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.