroalbuminuria compared to microalbuminuria (1.14 ± 0.22 vs 0.97 ± 0.13) mg/dl respectively and normoalbuminuria groups (1.14 ± 0.22 vs 0.89 ± 0.09) mg/dl respectively. Regarding eGFR: Compared to control group, it was significantly lower in macroalbuminuria group (76.16 ± 11.44 vs 98.81 ± 14.09) ml/min/1.73mm2 respectively. Also it was significantly lower in macroalbuminuria compared to microalbuminuria (76.16 ± 11.44 vs 89.58 ± 14.6) ml/min/1.73mm2 respectively and normoalbuminuria groups (76.16 ± 11.44 vs 96.28 ± 11.63) ml/min/1.73mm2 respectively. Regarding albumin\creatinine ratio: In comparison to control group, it was significantly higher in macroalbuminuria group (1409.7 ± 907.0 vs 14.1 ± 6.7) μg/mg respectively. It was significantly higher in macroalbuminuria group compared to the normoalbuminuria group (1409.7 ± 907.0 vs 11.1 ± 8.0) μg/mg respectively and microalbuminuria group (1409.7 ± 907.0 vs 153.2 ± 75.6) μg/mg respectively. Summary and Conclusion 126 Regarding serum angiopoietin-1: Compared to control group, it was significantly higher in normoalbuminuria group (1176.3 ± 747.8 vs 3155.0 ± 2446.3) pg/ml respectively and significantly lower in macroalbuminuria group (3078.3 ± 551.4 vs 3155.0 ± 2446.3) pg/ml respectively. It was significantly higher in normoalbuminuria group compared to microalbuminuria group (1176.3 ± 747.8 vs 4776.5 ± 1349.8) pg/ml respectively and macroalbuminuria group (1176.3 ± 747.8 vs 3078.3 ± 551.4) pg/ml respectively. Also, it was significantly higher in microalbuminuria compared to macroalbuminuria group (4776.5 ± 1349.8 vs 3078.3 ± 551.4) pg/ml respectively. There was significant inverse correlation between serum angiopoietin-1 and both serum creatinine (r = -0.341) and urine albumin creatinine ratio (r = -0.497) , while there was significant direct correlation between serum angiopoien-1 and eGFR (r = 0.330). There was no significant correlation between Angiopoietin-1 and age, sex or body weight (p > 0.05). Summary and Conclusion 127 Conclusion Decrease of serum Angiopoitin-1 level in patients with diabetic nephropathy may play a big role in pathogenisis of the disease especially because serum angiopoietin-1 is decreasing more with the progression of the proteinuria. Hence this conclusion may implement angiopoietin-1 in experimental treatment studies to prevent or improve diabetic nephropathy or to study the cause effect relationship of serum angiopoietin-1 and diabetic nephropathy to use angiopoietin-1 as a diagnostic tool for diabetic nephropathy disease. |