1. Pregnancy-associated changes in urinary uromodulin excretion in chronic hypertension.
- Author
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Mary S, Conti-Ramsden F, Boder P, Parveen H, Setjiadi D, Fleminger J, Brockbank A, Graham D, Bramham K, Chappell LC, and Delles C
- Subjects
- Adult, Animals, Female, Humans, Pregnancy, Rats, Antihypertensive Agents therapeutic use, Antihypertensive Agents pharmacology, Blood Pressure, Case-Control Studies, Chronic Disease, Creatinine urine, Disease Models, Animal, Hypertension, Pregnancy-Induced urine, Hypertension, Pregnancy-Induced physiopathology, Rats, Inbred SHR, Rats, Inbred WKY, Biomarkers urine, Hypertension urine, Hypertension physiopathology, Hypertension drug therapy, Uromodulin urine
- 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., (© 2024. The Author(s).)
- Published
- 2024
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