The impact of antiproteinuric therapy on the prothrombotic state in patients with overt proteinuria

Background: Overt proteinuria is a strong risk factor for thromboembolism, owing to changes in the levels of various coagulation proteins and urinary antithrombin loss. The described coagulation disturbances in these patients are based on outdated studies conducted primarily in the 1970s and 1980s. Whether these coagulation disturbances resolve with antiproteinuric therapy has yet to be studied. Methods: A total of 32 patients with overt proteinuria (median, 3.7 g day−1; interquartile range, 1.5–5.6) were enrolled in this intervention crossover trial designed to assess optimal antiproteinuric therapy with sodium restriction, losartan, and diuretics. Levels of various procoagulant and anticoagulant proteins, and parameters of two thrombin generation assays (calibrated automated thrombogram [CAT] and prothrombin fragment 1 + 2) were compared between the placebo period and the maximum antiproteinuric treatment period. As a secondary analysis, coagulation measurements of the placebo period in these patients were compared with those of 32 age‐matched and sex‐matched healthy controls. Results: Median proteinuria was significantly lower during the maximum treatment period (median, 0.9 g day−1; interquartile range, 0.6–1.4; P