Changes in renal tubular sodium transporters
detected in urinary exosomes in pre-eclampsia
Chih-Chiang
Hu3,4, Marina Katerelos4, Suet-Wan Choy1,2,3,4,
Amy Crosthwaite2,3, Peter Mount1,3,4, Natasha Cook1,3,4,
Kathy Paizis1,2, David A. Power1,3,4
1Department of Nephrology, Austin Health,
Heidelberg, Vic., Australia;
2Mercy Hospital for Women, Heidelberg, Vic., Australia
3University of Melbourne, Parkville, Vic., Australia;
4Kidney Laboratory, Austin Health, Heidelberg, Vic., Australia
Background: In pre-eclampsia, the suppressed
renin-angiotensin-aldosterone system and aberrant renal sodium retention
contribute to the development of hypertension (Verdonk et al., 2014). Limited studies have examined the role of renal
tubular salt transporters (bumetanide-sensitive cotransporter NKCC2,
thiazide-sensitive cotransporter NCC, epithelial sodium channel ENaC) in the
pathogenesis of pre-eclampsia. Urinary exosomes provide a non-invasive
technique in describing the in vivo
changes in renal tubular sodium transporter activity (Pisitkun et al., 2004).
Aim: To characterise the phosphorylation and expression of tubular sodium
transporters, detectable in urinary exosomes, in pre-eclamptic, normotensive
pregnant and normotensive non-pregnant females.
Methods: A cross-sectional study of pre-eclamptic, normotensive pregnant patients
and non-pregnant female controls was conducted. Urinary exosomal content of
sodium transporters, isolated by ultracentrifugation, was analysed by Western
Blot.
Results: A significant increase in phosphorylation of S130 residue on NKCC2 was
observed in pre-eclamptic patients (n=8) compared to normotensive pregnancy
(n=18, p=0.0013). However, phosphorylation of T105 residue (p=0.0042) of NKCC2
and T60 residue (p=0.0092) on NCC were significantly reduced in pre-eclampsia
(n=8) compared to normotensive pregnancy (n=18). There was also a significant
increase in alpha (p=0.0111) and gamma (p=0.0229) subunits of ENaC in pre-eclamptic
patients (n=8) compared to normotensive pregnancy (n=9).
Study groups
|
Pre-eclampsia (n=8)
|
Normotensive
pregnant (n=18)
|
Non-pregnant
control (n=19)
|
Maternal Age (y)
|
33.5±4.5
|
33.3±3.6
|
25.1±1.3
|
Gestation (week)
|
33.0±3.3
|
32.8±3.5
|
n/a
|
Primiparous (%)
|
75%
|
22.2%
|
n/a
|
SBP (mmHg)
|
155.5±4.2
|
115.2±9.5
|
104.3±10.5
|
DBP (mmHg)
|
96.5±8.0
|
69.2±9.0
|
69.0±8.0
|
BMI (kg/m2)
|
29.6±10.7
|
28.4±5.0
|
20.5±1.9
|
Conclusions:In pre-eclampsia, there were
increased ENaC expression and phosphorylation of NKCC2 at S130 while
phosphorylation of T105 and T60 were reduced in NKCC2 and NCC respectively.
This data suggests increased activity of ENaC and the NKCC2 transporters.
Although the observed findings were exploratory, it suggests existence of novel
activation pathways affecting salt transport in pre-eclampsia that require
future research and may provide a potential early non-invasive biomarker for
pre-eclampsia.