Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present the case of a child who died of pulmonary hypoplasia as a result of the oligohydramnios sequence. The mother was taking enalapril, as well as propranolol and hydrochlorothiazide, for treatment of hypertension associated with systemic lupus erythematosus. Autopsy examination revealed severe renal tubular malformation. Correlation of animal data with previous case reports of neonatal anuria in association with maternal angiotensin converting enzyme inhibitors suggests that these agents may have a deleterious effect on fetal renal development and general well-being.
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PMID:Oligohydramnios sequence and renal tubular malformation associated with maternal enalapril use. 230 91

A female neonate, born by cesarean section at 37 weeks of gestation, presented with respiratory distress syndrome, right pneumothorax and anuria. A sonogram showed increased echogenicity, with neither hydronephrosis nor macroscopic cysts. Peritoneal dialysis was started on the 14th day because of renal insufficiency, but the newborn died on the 33rd day. Family history was unremarkable, except that the mother received piroxicam at about the 26th week of gestation. A sonogram at the 28th week showed oligohydramnios. Histopathological study of the kidneys revealed crowded glomeruli and only few differentiated proximal convoluted tubules in the inner cortex, abnormally differentiated microcystic tubules and microcystic glomeruli in the outer cortex. Periodic acid-Schiff staining showed only traces of brush border in the dilated tubules of the outer cortex. Immunoperoxidase staining for epithelial membrane antigen was positive in the luminal border of all tubules. Electron microscopy confirmed the presence of brush border remnants and other proximal tubular characteristics in some segments. The renal abnormality bears some similarities to that found in familiar renal tubular dysgenesis, but it fits better with those described after maternal use of angiotensin converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs. The lesion in this case appears to have resulted from fetal exposure to piroxicam. Recently, a second pregnancy ended in a completely normal female newborn.
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PMID:Fetal renal maldevelopment with oligohydramnios following maternal use of piroxicam. 781 9

To find out which of the effects of angiotensin converting enzyme (ACE) inhibitors on the fetus are due to their actions in the mother and which are direct effects due to blockade of the fetal renin-angiotensin system, enalapril (150 mg twice daily i.v.), which does not readily cross the sheep placenta, was given for 3 days to nine chronically catheterized pregnant ewes, 5 days after fetal urine and lung liquid had been continuously drained and while drainage of these fetal fluids continued. Drainage of fetal fluids was carried out so that a net sodium deficit would be incurred, and the dependency of the ewe on the activity of her renin-angiotensin system (RAS) for maintenance of her arterial pressure and fluid and electrolyte balance would be increased. During drainage of fetal fluids ewes drank more and increased their net water balance (p < 0.025). With enalapril, ewes became hypotensive (p < 0.005), but heart rate did not change. Maternal plasma potassium (K) levels increased (p < 0.05) and the plasma sodium to potassium ratio (Na:K) decreased (p < 0.005). Enalapril did not reduce maternal water intake nor change her urine output. After 5 days of drainage, fetal plasma K levels (p < 0.05) were higher and plasma Na:K (p < 0.025) was lower. After maternal enalapril, lung liquid flow and electrolyte excretion were transiently reduced (p < 0.05). Fetal plasma K levels increased further (p < 0.025) and plasma Na:K ratio decreased (p < 0.025 - p < 0.01). Fetal arterial PO2 was reduced 2 h after enalapril (p < 0.005) and was low on the last 2 days of treatment. Although fetal fractional reabsorption of K fell (p < 0.01) by the last day of enalapril treatment, the increase in fetal K excretion was not significant, because by this time sufficient enalapril was present in the fetal circulation to reduce glomerular filtration rate (GFR, p < 0.025 - p < 0.001). It is concluded that the toxicity of ACE inhibitors may be related to those effects in the ewe that lead to reduced fetal arterial oxygen levels and increased fetal plasma K levels. In the latter case it is postulated that inhibition of the maternal RAS may leave ewe and fetus deficient in aldosterone, leading to the rise in K levels. Thus the toxic effects of ACE inhibitors can be mediated through their effects on the mother, but their ability to cause fetal renal failure and oligohydramnios is due to their direct effects on the fetal RAS.
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PMID:Effects of inhibition of the maternal renin-angiotensin system on maternal and fetal responses to drainage of fetal fluids. 896 Mar 88

Autosomal recessive renal tubular dysgenesis is a severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (Potter phenotype). Absence or paucity of differentiated proximal tubules is the histopathological hallmark of the disease and may be associated with skull ossification defects. We studied 11 individuals with renal tubular dysgenesis, belonging to nine families, and found that they had homozygous or compound heterozygous mutations in the genes encoding renin, angiotensinogen, angiotensin converting enzyme or angiotensin II receptor type 1. We propose that renal lesions and early anuria result from chronic low perfusion pressure of the fetal kidney, a consequence of renin-angiotensin system inactivity. This is the first identification to our knowledge of a renal mendelian disorder linked to genetic defects in the renin-angiotensin system, highlighting the crucial role of the renin-angiotensin system in human kidney development.
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PMID:Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. 1611 25

The renin-angiotensin system plays an important role in the regulation of blood pressure. The use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers both control hypertension by interruption of the production or action of angiotensin II, the major end-product of the renin-angiotensin system. The use of angiotensin converting enzyme inhibitors in pregnant women revealed serious and deleterious effects on fetal development including renal failure, renal dysplasia, hypotension, oligohydramnios, pulmonary hypoplasia, and hypocalvaria. The fetal effects of angiotensin converting enzyme inhibitors seem to be greatest during the 2nd and 3rd trimesters of pregnancy. The fetal effect of angiotensin converting enzyme inhibitors during the 1st trimester is controversial. These effects may represent the effect of hypoperfusion in the fetus and not a teratogenic effect. The effect of angiotensin receptor blockers is similar to converting enzyme inhibitors. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers should be avoided in all pregnant women. Alternative antihypertensive medications should be considered for use in women of childbearing years.
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PMID:Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. 1642 19

The number of pregnant women and women of childbearing age who are receiving drugs is increasing. A variety of drugs are prescribed for either complications of pregnancy or maternal diseases that existed prior to the pregnancy. Such drugs cross the placental barrier, enter the fetal circulation and potentially alter fetal development, particularly the development of the kidneys. Increased incidences of intrauterine growth retardation and adverse renal effects have been reported. The fetus and the newborn infant may thus experience renal failure, varying from transient oligohydramnios to severe neonatal renal insufficiency leading to death. Such adverse effects may particularly occur when fetuses are exposed to NSAIDs, ACE inhibitors and specific angiotensin II receptor type 1 antagonists. In addition to functional adverse effects, in utero exposure to drugs may affect renal structure itself and produce renal congenital abnormalities, including cystic dysplasia, tubular dysgenesis, ischaemic damage and a reduced nephron number. Experimental studies raise the question of potential long-term adverse effects, including renal dysfunction and arterial hypertension in adulthood. Although neonatal data for many drugs are reassuring, such findings stress the importance of long-term follow-up of infants exposed in utero to certain drugs that have been administered to the mother.
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PMID:Effects of maternally administered drugs on the fetal and neonatal kidney. 1668 56

Autosomal recessive renal tubular dysgenesis (RTD) is a clinical disorder observed in fetuses, characterized by absence or poor development of proximal tubules and early onset and persistent oligohydramnios leading to the Potter sequence, associated with skull ossification defect. The disease is uniformly severe resulting in low blood pressure and perinatal death in most cases or in chronic renal disease in the few surviving patients. Based on the phenotype and the finding of striking changes in renal renin expression (absent or massive), we hypothesized and demonstrated that genetic defects in the renin-angiotensin system (RAS) components are the underlying causes of the disease. At the present time, molecular screening has been performed in 46 families (F) and homozygous or compound heterozygous mutations have been detected in 41. They affect the genes encoding renine (9F), angiotensinogen (3F), AT1 receptor (3F) and angiotensin converting enzyme (26F). These findings highlight the importance of the RAS during human kidney development. Moreover, the identification of the disease based on precise histological and immunohistological analysis, and the research of the genetic defect, now allow genetic counseling and early prenatal diagnosis.
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PMID:[Mutations in renin-angiotensin system genes and kidney developmental anomalies]. 2012 89

We report a male newborn presenting with sonographically normal kidneys, oligohydramnios during late pregnancy, and persisting anuric renal failure. Despite intensive treatment, the patient suffered from severe hypotension and died at the age of 4 weeks. At autopsy, kidneys were found to be normal; on histology, deranged renal structures, in particular proximal tubuli and vessels, were noted, leading to the diagnosis of renal tubular dysgenesis (RTD). The diagnosis was confirmed by 2 heterozygous nonsense mutations of the ACE gene. Because the recurrence rate of RTD is 25% for the autosomal recessive trait, knowledge and genetic diagnosis of the disease is important for the parents.
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PMID:Oligohydramnios associated with sonographically normal kidneys. 2208 68

Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuria, pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1). Here, we review the series of 54 distinct mutations identified in 48 unrelated families. Most of them are novel and ACE mutations are the most frequent, observed in two-thirds of families (64.6%). The severity of the clinical course was similar whatever the mutated gene, which underlines the importance of a functional RAS in the maintenance of blood pressure and renal blood flow during the life of a human fetus. Renal hypoperfusion, whether genetic or secondary to a variety of diseases, precludes the normal development/ differentiation of proximal tubules. The identification of the disease on the basis of precise clinical and histological analyses and the characterization of the genetic defects allow genetic counseling and early prenatal diagnosis.
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PMID:Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis. 2209 42

The objective was to analyze the outcome following prenatal exposure to angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor antagonists (ARBs). For this purpose, a systematic review of published case reports and case series dealing with intrauterine exposure to ACE-Is or to ARBs using Medline as the source of data was performed. The publications retained for analysis included patients who were described individually, revealing, at minimum, the gestational age, substance used, period of medication intake, and the outcome. In total, 72 reports were included; 37 articles (118 well-documented cases) described the prenatal exposure to ACE-Is; and 35 articles (68 cases) described the prenatal exposure to ARBs. Overall, 52% of the newborns exposed to ACE-Is and 13% of the newborns exposed to ARBs did not exhibit any complications (P<0.0001). Neonatal complications were more frequent following exposure to ARBs and included renal failure, oligohydramnios, death, arterial hypotension, intrauterine growth retardation, respiratory distress syndrome, pulmonary hypoplasia, hypocalvaria, limb defects, persistent patent ductus arteriosus, or cerebral complications. The long-term outcome is described as positive in only 50% of the exposed children. Fetopathy caused by exposure to ACE-Is or ARBs has relevant neonatal and long-term complications. The outcome is poorer following exposure to ARBs. We propose the term "fetal renin-angiotensin system blockade syndrome" to describe the related clinical findings. Thirty years after the first description of ACE-I fetopathy, relevant complications are, at present, regularly described, indicating that the awareness of the deleterious effect of prenatal exposure to drugs inhibiting the renin-angiotensin system should be improved.
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PMID:Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review. 2275 20


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