The intrarenal renin angiotensin system in pregnancy and its potential in predicting pregnancy outcome and renal dysfunction in Indigenous and non-Indigenous Australian women (#102)

Kirsty G Pringle 1 2 Shane D Sykes 1 2 Loretta Weatherall 1 3 Mohamed Galal 1 Don Clausen 4 Roger Smith 1 Kym Rae 1 3 Eugenie R Lumbers 1 2
  1. Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, Australia
  2. School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia
  3. Gomeroi Gaaynggal Centre, Tamworth, NSW
  4. Pathology New England, Tamworth, NSW

Background: Indigenous Australian women are 2.5 times more likely to get preeclampsia in pregnancy, possibly because of a high incidence of undetected renal disease. We proposed that the intrarenal renin angiotensin system (iRAS) is activated in normal pregnancy and that failure to activate the iRAS may predispose to preeclampsia.

Methods: Urinary angiotensinogen/creatinine (uAGT/creat), albumin/creat, and protein/creat were measured in 10 non-pregnant and 17 pregnant non-Indigenous women and in 61 Indigenous pregnant women recruited in Tamworth and Newcastle as part of the Gomeroi gaaynggal ArtsHealth program. In Indigenous pregnant women, uACE/creat, uprorenin/creat and uactive renin/creat were also measured.

Results: uAGT/creat was higher in pregnant (18.2 ± 3.2 ug/mmol) compared to non-pregnant women (1.1 ± 0.3 ug/mmol, P=0.001) but women with clinical proteinuria and/or preeclampsia had low uAGT/creat (n=3). Hypertensive women had normal high uAGT/creats (n=4).

Indigenous pregnant women had lower uAGT/creat (2.9 ± 1.0 ug/mmol, P=0.01) than non-Indigenous pregnant women but their urinary protein/creat and albumin/creats were not significantly different. Two groups of Indigenous women were identified, those with a uAGT/creat <2ug/mmol (n=37) and those with a value >2.0ug/mmol (n=12). Only the low uAGT/creat Indigenous pregnant women showed significant correlations between uAGT/creat and albumin/creat (rho=0.367, P=0.027), uactive renin/creat and both urinary albumin/creat (rho=0.493, P=0.002) and urinary protein/creat (rho=0.603, P<0.001, n=36). uAGT/creat fell with gestation (rho= -0.329, P=0.047) as did GFR (increased Cystatin C, rho=0.592, P<0.001, n=36), which was  correlated with uprotein/creat  (rho =0.357, P=0.03, n=36). Only in women with a normal high uAGT/creat was uNa/K inversely related to gestation age (rho=-0.456, P=0.05, n=18).

Conclusion: The iRAS is activated in normal pregnancy. This is not the case in women with proteinuria/preeclampsia or in many Indigenous women. Therefore a low uAGT/creat in pregnancy may indicate impaired renal function and be associated with an increased risk of preeclampsia.

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