Study of plasma level of thrombin-activatable fibrinolysis inhibitor TAFI) in diabetic nephopathy with and without dialysis

Faculty Medicine Year: 2005
Type of Publication: Theses Pages: 144
Authors:
BibID 3209127
Keywords : Internal Medicine    
Abstract:
SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum lipids (total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol) were measured and ECG was performed.Diabetics with diabetic nephropathy had significant higher plasma TFAI level than those without nephropathy. Also, increase in TAFI level was found with progression in diabetic nephropathy; was significantly higher in patients reaching the end stages renal failure (hemodialysis and peritoneal dialysis groups) than in those still in the stages of micro- and macro- albuminuria, and higher in macroalbuminuric patients than in microalbuminuric patients.TAFI level was positively correlated with the indicators of decline in renal function and progression of diabetic nephropathy such as urinary albumin, albumin/creatinine ration, blood urea and serum creatinine. TAFI was strongly correlated with albumin/creatinine ratio much more than with urinary albumin suggesting that albumin/creatinine ratio may be a more precise measure for detection of albuminuria and decline in renal function in diabetic patients than urinary albumin.TAFI level was found to be significantly higher in dialyzed patients with diabetic nephropathy than in those still not starting dialysis and correlated positively with duration of dialysis and markers of dialysis inadequacy (raised urea and creatinine). Moreover, it was significantly higher with peritoneal dialysis than with hemodialysis in patients with diabetic nephropathy and on regular dialysis therapy.Level of TAFI was correlated positively with triglycerides and negatively with HDL-cholesterol in a significant manner in all patients with diabetic nephropathy but not in control subjectsFrom this study, it could be concluded that:1- Patients with diabetic nephropathy have elevated circulating TAFI concentration which is more obvious with the progression of the nephropathy and it is correlated with markers of decline in renal function; a finding that suggests the contribution of TAFI in the pathogenesis and progression of diabetic nephropathy through inhibition of fibrinolysis and subsequent enhancement of fibrin deposition in the renal glomeruli.2- Diabetics with diabetic nephropathy on peritoneal dialysis have a higher concentration of TFAI more than those who shifted to hemodialysis program. This may contribute to the higher cardiovascular mortality in this population.3- It is better to screen for microalbuminuria and to assess kidney function in patients with diabetes mellitus by using albumin/creatinine ratio than by urinary albumin excretion.At the end, after finishing this work, it could be recommended to do further studies considering the following:• Longitudinal study of TAFI in the same patients progressing in different stages of diabetic nephropathy• Whether TFAI inhibitors like Potato Tuber-derived Carboxypeptidase Inhibitor (PTCI) could regress the devolvement of renal failure in patients in early stages of diabetic nephropathy or not. Also, effects of PTCI on regression or prevention of atherosclerotic cardiac diseases in patients with diabetic nephropathy especially in those on peritoneal dialysis should be studied.SUMMARY, CONCLUSIONS AND RECOMMENDATIONSThe present study has been conducted with two objectives in mind; first is to detect if there is a role for Thrombin-Activatable Fibrinolysis Inhibitor, TAFI (a new potent inhibitor of fibrinolysis) in the pathogenesis and progression of diabetic nephropathy and to clarify some of factors that might be responsible-among others- for the vulnerability of patients with diabetic nephropathy to the high morbidity and mortality that has been reported in these patients. Second is to find whether TAFI level in patients dialyzed due to diabetic nephropathy is affected or not by the modality of dialysis and thereby influences cardiovascular morbidity among these patients.Forty type 2 diabetic patients in different stages of diabetic nephropathy were studied. They comprised four groups according to stage of diabetic nephropathy and according to modality of dialysis in those reaching ESRD; 10 type 2 diabetics in microalbuminuric stage, 10 type 2 diabetics in macroalbuminuric stage, 10 type 2 diabetic in end stage renal disease on regular hemodialysis, and 10 type 2 diabetic in end stage renal disease on regular peritoneal dialysis. In addition, 10 type 2 non-renal normotensive diabetic cases served as controls.All groups were matched in age and sex and all had liver enzymes, uric acid and serum electrolytes within the normal range.Plasma TAFI levels, using ELISA technique, were measured in a fasting venous blood samples. The following parameters of renal function were assessed; urinary albumin and albumin/creatinine ratio in albumiuric groups, blood urea, and serum creatinine. In addition, serum 
   
     
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  • Mohammed Hussien Elsaid Hussien, "Study of plasma level of thrombin-activatable fibrinolysis inhibitor TAFI) in diabetic nephopathy with and without dialysis", 2005 More

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