Potential role of thrombin-activatable fibrinolysis inhibitor [TAFI] in diabetic nephropathy and its relation to degree of albuminuria and to dialysis modality

ABSTRACT

Diabetic nephropathy has become the most prevalent cause of end-stage renal disease [ESRD] in many countries, and about one third of patients with diabetic nephropathy progress to end stage renal disease. Patients with end-stage renal disease dialyzed due to diabetic nephropathy are at higher risk of death due to cardiovascular complications than dialyzed non-diabetic patients. Hypofibrinolysis is a common finding in patients with diabetes mellitus and a risk factor for diabetic nephropathy and may play a role in the vascular complications in dialyzed diabetic patients. A new potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor [TAFI], has been isolated from human plasma. However, the relation between plasma TAFI level and diabetic nephropathy has not been well appraised. In the present study, we investigated the plasma levels of TAFI in 50 type 2 diabetic patients 10 with normoalbuminuria, 10 with microalbuminuria, 10 with macroalbuminuria, 10 with ESRD on haemodialysis, and 10 with ESRD on peritoneal dialysis. Also, we assessed albumin/creatinine ratio in albumiuric patients, blood urea, serum creatinine, serum lipids, and ECG. The plasma level of TAFI in diabetic patients with macroalbuminuria was significantly higher than the level in diabetic patients with microalbuminuria [P < 0.00l], and higher in micro-albuminuric patients than in normolbuminuric patients[P < 0.00l]. Plasma TAFI level was correlated to albumin/craetinine ratio[P < 0.00l], blood urea[P < 0.00l] and serum creatinine[P < 0.00l] in patients with micro-albuminuria [non dialyzed patients]. Moreover, it was significantly higher in patients with diabetic nephropathy and on peritoneal dialysis than those on haemodialysis [P < 0.01] and it was correlated positively with triglycerides [P < 0.05] and negatively with HDL-c[P < 0.05]. These data suggest that TFAI level was increased by the progression of diabetic nephropathy as it was significantly higher in. patients reaching ESRD [haemodialysis and peritoneal dialysis groups]than in those still in the stages of micro and rnacro-albuminuria and higher in macroalbuminuric patients than in microalbuminuric patients. Also TAFI level was significantly positive correlated with tile indicators of decline in renal function [blood urea, serum creatinine, urinary albumin and urinary albumin/creatinine ratio]. So we can concluded that increased plasma level of TAFI may contribute to the pathogenesis and progression of diabetic nephropathy and may have role in tile cardiovascular complications of dialyzed diabetic patients, especially those under peritoneal dialysis