Evaluation of Protein-Z and Antithrombin III Plasma Levels in Children with Minimal Change Nephrotic Syndrome

Background: In children with the nephrotic syndrome, acquired deficiency of anticoagulant proteins due to loss in the urine has been proposed as one of the major thrombogenic alterations. Low levels of protein Z, which is a single chain vitamin K-dependant glycoprotein synthesized by the liver, were reported to be a risk factor for increased incidence of thrombosis. Another biologic antagonist of coagulation is antithrombin III which has a relatively low molecular weight and expected to be lost in urine in patients with nephritic syndrome.
Objectives: Evaluation of both plasma protein Z levels, and antithrombin III activity as markers of thrombogenic disorders in children with minimal change nephrotic syndrome, and to elicit the relationship between their plasma levels in nephrotic children and different stages of the disease.
Methods: This study was carried out on 30 children with minimal change nephrotic syndrome with no thromboembolic manifestations. They were classified into 2 groups; group (I) included 15 children in the acute stage of nephrotic syndrome, and group (II) included 15 children in the remission stage of nephrotic syndrome under treatment with corticosteroids only. Fifteen healthy age and sex matched children were chosen as a control group; group 111.
Results: The mean plasma levels of both protein Z and of antithrombin III activity (%) in children with acute stage (group I) were significantly lower than those of children in remission (group II) and control group (group III) while there was no significant difference in these levels when group II was compared to group III. In group I, there was a significant positive correlation between protein Z and antithrombin III activity (%) (r-value = 0.83, p-value = 0.0001). Also, there were significant positive correlations between both parameters and total serum protein, serum albumin while there were significant negative correlations of both protein Z and antithrombin III to 24 hours protein in urine.
Conclusion: Even though there were no clinically detectable thromboembolic complications in the studied children with nephrotic syndrome, the plasma levels of protein Z and antithrombin III activity (%) were significantly decreased in children in the acute stage of the nephrotic syndrome, while those in the remission stage, plasma levels of protein Z and antithrombin III returned to normal values. Thus, children in the acute stage of nephrotic syndrome are still susceptible to thromboembolic complications and need close observation.