Responses of the renin-angiotensin-aldosterone system in pregnant chronic kidney disease patients with and without superimposed pre-eclampsia

Abstract

Background: Women with chronic kidney disease (CKD) are at increased risk of superimposed pre-eclampsia (SPE). Accurate identification of SPE is challenging. We hypothesized that specific components of the renin-angiotensin-aldosterone system (RAAS) would discriminate between CKD and SPE. The aim of the study was to establish differences in circulating and intrarenal RAAS in women with CKD with and without SPE and compare these to normotensive controls (NCs) and women with pre-eclampsia (PE).

Methods: White European NC women (n = 20), women with PE (n = 9), normotensive CKD without SPE (n = 8) and with SPE (n = 11) were recruited in the third trimester. Plasma renin, plasma and urine total angiotensinogen (AGT) concentrations were quantified by enzyme-linked immunosorbent assay, urinary tetrahydroaldosterone (TH-aldo) concentration by gas chromatography-mass spectrometry and placental growth factor (PlGF) by immunoassay.

Results: Urinary TH-aldo:creatinine ratios were lower in women with PE or SPE compared with NC or women with CKD (P < 0.05 for all). The same group differences were observed for plasma active renin and PlGF concentrations (P < 0.05 for all). Urine total AGT was higher in women with PE compared with NC (P < 0.05) and urine TH-aldo:urine AGT was lower (P < 0.05). However, women with SPE had lower urinary AGT concentrations compared with women with PE (P < 0.05). No differences in plasma total AGT were observed between groups.

Conclusions: Women with SPE have a lower urinary TH-aldo:creatinine ratio, lower plasma active renin and lower PlGF concentrations than women with CKD, comparable to women with PE without pre-existing disease, suggestive of similar pathophysiology. These data suggest disruption of the RAAS pathway in SPE similar to PE. Exploration of the predictive value of RAAS components for adverse pregnancy events in women with CKD is required.

Keywords: chronic kidney disease; hypertension in pregnancy; pre-eclampsia; renin-angiotensin-aldosterone system; urinary angiotensinogen.

FIGURE 1

Maternal (A) urinary aldosterone; (B) plasma active renin; (C) urinary AGT concentrations; and (D) plasma AGT concentrations in women with an NC pregnancy, PE pregnancy, CKD without SPE or CKD with SPE. Data represented as median (IQR) with outliers shown as symbols (filled circle); *P < 0.05.

FIGURE 2

Maternal plasma active PlGF concentration in women with a NC pregnancy, PE pregnancy, CKD without SPE or CKD with SPE. PlGF was measured in plasma samples from a previous larger study [22]. Data represented as median (IQR) with outliers shown by symbols; *P < 0.05; **P < 0.001; ***P < 0.0001.