Losartan and fetal toxic effects

Saji, Haruya; Yamanaka, Michiko; Hagiwara, Akiko; Ijiri, Rieko

doi:10.1016/s0140-6736(00)03648-5

Cited by 133 publications

(63 citation statements)

References 4 publications

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“…Similar morphologic lesions-the so-called "endocrine" kidney-have been described in a rat model of chronic renal hypoperfusion (45). Such lesions also are seen in anuric donor twins in twintwin transfusion syndrome (24,25), in the ipsilateral kidney in renal artery stenosis in children (10,30,46), and in fetuses that are exposed to ACE inhibitors or AT1 antagonists (31)(32)(33)(34). As observed by Marcussen (30) in renal artery stenosis, more proximal than distal tubules are destroyed by the ischemic process.…”

Section: Discussionmentioning

confidence: 64%

“…These situations include the twin-twin transfusion syndrome that is observed in monochorionic twin pregnancies in which the donor fetus presents RTD (23)(24)(25), major cardiac malformations (23,26), severe liver diseases (27)(28)(29), and fetal or infantile renal artery stenosis (30; personal observations). RTD with large fontanels also has been described in fetuses that are exposed in utero to angiotensin-converting enzyme (ACE) inhibitors (31,32) or angiotensin II (AngII) receptor antagonists (33,34). These observations of secondary, drug-induced RTD suggested that dysregulation of the renin-angiotensin system (RAS) could be responsible for the hereditary form of the disorder (17).…”

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confidence: 99%

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Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios

Lacoste

Cai

Guicharnaud

et al. 2006

Journal of the American Society of Nephrology

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Renal tubular dysgenesis is a clinical disorder that is observed in fetuses and characterized by the absence or poor development of proximal tubules, early onset and persistent oligohydramnios that leads to the Potter sequence, and skull ossification defects. It may be acquired during fetal development or inherited as an autosomal recessive disease. It was shown recently that autosomal recessive renal tubular dysgenesis is genetically heterogeneous and linked to mutations in the genes that encode components of the renin-angiotensin system. This study analyzed the clinical expression of the disease in 29 fetus/neonates from 18 unrelated families and evaluated changes in renal morphology and expression of the renin-angiotensin system. The disease was uniformly severe, with perinatal death in all cases as a result of persistent anuria and hypoxia related to pulmonary hypoplasia. Severe defects in proximal tubules were observed in all fetuses from 18 gestational weeks onward, and lesions also involved other tubular segments. They were associated with thickening of the renal arterial vasculature, from the arcuate to the afferent arteries. Renal renin expression was strikingly increased in 19 of 24 patients studied, from 13 families, whereas no renal renin was detected in four patients from three families. Angiotensinogen and angiotensinconverting enzyme were absent or present in only small amounts in the proximal tubule, in correlation with the severity of tubular abnormalities. No specific changes were detected in angiotensin II receptor expression. The severity and the early onset of the clinical and pathologic expression of the disease underline the major importance of this system in fetal kidney function and development in humans. The identification of the disease on the basis of precise histologic analysis and the research of the genetic defect now allow genetic counseling and early prenatal diagnosis. (1) in two stillborn siblings who had developed fetal anuria that resulted in oligohydramnios and the Potter phenotype. Fetal urine is the major constituent of amniotic fluid, especially after 18 to 20 gestational weeks, and estimation of its abundance is the best approach for evaluation of fetal kidney function. Oligohydramnios, whatever the cause, leads to fetal compression and decreased intrauterine motility, resulting in the Potter sequence that includes redundant skin, facial dysmorphia with large and flattened low-set ears, limb positioning

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Section: Discussionmentioning

confidence: 64%

mentioning

confidence: 99%

Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios

Lacoste

Cai

Guicharnaud

et al. 2006

Journal of the American Society of Nephrology

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“…On the contrary, Wallukat et al (16) reported that agonistic autoimmune antibody against AT1 was detected in the sera of pre-eclamptic women. These data show evidence of the deteriorative action of Ang II on the pathogenesis of pre-eclampsia; however, it has been difficult to elucidate the pathophysiological significance of aberrant RAS activation in the human case, because of the contraindication of RAS inhibition during pregnancy (24,25). Previously, using mice with PAH, we demonstrated the importance of RAS activation with enhanced AT1 signaling in the pathogenesis of hypertension during pregnancy (18,21).…”

Section: Discussionmentioning

confidence: 64%

Short-term suppression of the renin-angiotensin system in mice associated with hypertension during pregnancy

et al. 2012

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Abstract. Pregnancy-induced hypertension or pre-eclampsia is a major disorder that may result in serious complications for the mother and fetus. It is characterized from maternal hypertension in late pregnancy and peripheral tissue damage, including kidney, heart and placenta, and the fetus suffers from intrauterine growth retardation (IUGR) and high perinatal mortality. Recently, it has been postulated that angiotensin II (Ang II), a potent vasoconstrictor in the renin-angiotensin system (RAS), plays a pivotal role in the pathogenesis of pre-eclampsia; however, the beneficial effect of the suppression of RAS has not yet been fully elucidated. Previously, we generated a transgenic mouse model that developed pregnancyassociated hypertension (PAH) by the overproduction of Ang II in maternal circulation during late pregnancy. In addition, mice with PAH exhibited maternal and fetal abnormalities, such as proteinuria, cardiac hypertrophy, placental morphological changes and IUGR. In this study, in order to attenuate the activity of redundant RAS during the advanced stages of PAH, we administered olmesartan (Olm), an angiotensin receptor blocker, and captopril (Cp), an angiotensin converting enzyme inhibitor, from E17 to E19 days of gestation, and evaluated its effect on cardiac and placental abnormalities and fetal growth. Olm and Cp administration significantly lowered the blood pressure of mice with PAH, and placental histological change and severe IUGR were markedly ameliorated in both groups. On the contrary, Olm or Cp treatment had little effect on cardiac remodeling during the advanced stages of PAH. These findings highlight a variety of therapeutic actions of RAS repression on the progressive pathology of PAH in mice.

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“…[38,39] Similar anomalies have been reported with angiotensin II receptor blockers (ARBs). [40] ACE inhibitors and ARBs should be discontinued prior to conception, with appropriate birth control measures while on these agents.…”

Section: Drugs and The Kidneymentioning

confidence: 99%

Pregnancy and the kidneys

Wearne

2014

S Afr Med J

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Losartan and fetal toxic effects

Cited by 133 publications

References 4 publications

Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios

Renal Tubular Dysgenesis, a Not Uncommon Autosomal Recessive Disorder Leading to Oligohydramnios

Short-term suppression of the renin-angiotensin system in mice associated with hypertension during pregnancy

Pregnancy and the kidneys

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