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Obstetric Nephrology and Immunology

Pregnancy Outcomes in Women with Renal Disease

Pregnancy in women with advanced chronic kidney disease, end-stage kidney disease requiring dialysis therapy or after renal transplantation is a challenging clinical scenario. These are high risk pregnancies with a high rate of maternal and fetal complications, even in women who have well-functioning kidney transplants. We are interested in better defining the maternal, obstetric and perinatal factors that affect these pregnancies, in order to improve outcomes for both mother and baby.

We are also investigating the long-term effects on babies of women and men with renal failure or women who are immunosuppressed during pregnancy.

The Immunology of Pregnancy and Pre-eclampsia

Pre-eclampsia is the leading medical complication of pregnancy, affecting 3-10% of pregnancies, causing significant maternal, fetal and neonatal morbidity.  It is a multi-system endothelial disorder, often associated with serious kidney dysfunction and renal pathology.   Pre-eclampsia also has long-lasting effects on well beyond the pregnancy, and is a marker for increased future risk of renal disease, albuminuria, hypertension, cardiovascular disease and mortality, and metabolic syndrome.  

Pregnancy is a unique state of immunological tolerance between mother and the fetus, not seen in any other stage of human life. The immunological process that occur in pregnancy are fascinating, and teach us a great deal about the function of the immune system. Pre-eclampsia is in part thought to be cause by a disruption of the normal immune responses to pregnancy, resulting in damage to the placenta and therefore the baby. Pre-eclampsia is associated with many pathways implicated in poor blood vessel development, poor oxygenation, loss of maternal-fetal immune tolerance and promotion of an inflammatory state. 

Dendritic cells are integral to the immune pathology of pre-eclampsia, due to their very critical role in promoting both immune tolerance and inducing strident adaptive immune responses.  Dendritic cells in the placenta are critical to placental formation  and are implicated as key regulators in pregnancy maintenance through their tolerance-promoting functions, leading to maternal acceptance the fetus. Disruption of this DC-mediated tolerance may be involved in pre-eclampsia pathogenesis. Altered dendritic cell numbers or phenotype, or aberrant DC function, may be central to the skewed immunological environment observed in pre-eclampsia. 

Further understanding of the role played by dendritic cells in normal pregnancy versus that seen in pre-eclampsia will give important insights into the pathogenesis of this common and often serious clinical problem. Through our collaboration with the Women's and Children's Hospital in Adelaide, we are investigating many aspects of dendritic cell function and their interaction with other immune cells in women with pregnancy and pre-eclampsia.