Protein S deficiency occurs in the nephrotic syndrome.

Protein S activity may be compromised in patients with the nephrotic syndrome and contribute to a thrombotic diathesis. Protein S is found in two forms in plasma as free and functionally active protein S, and complexed to C4b-binding protein. When compared with controls, patients with nephrotic syndrome had reduced functional levels of protein S (69% +/- 27% [SD], p less than 0.001) despite having elevated levels of total protein S antigen (139% +/- 42%, p less than 0.001). Decreased protein S activity was caused by significant reductions in free (active) protein S levels (90% +/- 38%, p less than 0.05) due to the selective urinary loss of free protein S and elevation of C4b-binding protein levels (170% +/- 52%, p less than 0.001) that favors complex formation; and in the specific activity of the circulating free protein S (0.76; p less than 0.001). Along with this reduction in specific activity, we noted the abnormal electrophoretic mobility of the protein S in the presence of calcium ions. We conclude that acquired protein S deficiency occurs in the nephrotic syndrome and may be a risk factor for the development of the thromboembolic complications.