Pre-symptomatic increase in urine-orosomucoid excretion in pre-eclamptic women

Background. Although the pre-eclamptic pathogenesis begins at least around the 18th week of pregnancy, clinically evident disease often does not appear until the third trimester. This long pre-symptomatic latency period has led to intensive research for early markers of evolving disease. We evaluated urine excretion and plasma levels of orosomucoid and albumin longitudinally in healthy and pre-eclamptic pregnancies. Orosomucoid is an acute phase protein involved in inflammation and protection of the endothelium. Methods. From a prospective, longitudinal cohort study consisting of 1,631 women, 32 women developed pre-eclampsia, and 5 controls for every case of pre-eclampsia were found. Blood samples were collected 4 times and urine samples 6 times from the 18/19th week and throughout pregnancy. Orosomucoid and albumin in plasma were analysed by standard methods, and in urine by sandwich ELISA. Results. Orosomucoid/creatinin excretion ratio was significantly higher early in pre-eclamptic pregnancies ( from the 20th week of pregnancy, p = 0.0053) compared with healthy pregnancies, the difference increased throughout pregnancy. Albumin/creatinin ratio increased subsequent to the increase in orosomucoid. In the plasma samples, orosomucoid was significantly higher late in pre-eclamptic pregnancies (>= 36th week, p = 0.0275). Conclusions. Pre-eclampsia is associated with a pre-symptomatic increase in the urine excretion of orosomucoid, and orosomucoid excretion precedes that of albumin. Orosomucoid excretion can probably be used as a prognostic tool in combination with other screening methods, and seems to be a more sensitive marker for evolving pre-eclampsia than albumin. Plasma orosomucoid is significantly increased late in pre-eclampsia. Thus, the increased excretion of orosomucoid must primarily originate from altered renal processing of orosomucoid.