Mary, S. et al. (2024) Pregnancy-associated changes in urinary uromodulin excretion in chronic hypertension. Journal of Nephrology, (doi: 10.1007/s40620-023-01830-6) (PMID:38236469) (Early Online Publication)
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Abstract
Background: Pregnancy involves major adaptations in renal haemodynamics, tubular, and endocrine functions. Hypertensive disorders of pregnancy are a leading cause of maternal mortality and morbidity. Uromodulin is a nephron-derived protein that is associated with hypertension and kidney diseases. Here we study the role of urinary uromodulin excretion in hypertensive pregnancy. Methods: Urinary uromodulin was measured by ELISA in 146 pregnant women with treated chronic hypertension (n = 118) and controls (n = 28). We studied non-pregnant and pregnant Wistar Kyoto and Stroke Prone Spontaneously Hypertensive rats (n = 8/strain), among which a group of pregnant Stroke–Prone Spontaneously Hypertensive rats was treated with either nifedipine (n = 7) or propranolol (n = 8). Results: In pregnant women, diagnosis of chronic hypertension, increased maternal body mass index, Black maternal ethnicity and elevated systolic blood pressure at the first antenatal visit were significantly associated with a lower urinary uromodulin-to-creatinine ratio. In rodents, pre-pregnancy urinary uromodulin excretion was twofold lower in Stroke-Prone Spontaneously Hypertensive rats than in Wistar Kyoto rats. During pregnancy, the urinary uromodulin excretion rate gradually decreased in Wistar Kyoto rats (a twofold decrease), whereas a 1.5-fold increase was observed in Stroke-Prone Spontaneously Hypertensive rats compared to pre-pregnancy levels. Changes in uromodulin were attributed by kidney injury in pregnant rats. Neither antihypertensive changed urinary uromodulin excretion rate in pregnant Stroke-Prone Spontaneously Hypertensive rats. Conclusions: In summary, we demonstrate pregnancy-associated differences in urinary uromodulin: creatinine ratio and uromodulin excretion rate between chronic hypertensive and normotensive pregnancies. Further research is needed to fully understand uromodulin physiology in human pregnancy and establish uromodulin’s potential as a biomarker for renal adaptation and renal function in pregnancy.
| Item Type: | Articles |
|---|---|
| Additional Information: | This work was supported by the Academy of Medical Sciences and Royal Society Newton International Fellowship [grant number NIF004\1010 (SM)]; the British Heart Foundation Centre of Research Excellence Award [grant numbers RE/18/6/34217 (CD)]; the Wellcome Trust [grant number 221774/Z/20/Z (CD)]; a British Heart Foundation PhD Fellowship [grant numbers FS/18/58/34179 (PB)]. FCR is supported by the Medical Research Council [grant number MR/V006835/1]. LCC is supported by an NIHR Senior Investigator award. |
| Keywords: | Chronic hypertensive pregnancy, kidney physiology, uromodulin, blood pressure. |
| Status: | Early Online Publication |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Setjiadi, Ms Dellaneira and Parveen, Humaira and Boder, Philipp and Samji, Dr Sheon and Delles, Professor Christian and Graham, Dr Delyth |
| Creator Roles: | Samji, S.Conceptualization, Methodology, Formal analysis, Investigation, Writing – original draft, Writing – review and editing, Funding acquisition, Supervision Boder, P.Methodology Parveen, H.Methodology, Writing – review and editing Graham, D.Methodology, Writing – review and editing Delles, C.Conceptualization, Writing – original draft, Writing – review and editing, Funding acquisition, Supervision |
| Authors: | Mary, S., Conti-Ramsden, F., Boder, P., Parveen, H., Setjiadi, D., Fleminger, J., Brockbank, A., Graham, D., Bramham, K., Chappell, L. C., and Delles, C. |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Journal of Nephrology |
| Publisher: | Springer |
| ISSN: | 1121-8428 |
| ISSN (Online): | 1724-6059 |
| Published Online: | 18 January 2024 |
| Copyright Holders: | Copyright: © The Author(s) 2024 |
| First Published: | First published in Journal of Nephrology 2024 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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