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Abstract Summary Diabetic Nephropathy (DN) remains the leading cause of end stage renal disease (ESRD) in the Western world, responsible for nearly half of all new ESRD cases in the USA, in type 2 diabetic patients, the incidence of microalbuminuria was 2.0% per year and the prevalence 10 years after diagnosis 25% in the (UKPDS) study, the prevalence of proteinuria is highly variable, ranging from 5 to 20%. Once persistent microalbuminuria is confirmed, 20 to 50% of type 2 diabetic patients will progress to DN. Macroalbuminuria will eventually lead to an end-stage renal insufficiency within 10 to 20 years. Microalbuminuria is currently the only diagnostic tool available for early diagnosis of diabetic nephropathy. The test is based on immunological detection of small quantities of albumin in the urinary samples of diabetes patients. Although the measurement of Urinary albumin excretion (UAE) is the cornerstone for the diagnosis of diabetic nephropathy, there are some patients with either type 1 or type 2 diabetes, who have decreased glomerular filtration rate (GFR) in the presence of normal UAE. There are several limitations of the use of microalbuminuria as an index of renal function. It is therefore desirable to identify additional protein markers that would augment prediction of diabetic nephropathy. Identifying modifiable factors that cause increase in UAE is important since intervention directed to these factors might be expected to result in better renal and cardiovascular prognosis. 188 Summary Vasopressin has been hypothesized as one of these modifiable factors, Vasopressin is known as antidiuretic hormone, despite its importance for normal water regulation in the body. Vasopressin also has been reported to exert deleterious effects on the kidney. Vasopressin is elevated in DM and in some forms of hypertension. Due to the fact that direct measurement of vasopressin in humans is problematic, recently, an assay has been developed to measure copeptin, the C-terminal portion of the precursor of AVP (arginine vasopressin), Copeptin is secreted with vasopressin, and hence it can be used as a surrogate marker of the AVP system. In 2010, Meijer et al report a positive cross-sectional association between plasma copeptin and microalbuminuria within the population sample of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study, which includes adults both with and without kidney dysfunction (Massimo Cirillo.; 2010). The association of plasma copeptin with high urinary albumin excretion was not explained by high glomerular filtration rate (GFR), because individuals with high plasma copeptin actually had higher serum creatinine and lower estimated GFR in comparison with individuals with low plasma copeptin, they conclude that, in addition to its well-known antidiuretic effect, vasopressin might also exert per se an intrarenal pro-albuminuric effect We aimed to identify the possible relations of serum copetin level (a surrogate marker of vasopressin) with different stages of diabetic nephropathy according to UAE for further estimation of the role of serum copeptin level as a diagnostic novel biomarkers for early detection of protienuria in diabetic patients. 189 Summary Also, we aimed to investigate the possible relation between Serum Copeptin level and different stages of CKD in DN regarding decline in renal functions and estimated glomerular filtration rate that develop in diabetic patients. In our study, patients were recruited from referrals to the Internal Medicine outpatient clinic and nephrology outpatient clinic, Beni-Suef University Hospital. A population of 96 persons were included in this study, the study was divided into 5 groups; group (1) is the control group comprising 19 healthy subjects and group (2-5) comprising 80 diabetic patients (Type II) with different stages of albuminuria and CKD. All subjects have full battery of history, clinical examination, laboratory investigations, fundus examination, pelvi-abdominal ultrasound and estimation of serum copeptin level. Statistical analysis of demographic and clinical variables was performed among these groups. It was shown that serum copeptin level was significantly higher in diabetic patients than in controls and it correlates with the level of control of hyperglycemia as measured by level of HBA1C.this finding has not been discussed before in the literature. We found that serum copeptin level can predict the presence of microalbuminuria in type II diabetics; it can be used as a novel marker for early diagnosis of albuminuria in diabetic nephropathy. 190 Summary Serum copeptin level significantly correlates with the progression of albuminuria in DN from normo to microalbuminuria, in patients with diabetic nephropathy with normal kidney functions and this finding also has not been discussed before. We found that serum copeptin level in controls (group 1) correlated with its level in diabetic patients with normoalbuminuria and normal kidney functions (group 2), and correlated with its level in diabetic patients with microalbuminuria and normal kidney functions (group 3). Also, we found that serum copeptin level in diabetic patients with normoalbuminuria and normal kidney functions (group 2) correlated with its level in diabetic patients with microalbuminuria and normal kidney functions (group 3). So, serum copeptin level in diabetic patients group (3) correlated with its level in both groups (1 and 2). These types of comparisons with these findings in humans with diabetic nephropathy had not been discussed before in the literature. We found that diabetic patients with normoalbuminuria with or without decline in eGFR (Groups 2, 5) had a higher level of serum copeptin compared to controls (group 1) with highly statistically significant difference in between. Also we found that diabetic patients with microalbuminuria with or without decline in eGFR (Groups 3, 4) had the highest level of serum copeptin compared to both controls (group 1) and diabetic patients with normoalbuminuria with or without decline in eGFR (Groups 2, 5). This means that serum copeptin level correlates with the progression of albuminuria in different stages of diabetic nephropathy, 191 Summary even with or without the decline in eGFR. This finding was also novel and it was not discussed before in humans with diabetic nephropathy We correlated between serum copeptin levels versus different variables by using multivariate analysis among microalbuminuria group and we found that albuminuria, eGFR and HbA1c, respectively, were considered independent variables affecting serum copeptin level. Also in our results there was no statistically significant difference between males and females as regard serum copeptin level among all groups. We found that decrease in eGFR without albuminuria also correlates with serum copeptin level.this also has not been discussed before. We found that the presence of albuminuria together with decline in eGFR may add an influence to the level of copeptin in the serum of diabetic patients, as it was highest in this group of patients, in humans, in diabetics, to our knowledge these findings have not been discussed before. We found serum copeptin level in diabetic patients with microalbuminuria and overt renal impairment, (decline in eGFR, CKD stage 3, 4) (group 4) correlated with its level in groups (1, 2 and 3), while it didn’t show significant correlation with group (5). Also, we found that serum copeptin level in diabetic patients with normoalbuminuria and overt renal impairment (decline in eGFR, CKD stage 3, 4) (group 5) correlated with its level in groups (1, 2 and 3), while it didn’t show significant correlation with group (4).Also these findings were not discussed before in the literature. 192 Summary We also found that serum copeptin level correlated with the progression of the stages of chronic kidney disease in diabetics, these findings were discussed before in different studies, yet, all these studies were animal research work and not in humans. We correlated between serum copeptin level versus different variables by using multivariate analysis among groups with decline in eGFR (CKD stage 3, 4) with or without albuminuria, we found that albuminuria, eGFR and HBA1C, respectively, were considered independent variables affecting serum copeptin level. Hence, Serum copeptin level is considered better positive marker than negative with sensitivity 75% and specifity 40% and accuracy 52% in prediction of microalbuminuria in diabetics. Also, serum copeptin level is considered better positive marker than negative with sensitivity 76% and specifity 60% and accuracy 65 % in prediction of decline of eGFR in diabetics Finally, serum copeptin level is considered better positive than negative with sensitivity 83% and specificity 62% and accuracy 75% in prediction of global renal affection (both albuminuria and decline in eGFR) in diabetics. |