Understanding the link between kidney health and pregnancy outcomes

Reproductive health is important to a woman's overall health and well-being and is increasingly recognised as a sex specific marker for diseases in later life. Women who experience complications of pregnancy, such as pre-eclampsia, are more likely to have heart disease in later life for example. However, there are gaps in our knowledge about whether women who experience complications of pregnancy are more likely to experience reduced kidney function and kidney disease in later life. I will use information from several studies, including large datasets of routinely collected clinical data and smaller studies with detailed measurements, to examine if women who experience different complications in pregnancy are at greater risk of reduced kidney function and kidney disease in later life. Understanding the relationship between women's reproductive health and later disease is important as it may identify the need for increased monitoring of kidney function after pregnancy, crucially as some of the causes of kidney disease are preventable. Women at high risk can then be offered advice or treatment that will lower that risk.

There are also gaps in knowledge about whether women who have reduced kidney function prior to pregnancy are at greater risk of developing pregnancy complications. Here, I will measure kidney function prior to pregnancy, in early pregnancy, and throughout pregnancy, to examine if women with reduced kidney function are at greater risk of pregnancy complications such as pre-eclampsia and diabetes in pregnancy. This is important as women are increasingly having children at older ages, and it is vital that we understand what affects women's chances of having a healthy pregnancy.

Finally, if kidney function needs to be tested in pregnancy, a substance in the blood called creatinine is measured. However, there is no clear guidance on acceptable levels in pregnancy. I will use multiple studies to address this knowledge gap and with the aim of establishing the normal/acceptable range. I will also examine an alternative measures of kidney function, cystatin C. Unlike creatinine, cystatin C is produced from all cells in the body, rather than just muscles, and so isn't affected by things like muscle mass. The work will provide insights into how women should be managed if changes in creatinine are observed during pregnancy.

Reproductive and obstetric health are important to a woman's overall health and increasingly recognised as a sex specific predictor of chronic disease in later life. Adverse pregnancy outcomes (APOs), including pre-eclampsia, gestational hypertension, gestational diabetes and preterm delivery are associated with greater future cardiovascular disease. Compared to cardiovascular outcomes, relatively little is known about the long-term risk of chronic kidney disease (CKD) in women who have experienced APOs. I will use data from multiple cohort studies and electronic health record data to investigate if APOs are associated with reduced kidney function and CKD risk later in life.

I will also compare trajectories of kidney function of women with and without APOs, from before to after pregnancy. This will help establish whether differences in kidney health already exist before pregnancy or emerge post-pregnancy. The risk of some APOs is increased in women with CKD. However, less is known about the risk of APOs in women with moderate or slight kidney impairment; I will examine this in prospective cohort studies. Furthermore, I will use Mendelian randomisation (MR) analyses to establish if any observed relationships are causal.

Serum creatinine concentration is recommended for assessing kidney function in pregnancy, but a normal range has not been established. I will use using new data and systematic review techniques to calculate a reference range for creatinine in pregnancy. I will also assess whether cystatin C could be a useful blood marker of kidney function in pregnancy, which could give insights into how women should be managed if changes in creatinine are observed during pregnancy. This work has the potential to inform preventive strategies, for APOs, and for CKD in later life. This is important because CKD is preventable and has a better prognosis if treated earlier, and is costly to health services, especially if it develops into end-stage kidney disease.