Urinary Angiotensinogen-Melatonin Ratio in Gestational Diabetes and Preeclampsia

Abstract

Background: A large research portfolio indicates that an activated renal renin-angiotensin system or a deficit on melatonin is associated with several cardiovascular pathologies. In this observational clinical study, we hypothesized that alterations in urinary melatonin or angiotensinogen levels may be altered in two common conditions, preeclampsia and gestational diabetes. Our study’s primary objective was to assess melatonin and angiotensinogen as novel disease biomarkers detectable and quantifiable in the urine of pregnant women with or without pregnancy complications.Methods: This was a concurrent cohort study of pregnant women with selected obstetric pathologies (gestational diabetes, preeclampsia, hypertension and obesity with hypertension). A group of healthy controls was also included. Urinary 6-sulfatoxymelatonin and angiotensinogen were measured by sensitive and specific ELISAs in first morning void urine samples. The patients were included in the cohort consecutively, and the diagnosis was blinded at the level of urine collection. Urinary 6-sulfatoxymelatonin and angiotensinogen levels were investigated in the patients included in the cohort.Results: Urinary levels of angiotensinogen were significantly higher in the gestational diabetes [angiotensinogen/creatinine ratio median (25th, 75th): 0.11 (0.07, 0.18)] and preeclampsia [0.08 (0.06, 0.18)] groups than in those with healthy pregnancy [0.05(0.04, 0.06]; 6-sulfatoxymelatonin levels were significantly lower in the gestational diabetes [ug/h: median (25th, 75th): 0.12(0.08, 0.17)] and preeclampsia [0.12 (0.09, 0.15)] groups than in those with healthy pregnancy [0.20 (0.15, 0.27]. Neither morning void protein/creatinine ratio nor 24-h urine protein estimate were significantly different between the study groups.Conclusion: These results suggest that urinary angiotensinogen levels may indicate an intrarenal RAS activation while melatonin production appears to be defective in gestational diabetes or hypertension. An angiotensinogen/melatonin ratio is suggested as an early biomarker for identification of gestational diabetes or hypertension. This report provides a basis for the potential use of melatonin for the treatment of preeclampsia. A prospective study in a larger number of patients to determine the operative characteristics of these markers as potential diagnostic tests is justified.

Multiplatform-Integrated Identification of Melatonin Targets for a Triad of Psychosocial-Sleep/Circadian-Cardiometabolic Disorders

“…Our research has demonstrated that the deep breathing test's heart rate variability is a reliable method for examining cardiac dysautonomia in conditions related to cardiovascular and psychosocial health [77][78][79]. Angiotensinogen in first-morning urine is associated with a decreased nocturnal melatonin secretion [80] and has been increased in chronic kidney disease [81], preeclampsia, and gestational diabetes [69].…”

“…Urinary 6-sulfatoxymelatonin (melatonin's metabolite) in the first-morning urine determines nighttime suppression of melatonin synthesis [65][66][67][68]. By measuring urinary 6-sulfatoximelatonin, we were able to identify preeclampsia, gestational diabetes [69], and social jetlag [70].…”

Maternal gestational diabetes mellitus and the childhood asthma in offspring: a meta-analysis

“…Interestingly, subgroup analysis also suggested that the association between maternal GDM and childhood asthma was weakened after adjustment of the prevalence maternal gestational hypertensive disorders. These findings may suggest that maternal GDM and gestational hypertensive disorders may share some similar mechanisms which may also be related to the pathogenesis of asthma in offspring, such as inflammatory response of interleukin balance [ 31 ] and hormonal changes involving the renin-angiotensin system [ 32 ].…”

Educational Review: The Impact of Perinatal Oxidative Stress on the Developing Kidney

“…Melatonin has been shown to regulate blood pressure and mitigate the development of hypertension in numerous animal models of renal programming ( 3 ). Recently, an increased urinary angiotensinogen/melatonin ratio was suggested to be an early biomarker for identification of gestational diabetes or pregnancy induced hypertension ( 136 ). In neonates, there is placental transfer of melatonin as endogenous melatonin production does not occur until 2–4 months of age and is known to be further delayed in preterm and FGR infants ( 134 ).…”