Evidence of augmented intrarenal angiotensinogen associated with glomerular swelling in gestational hypertension and pre-eclampsia: clinical implications

Mistry, Hiten D.; Kurlak, Lesia O.; Gardner, David S.; Torffvit, Ole; Hansen, Alastair; Broughton Pipkin, Fiona; Strevens, Helena

Abstract

Background-—AGT (angiotensinogen) synthesis occurs in renal proximal tubular epithelial cells, independent from systemic AGT, as a component of the intrarenal renin–angiotensin system. We investigated urinary AGT, as a biomarker for renin–angiotensin system activation, and electrolyte concentrations, in relation to glomerular volume, as a proxy for glomerular endotheliosis in renal biopsy tissue from pregnant normotensive control and hypertensive women.

Methods and Results-—Urine samples were collected from normotensive control (n=10), gestational hypertensive (n=6), and preeclamptic (n=16) women at the time a renal biopsy was obtained. Samples were collected from Lund University Hospital between November 1999 and June 2001. Urinary AGT, potassium, and sodium were measured, normalized to urinary creatinine. Mean glomerular volume was estimated from biopsy sections. AGT protein expression and localization were assessed in renal biopsies by immunohistochemistry. Urinary AGT concentrations were higher in hypertensive pregnancies (median, gestational hypertension: 11.3 ng/mmol [interquartile range: 2.8–13.6]; preeclampsia: 8.4 ng/mmol [interquartile range: 4.2–29.1]; normotensive control: 0.6 ng/mmol [interquartile range: 0.4–0.8]; P [less than] 0.0001) and showed a positive relationship with estimated mean glomerular volume. Urinary potassium strongly correlated with urinary AGT (P [less than] 0.0001). Although numbers were small, AGT protein was found in both glomeruli and proximal tubules in normotensive control but was present only in proximal tubules in women with hypertensive pregnancy.

Conclusions-—This study shows that pregnant women with gestational hypertension or preeclampsia have increased urinary AGT and potassium excretion associated with signs of glomerular swelling. Our data suggest that the kidneys of women with hypertensive pregnancies and endotheliosis have inappropriate intrarenal renin–angiotensin system activation, which may contribute toward the pathogenesis of hypertension and renal injury.

Citation

Mistry, H. D., Kurlak, L. O., Gardner, D. S., Torffvit, O., Hansen, A., Broughton Pipkin, F., & Strevens, H. (2019). Evidence of augmented intrarenal angiotensinogen associated with glomerular swelling in gestational hypertension and pre-eclampsia: clinical implications. Journal of the American Heart Association, 8(13), 1-11. https://doi.org/10.1161/JAHA.119.012611

• Journal Article Type: Article
• Acceptance Date: May 17, 2019
• Online Publication Date: Jul 2, 2019
• Publication Date: Jul 2, 2019
• Deposit Date: Jun 6, 2019
• Publicly Available Date: Jun 28, 2019
• Journal: Journal of the American Heart Association
• Electronic ISSN: 2047-9980
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 13
• Article Number: e012611
• Pages: 1-11
• DOI: https://doi.org/10.1161/JAHA.119.012611
• Keywords: Kidney; Pregnancy; Hypertension; Urine; Angiotensinogen; Glomerular
• Public URL: https://nottingham-repository.worktribe.com/output/2149679
• Publisher URL: https://www.ahajournals.org/doi/10.1161/JAHA.119.012611
• Contract Date: Jun 6, 2019