The Predictive Power of Proteinuria in Pregnancy

Background- This thesis examines the power of urinary protein excretion – both quantitative and qualitative – during pregnancy in predicting maternal and fetal outcomes. The independent effect of proteinuria in predicting adverse outcomes for women with chronic kidney disease (CKD) has not been well characterised. Secondly, pre‐eclampsia is a leading cause of maternal and fetal morbidity and mortality worldwide. There are no tests to predict pre‐eclampsia in clinical use. Methods- Analysis of prospective data collected from pregnant women with CKD from multiple centres in the United Kingdom. A longitudinal prospective clinical study of urine proteomics in early pregnancy in women at high risk of pre‐eclampsia to identify putative predictive biomarkers. Results- Data was analysed from 313 pregnancies in 256 women with CKD from 2005 to 2010. Urine ACR or PCR is accurate in quantifying proteinuria in women with CKD during pregnancy. Women in whom pregnancy‐associated increases in proteinuria failed to return to baseline have increased progression of renal dysfunction compared to other women. Proteinuria at conception is not independently associated with pregnancy-associated accelerated loss of renal function but does predict preterm delivery. Nephrotic syndrome in pregnancy is not independently associated with adverse fetal outcomes. 145 participants were enrolled in a study of urine proteomics of whom 11 developed pre‐eclampsia. A panel of 5 peptides was identified in urine collected prior to 20 weeks gestation that predicted the subsequent development of pre‐eclampsia with 92% accuracy. A further peak was indentified in specimens collected from 20 to 25 weeks gestation with similar predictive performance. Summary- Maternal proteinuria at conception is associated with preterm delivery in women with CKD. Increased proteinuria that fails to resolve postpartum is associated with a more rapid decline. Accurate prediction of the development of pre‐eclampsia in women at high risk was achieved from urine proteomic analysis prior to 20 weeks gestation.