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Evidence of Augmented Intrarenal Angiotensinogen Associated With Glomerular Swelling in Gestational Hypertension and Preeclampsia: Clinical Implications.
J Am Heart Assoc 2019; 8(13):e012611JA

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 pre-eclamptic (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<0.0001) and showed a positive relationship with estimated mean glomerular volume. Urinary potassium strongly correlated with urinary AGT (P<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.

Authors+Show Affiliations

1 Division of Child Health, Obstetrics & Gynaecology School of Medicine University of Nottingham United Kingdom.1 Division of Child Health, Obstetrics & Gynaecology School of Medicine University of Nottingham United Kingdom.2 School of Veterinary Medicine and Science University of Nottingham United Kingdom.3 Primary Care Unit Lindsdal, Kalmar Sweden.4 Department of Pathology Herlev University Hospital Herlev Denmark.1 Division of Child Health, Obstetrics & Gynaecology School of Medicine University of Nottingham United Kingdom.5 Department of Obstetrics Skåne University Hospital Lund University Lund Sweden.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31237175

Citation

Mistry, Hiten D., et al. "Evidence of Augmented Intrarenal Angiotensinogen Associated With Glomerular Swelling in Gestational Hypertension and Preeclampsia: Clinical Implications." Journal of the American Heart Association, vol. 8, no. 13, 2019, pp. e012611.
Mistry HD, Kurlak LO, Gardner DS, et al. Evidence of Augmented Intrarenal Angiotensinogen Associated With Glomerular Swelling in Gestational Hypertension and Preeclampsia: Clinical Implications. J Am Heart Assoc. 2019;8(13):e012611.
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 Preeclampsia: Clinical Implications. Journal of the American Heart Association, 8(13), pp. e012611. doi:10.1161/JAHA.119.012611.
Mistry HD, et al. Evidence of Augmented Intrarenal Angiotensinogen Associated With Glomerular Swelling in Gestational Hypertension and Preeclampsia: Clinical Implications. J Am Heart Assoc. 2019 Jul 2;8(13):e012611. PubMed PMID: 31237175.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence of Augmented Intrarenal Angiotensinogen Associated With Glomerular Swelling in Gestational Hypertension and Preeclampsia: Clinical Implications. AU - Mistry,Hiten D, AU - Kurlak,Lesia O, AU - Gardner,David S, AU - Torffvit,Ole, AU - Hansen,Alastair, AU - Broughton Pipkin,Fiona, AU - Strevens,Helena, Y1 - 2019/06/25/ PY - 2019/6/26/entrez PY - 2019/6/27/pubmed PY - 2019/6/27/medline KW - angiotensinogen KW - glomerular KW - hypertension KW - kidney KW - pregnancy KW - urine SP - e012611 EP - e012611 JF - Journal of the American Heart Association JO - J Am Heart Assoc VL - 8 IS - 13 N2 - 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 pre-eclamptic (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<0.0001) and showed a positive relationship with estimated mean glomerular volume. Urinary potassium strongly correlated with urinary AGT (P<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. SN - 2047-9980 UR - https://www.unboundmedicine.com/medline/citation/31237175/Evidence_of_Augmented_Intrarenal_Angiotensinogen_Associated_With_Glomerular_Swelling_in_Gestational_Hypertension_and_Preeclampsia:_Clinical_Implications L2 - http://www.ahajournals.org/doi/full/10.1161/JAHA.119.012611?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -