Pregnancy-associated changes in urinary uromodulin excretion in chronic hypertension

被引:0
作者
Mary, Sheon [1 ]
Conti-Ramsden, Fran [2 ]
Boder, Philipp [1 ]
Parveen, Humaira [1 ]
Setjiadi, Dellaneira [1 ]
Fleminger, Jessica [2 ]
Brockbank, Anna [2 ]
Graham, Delyth [1 ]
Bramham, Kate [2 ]
Chappell, Lucy Charlotte [2 ]
Delles, Christian [1 ]
机构
[1] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Sch Cardiovasc & Metab Hlth, 126 Univ Pl, Glasgow G12 8TA, Scotland
[2] Kings Coll London, Dept Women & Childrens Hlth, London, England
关键词
Chronic hypertensive pregnancy; Kidney physiology; Uromodulin; Blood pressure; BODY-MASS INDEX; CHRONIC KIDNEY-DISEASE; APOL1 RISK VARIANTS; RENAL HEMODYNAMICS; BLOOD-PRESSURE; DAMAGE; OBESITY; PREECLAMPSIA; PHYSIOLOGY; WOMEN;
D O I
10.1007/s40620-023-01830-6
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
BackgroundPregnancy 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.MethodsUrinary 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).ResultsIn 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.ConclusionsIn 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.
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页码:597 / 610
页数:14
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