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)

Renal scarring with and without vesicoureteral reflux (VUR) has been now recognized as an important cause of paediatric hypertension for many years [1-5]. However, its pathogenesis has still remained uncleared. The widespread concept implicated the activation of renin-angiotensin system finding a powerfull support in higher peripheral plasma renin activity (PRA) in children with reflux nephropathy than in controls [6, 7] and in beneficial antihypertensive effects of ACE inhibitors. The latter, in form of captopril, has also been used in captopril test and in renal scintigraphy and isotope renography following the administration of captopril to provide evidence for renin dependent hypertension [8, 9]. Published studies of captopril test have centred on the identification of renovascular as opposed to essential hypertension [10-18, 20-22]. The aim of our study was to assess the usefulness of captopril test in differentiation between hypertensive children with renal scarring from those with essential hypertension. We studied blood pressure (BP) and PRA responses to a single dose of captopril in two groups of hypertensive children. Group A consisted of 29 patients, 14 boys and 15 girls, who had renal scaring as demonstrated by renal 99mTc dimercaptosuccinid acid scan (99m Tc DMSA) and/or intravenous pyelography. Group B included 19 patients, 19 boys and 10 girls who had arterial hypertension, while clinical examination excluded renal and other definable causes of BP elevation, and they were therefore considered to have essential hypertension. At the time of the study all patients had normal glomerular filtration rate and were not salt depleted. They did not receive any antihypertensive medication for at least two weeks. The test was performed in the morning in fasting sitting patients. At the start of the test a small vein in the hand or forearm was cannulated to permit blood sampling. BP was measured 10, 20, and 30 minutes before captopril administration to get baseline BP (mean of these three measurements) and to allow the children to become accustomed to the test procedure. A single oral dose of captopril 0.64 +/- 0.04 mg/kg body weight was given to patients from group A and almost the same dose of captopril, 0.63 +/- 0.05 mg/kg body weight, to patients from group B. The patients remained sitting and BP was measured every 15 minutes during an hour. Blood for PRA was drown in the sitting position (17 patients from group A and 16 patients from group B) before and one hour after the dose of captopril. Samples of blood for basal PRA were collected from 16 patients from group A and in 14 patients from in B in lying position after waking up in the morning. PRA was measured by radioimmunoassay using a commercially available kit, SB-REN 2, from CIS Bio International. According to the criteria of Muller et al. [10] the captopril test was positive if the post-captopril PRA (ng/ml/h) was greater than or equal to 12 with an increase of greater than or equal to 10 and relative increase of greater than or equal to 15% (400% if initial PRA was < 3). The results of our study are presented in Tables 1 and 2 and in Graphs 1 and 2. The age of patients, doses of captopril, initial BP and PRA before the use of captopril did not much differ between studied groups. Fall of BP and PRA increase were highly significant (p < 0.001) both in group A and group B. However, the hypotensive reaction of diastolic BP and MAP were more pronounced in group A (14.45 +/- 1.67% and 15.81 +/- 1.62%) than in group B (6.95 +/- 2.21% and 8.96 +/- 1.75%; p < 0.01), but there were no significant differences in PRA and systolic BP changes and positive results of captopril test between the studied groups. Hypotensive responses of diastolic BP and MAP greater than 10% of initial values were found to be more frequent in group A (79.32% and 79.31%) than in group B (26.61% and 31.57 degrees %; p < 0.001 and p < 0.01). Diastolic BP and MAP were directly related to the dose of cap
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PMID:[The captopril test--an aid in the detection of scarring nephropathy as a cause of arterial hypertension in children]. 1064 99

The objective of this study was to investigate whether mutations of the renin-angiotensin system genes are involved in primary vesicoureteric reflux (VUR) and VUR-associated renal scarring. The M235T polymorphism of the angiotensinogen ( ATG) gene, the I/D polymorphism of the angiotensin converting enzyme ( ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor ( AT1) gene were identified in 77 patients with primary VUR (aged 6.9+/-3.2 years, mean+/-SD) and 80 healthy controls (aged 33+/-7 years). Thirty-eight of the 77 VUR patients had low-grade VUR (grade I-III) and 39 had high-grade VUR (grade IV and V). Renal scarring was found in 43 VUR patients, while 34 patients had normal kidneys on dimercaptosuccinic acid scan. The ACE gene polymorphism was determined by polymerase chain reaction and the ATG and AT1 gene polymorphisms were determined by single-step LightCycler technology. We found significant over-representation of the DD genotype in patients with renal scarring (44 %) compared with normal controls (23%, P<0.05) and patients with no scar formation (21%, P<0.05). Significantly higher D and significantly lower I allele frequencies were present in VUR patients with scarred kidneys (D allele 0.64 and I allele 0.36) compared with controls (D allele 0.53 and I allele 0.47, P<0.05) and patients with unscarred kidneys (D allele 0.4 and I allele 0.6, P<0.05). No differences in the ATG and AT1 genotype distributions and allele frequencies were observed in VUR patients compared with the normal population. The DD genotype and D allele of ACE may be a genetic susceptibility factor contributing to scar formation in VUR. We detected no linkage of genetic polymorphisms of ATG and AT1 to VUR and VUR-associated renal scarring.
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PMID:ACE gene polymorphism and renal scarring in primary vesicoureteric reflux. 1247 52

The objective of this study was to investigate whether DNA polymorphisms of the renin-angiotensin system (RAS) genes were associated with renal scar formation in pediatric patients with bladder dysfunction (BD). Although these children are born healthy, due to persistence of immature voiding habits and evolution of BD, some develop progressive renal damage. It has been suggested that the DD genotype of the angiotensin I-converting enzyme (ACE) gene might be an adverse renal prognostic factor. The insertion/deletion (I/D) polymorphism of the ACE gene and the A1166C polymorphism of the angiotensin II type 1 receptor (ATR1) gene were identified by polymerase chain reaction amplification in 42 children with BD (aged 5-14 years) and 198 healthy adult controls. Twelve children had urgency syndrome and 30 had dysfunctional voiding. Renal scarring was found in 16 patients, while 26 patients had normal kidneys on dimercaptosuccinic acid scan. In children with renal lesions there was significant over-representation of the DD genotype compared with either controls or patients without renal damage ( P<0.05). On multivariate analysis, the DD genotype was the only factor that had a significant impact on renal scar formation, introducing a 2.51-fold risk (odds ratio 2.51, 95% confidence interval 1.04-6.04, P=0.04). The A1166C gene polymorphism was not significantly associated with the development of parenchymal damage in children with BD. Our findings introduce ACE I/D gene polymorphism as an independent risk factor for parenchymal destruction in pediatric patients with BD.
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PMID:ACE and AT1 receptor gene polymorphisms and renal scarring in urinary bladder dysfunction. 1517 69