Antiproteinuric therapy reduces prothrombotic state in certain patients
MedWire News: Antiproteinuric therapy reverses the prothrombotic state in patients with overt proteinuria and stable renal function, study findings indicate.
The association between the extent of proteinuria and changes in plasma levels of various coagulation proteins has been considered "textbook knowledge", but solid evidence is lacking, say Bakhtawar Mahmoodi (University Medical Center Groningen, The Netherlands) and colleagues.
Furthermore, it is unknown whether these coagulation disturbances resolve with antiproteinuric therapy, they add.
Mahmoodi and team therefore assessed the impact of renin-angiotensin system-inhibiting antiproteinuric therapy on levels of pro- and anticoagulant proteins and thrombin generation, in 32 patients with overt proteinuria (median 3.7 g/day).
The patients were enrolled in a crossover trial in which they were treated for 6-week periods with placebo, losartan, and losartan plus the diuretic hydrochlorothiazide, in combination with either a high- or low- sodium diet, in a random order.
The researchers report, in the Journal of Thrombosis and Haemostasis, that the mean proteinuria level, adjusted for gender, age, creatinine clearance, and haematocrit, fell significantly from 2.7 g per day during the placebo period, to 0.8 g per day during maximum treatment (losartan plus hydrochlorothiazide).
There was a corresponding reduction in levels of the procoagulant proteins fibrinogen and factor V, which fell from 4.0 g/l and 135% to 3.6 g/l and 120%, respectively.
Mean levels of the anticoagulant proteins C and free protein S also fell significantly with maximum antiproteinuric therapy, but total protein S, factor VIII, Von Willebrand factor, and antithrombin levels were unchanged.
In addition, the team found that mean prothrombin fragment 1+2 levels and activated protein C resistance were significantly lower during maximum treatment compared with the placebo period.
However, for thrombin generation, only peak thrombin in the presence of thrombomodulin was significantly lower during maximum treatment compared with the placebo period. Adjusted mean levels of other calibrated automated thrombogram parameters (lag time, time to peak, and velocity index) were similar during both periods.
The researchers also noted that patients were significantly more prothrombotic - as judged by higher levels of fibrinogen, factor V, factor VIII, and Von Willebrand factor - than 32 age- and gender-matched healthy controls.
"One can argue that the observed amelioration in the coagulation disturbance may be a direct effect of renin-angiotensin system inhibition by losartan instead of proteinuria reduction, or by the altered volume status. However, based on the literature, and our creatinine clearance and haematocrit adjusted results, it is likely that the observed amelioration in coagulation disturbances is due to the proteinuria reduction [itself]," Mahmoodi and co-authors conclude.
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By Laura Dean