Angiotensin‐converting enzyme gene insertion/deletion polymorphism and renal damage in childhood uropathies

Al‐Eisa, Amal; Haider, M.Z.; Srivastva, B S

doi:10.1046/j.1442-200x.2000.01242.x

Cited by 11 publications

(14 citation statements)

References 26 publications

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“…However, available reports gave conflicting results. In a study from Kuwait, an association has been found between this type of polymorphism in Kuwaiti Arab children with congenital urologic abnormalities including VUR and the occurrence of parenchymal renal damage [18].…”

Section: Discussionmentioning

confidence: 97%

Acute pyelonephritis and renal scarring in Kuwaiti children: a follow-up study using 99mTc DMSA renal scintigraphy

et al. 2005

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The aim of this study was to determine the prevalence of renal scarring in a group of Kuwaiti Arab children with their first documented acute pyelonephritis (APN). Eighty-two Kuwaiti Arab children (10 males and 72 females) who had abnormal (99m)Tc DMSA renal scan findings of acute pyelonephritis were prospectively studied with the same imaging modality 6 months after treatment to identify those who developed renal scarring. A micturition cystourethrogram (MCUG) was performed for all of the children 1 month after diagnosis. Children were divided into 3 age groups (<2 years, 2-5 years and above 5 years). The follow-up DMSA renal scans 6 months after diagnosis revealed normalization of renal changes in 56% (46 patients), much improvement with residual renal abnormality in 6% (5 patients), and persistent parenchymal defects in 38% (31 patients). Vesicoureteric reflux (VUR) was found in 32% of children (26/82) and the majority were between grade I and III. Thirteen of those with VUR (50%) developed renal scars on follow-up. Fifty-three percent of the scarred kidneys (19/36) were drained by non-refluxing ureters. In this study, children older than 2 years had less VUR yet were more susceptible to APN and to the development of renal scars. Girls were more prone to developing APN and renal scarring than boys. This work shows that APN is a serious cause for renal scarring in our patients, particularly if associated with other risk factors such as recurrent infections and the female sex.

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Section: Discussionmentioning

confidence: 97%

Acute pyelonephritis and renal scarring in Kuwaiti children: a follow-up study using 99mTc DMSA renal scintigraphy

et al. 2005

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“…An ACE gene insertion-deletion (I/D) polymorphism has been shown to influence the circulating and cellular ACE concentration [14][15][16]. Its D allele is associated with a higher risk of developing a number of vascular disorders [17][18][19][20]. We have investigated the prevalence of ACE gene I/D polymorphism genotypes in premature Kuwaiti newborns to investigate their association with ROP and progression to advanced stages.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism in Kuwaiti Children with Retinopathy of Prematurity

et al. 2002

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Retinopathy of prematurity (ROP) is a disease characterized by neovascularization which occurs in infants with short gestational age and low birth weight and can lead to retinal detachment and blindness. In a proportion of ROP cases, the disease progresses to advanced stages despite rigorous intervention. The genotypes for angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism were determined in 181 premature Kuwaiti infants using a polymerase chain reaction (PCR) method. The incidence of different I/D genotypes was compared in ROP cases (n = 74) and non-ROP controls (n = 107) and within 2 subgroups of ROP patients: (1) in which ROP regressed spontaneously (stages 1–3, n = 53), and (2) in which ROP progressed to advanced stages (stages 4 and 5, n = 21). When the ROP cases were considered collectively as one group, the incidence of the DD genotype was almost identical to that of non-ROP controls. The incidence of heterozygous ID genotype was higher in non-ROP controls. The incidence of the II genotype was higher in ROP cases compared to non-ROP controls (p < 0.01). In contrast to this, when ROP cases were divided in 2 subgroups the incidence of the DD genotype was significantly higher in advanced stage ROP cases compared to spontaneously regressing ROP cases (p < 0.04). The incidences of ID and II genotypes were not significantly different amongst the 2 subgroups of ROP patients.

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“…Angiotensin I-converting enzyme (ACE) is one of the most intensely studied candidate genes in human renal malformations (11)(12)(13). The insertion or deletion (I/D) of a 287-bp fragment in intron 16 of the ACE gene has proved to influence the activity of the renin-angiotensin system (14) and, therefore, the production of angiotensin II.…”

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confidence: 99%

Angiotensin-Converting Enzyme and Angiotensin Type 2 Receptor Gene Genotype Distributions in Italian Children with Congenital Uropathies

et al. 2004

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Angiotensin I-converting enzyme (ACE) and angiotensin type 2 receptor (AT2R) gene polymorphisms have been associated with an increased incidence of congenital anomalies of the kidney and urinary tract (CAKUT). We investigated the genotype distribution of these polymorphisms in Italian children with CAKUT. We also evaluated the association between the ACE insertion/deletion and the AT2R gene polymorphisms with the progression of renal damage in subgroups of CAKUT patients. We recruited 102 Italian children with CAKUT; 27 with vesicoureteral reflux; 12 with hypoplastic kidneys; 20 with multicystic dysplastic kidneys; 13 with ureteropelvic junctions stenosis/ atresia; 18 with nonobstructed, nonrefluxing primary megaureters; and 12 with posterior urethral valves and compared them with 92 healthy control subjects. ACE and AT2R gene polymorphisms were analyzed by PCR. The identification of AT2R gene polymorphisms in intron 1 and in exon 3 was revealed by enzymatic digestion. ACE genotype distribution in children with CAKUT was no different from that of the control subjects, but the subgroup of patients with radiographic renal parenchymal abnormalities showed an increased occurrence of the D/D genotype. The frequency of the G allele of AT2R gene in children with CAKUT was increased in respect to that of the control subjects. By contrast, no significant difference in the frequency of the C and A alleles of the AT2R gene was found. Our findings indicate that the ACE gene can be a risk factor in the progression of renal parenchymal damage in CAKUT patients. Moreover, a major role of the AT2R gene in the development of CAKUT has been found, at least in Italian children. Congenital anomalies of the kidney and urinary tract (CAKUT) are now considered a major cause of renal failure in children (1). Ureteropelvic junction (UPJ) stenosis/atresia is the most common cause of a palpable abdominal mass in the newborn. Other forms of CAKUT include vesicoureteral reflux (VUR); hypoplastic kidney (HK); multicystic dysplastic kidney (MCDK); nonobstructed, nonrefluxing primary megaureter (MU); and bladder outlet obstruction [e.g. posterior urethral valves (PUV)] (2). A number of well-recognized but puzzling features are associated with CAKUT. Anomalies such as UPJ stenosis/atresia and MCDK are often unilateral or highly asymmetrical.Some of these anomalies are often concurrent (3-5). It is also noteworthy to mention that these abnormalities often take a familial pattern, showing incomplete and variable genetic penetrance. For this reason, it is believed that these assorted anatomic anomalies may share a common genetic cause (6 -8).

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Angiotensin‐converting enzyme gene insertion/deletion polymorphism and renal damage in childhood uropathies

Abstract: Our data suggest an association of D allele of the ACE gene insertion/deletion polymorphism and congenital urological abnormalities, which result in parenchymal damage in Kuwaiti Arab children.

Cited by 11 publications

References 26 publications

Acute pyelonephritis and renal scarring in Kuwaiti children: a follow-up study using 99mTc DMSA renal scintigraphy

Acute pyelonephritis and renal scarring in Kuwaiti children: a follow-up study using 99mTc DMSA renal scintigraphy

Angiotensin-Converting Enzyme Gene Insertion/Deletion Polymorphism in Kuwaiti Children with Retinopathy of Prematurity

Angiotensin-Converting Enzyme and Angiotensin Type 2 Receptor Gene Genotype Distributions in Italian Children with Congenital Uropathies

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