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 (>or=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.
Kronborg
Camilla S
CS
Department of Gynecology and Obstetrics, Randers County Hospital, Randers, Denmark. csk@mb.au.dk
Allen
Jim
J
Vittinghus
Erik
E
Knudsen
Ulla Breth
UB
D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D009961:Orosomucoid / Q000652:urine*; D011225:Pre-Eclampsia / Q000097:blood / Q000652:urine*; D011237:Predictive Value of Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D011446:Prospective Studies; D012709:Serum Albumin
D015415:Biomarkers; D009961:Orosomucoid; D012709:Serum Albumin; D003404:Creatinine