Is urinary excretion of plasminogen associated with development of pre-eclampsia? An observational, explorative case-control study

Abstract

Objectives Pre-eclampsia (PE) is characterised by renal glomerular endotheliosis and injury to the glomerular filtration barrier with proteinuria. Patients with PE display aberrant filtration of the plasma proenzyme plasminogen which is activated, in the tubular fluid, to plasmin. Plasmin may activate the epithelial sodium channel and cause impaired sodium excretion and contribute to hypertension. An explorative study was conducted to test the association between urinary total plasminogen/plasmin and the development of PE. A positive association was hypothesised. Design An observational, explorative, nested case-control study of healthy pregnant women. Settings A Danish County hospital. Samples were collected between 2001 and 2004. Participants 1631 healthy pregnant women participated. Urine samples were collected longitudinally six times during pregnancy. 30 developed PE (cases) and were compared with 146 randomly selected healthy pregnant women (controls). Primary outcome The association between total plasminogen/plasmin excreted in the urine and PE development is expressed by ORs. Total urinary excretion of plasminogen/plasmin was defined by the urine plasminogen-plasmin/creatinine ratio. Secondary outcome The association between urine (u)-albumin/creatinine ratio, u-aldosterone/creatinine ratio and PE development is expressed by ORs. The correlation between urinary (u-) plasmin and u-aldosterone concentration is expressed as a correlation coefficient. Results The development of PE in late pregnancy was associated with increased levels of the urine plasminogen-plasmin/creatinine ratio (OR=2.35; 95% CI: 1.12 to 4.93; p<0.05). U-aldosterone/creatinine ratio did not predict PE at any time. U-albumin/creatinine ratio was positively associated with the development of PE from gestational week 33 (OR=14.04; 95% CI: 2.56 to 76.97; p<0.01) and in week 33-35 (OR=14.15; 95% CI: 3.44 to 58.09; p<0.001) and after gestational week 36, respectively. Conclusion Aberrant filtration of plasminogen may contribute to the pathophysiological features of impaired sodium excretion and hypertension associated with PE late in pregnancy. However, increased urinary albumin levels reveal stronger associations with PE development compared with urinary plasminogen levels.