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deletion ACE gene polymorphism is associated with reduced newborn kidney size
Abstracts
S99
Abstract UENPS.238 The insertion/deletion ACE gene polymorphism is associated with reduced newborn kidney size
Abstract UENPS.239 Angiotensin converting enzyme gene polymorphisms and acute renal failure in babies with RDS
Beata Loniewska⁎, Mariusz Kaczmarczyk, Anna Kuprjanowicz, Grazyna Adler, Agnieszka Binczak-Kuleta, Iwona Goracy, Agnieszka Kordek, Jacek Rudnicki, Andrzej Ciechanowicz PAM, Szczecin, Poland
Bilge Tanyeri, Canan Aygun⁎, Abdulkerim Bedir, Sukru Kucukoduk, Ozan Ozkaya Ondokuz Mayis University, Samsun, Turkey Background and aim
Background and aim Suboptimal nephron number may be associated with increased risk for essential hypertension and susceptibility to renal injury. All of the components of the renin–angiotensin system (RAS) are present in the developing kidney and play an important role in nephrogenesis. Several studies in animal models of fetal programming have shown that lower expression of RAS components during the active period of nephrogenesis is associated with lower nephron number and hypertension in later life. The ACE gene encoding angiotensin Iconverting enzyme, which has been mapped to human chromosome 17q23, has insertion/deletion (I/D) polymorphism in intron 16 consisting of a 287base pair Alu repeat sequence with three genotypes: II, ID, and DD. The DD homozygotes had higher plasma ACE levels than II subjects, and intermediate ACE levels were observed in ID heterozygotes. The genetic effect accounted for 47% of the total variance of serum ACE. Therefore, the aim of the study was to analyze an association between the I/D ACE polymorphism and subtle renal hypoplasia in healthy full-term newborn infants. Materials and methods The study group consisted of 93 healthy Polish infants who were born to women with uncomplicated pregnancies. Newborns delivered <36 weeks, or with low birth weight (<2500 g), genetic abnormalities, renal malformations or hydronephrosis as well as twins were excluded from the study. At birth, cord blood was obtained for isolation of leukocyte DNA. ACE genotypes were assessed by PCR. Left and right kidney volumes were measured by ultrasonography in newborns during the first 4 days of life with the following equation: [volume = 4/3 ??(length/2) (height/2) (width/2). Body surface area (BSA) was estimated from newborn length and weight with the following equation: BSA = (height × weight/3600) 1 / 2. Results Characteristics of the newborn cohort (n=93) are shown in Table 1. Twenty four II homozygotes, 43 ID heterozygotes and 26 DD homozygotes were found in the studied group. Mean (±SD) newborn length, right kidney volume, total kidney volume and total kidney volume/BSA were significantly higher in DD homozygotes as compared with II +ID subjects. The total kidney volume/BSA among newborns with at least one I allele (II +ID) was 10% lower than that in DD subjects. Conclusions Our results suggest that the reduced kidney size in normal newborns may be partially due to a common I/D ACE polymorphism.
The etiology of acute renal failure (ARF) in newborns is multifactorial. The incidence of ARF is reported as 6–24% in babies admitted to Neonatal Intensive Care Units (NICU); with a higher ratio in preterm babies. Especially small preterms with respiratory distress syndrome (RDS) are vulnerable to ARF. Hypotension, hypoxia, patent ductus arteriosus (PDA) are cited as etiological factors for ARF in babies with RDS, but genetical factors might also predispose some of these babies to ARF. The aim of this study is to determine the association between ARF and angiotensin converting enzyme (ACE) gene polymorphisms in preterm babies with RDS. Materials and methods One-hundred thirty two preterm babies followed in NICU between May 2005 and December 2007, diagnosed as RDS and receiving at least one dose of surfactant were included in the study. 2 ml of blood was obtained from these babies within the first hour of birth, during umbilical catheterization. ARF was diagnosed as serum creatinine >1.5 mg/dl (despite a normal maternal creatinine level) and/or oligo/anuria after the first 24 h of life. Babies were grouped as the ones with ARF and without ARF. The clinical characteristics, renal function tests, postnatal complications such as intraventricular hemorrhage (IVH), periventricular leucomalasia (PVL), retinopathy of prematurity (ROP), PDA and death were also recorded. Angiotensin converting enzyme gene genotypes from DNA samples were determined as DD, II and ID by polymerase chain reaction. The Hardy–Weinberg equilibrium was checked in all groups (all preterm babies, babies with ARF and babies without ARF) by x2 tests for each polymorphism. All the markers were in Hardy–Weinberg equilibrium. Results Thirty-nine (29.5%) of all preterm babies with RDS developed ARF. Vasomotor nephropathy was the leading cause of ARF in the study (79.5%). The second most common etiology for ARF was sepsis (20.5%). None of the babies had a congenital renal malformation leading to ARF. Genetic polymorphisms of ACE gene had no impact on the development of neonatal ARF in the study group. Besides, ACE gene polymorphisms did not affect the frequency of IVH, PVL, ROP and PDA. Sepsis and death were lower in babies with DD genotype. Conclusions ACE gene polymorphisms do not effect the development of ARF in premature babies with RDS. The study was supported by Ondokuz Mayis University Scientific Project Number: T-413. doi:10.1016/j.earlhumdev.2008.09.255
Table 1 Characteristics of study subjects with regard to ACE genotype Variable
Total
II + ID
DD
p
Gender (% female) Gestational age (week) Weight (g) BSA (m2) Left kidney volume (ml) Right kidney volume (ml) Total kidney volume (ml) Total kidney volume/BSA (ml/m2)
49.5 39.6 ± 1.3 3324.7 ± 555.6 0.227 ± 0.026 12.4 ± 3.5 11.9 ± 3.5 24.3 ± 6.7 106.9 ± 25.3
50.8 39.6 ± 1.2 3285.9 ± 557.1 0.224 ± 0.026 12.0 ± 3.0 11.3 ± 3.2 23.3 ± 5.9 103.6 ± 22.4
46.2 39.5 ± 1.4 3424.8 ± 549.9 0.232 ± 0.025 13.6 ± 4.4 13.4 ± 3.9 27.0 ± 8.2 115.4 ± 30.4
0.691 0.743 0.282 0.164 0.052 0.008 0.018 0.043
doi:10.1016/j.earlhumdev.2008.09.254
Abstract UENPS.240 The frequency of the urinary tract infection in term neonates with prolonged jaundice, Oromieh Iran Nader Pashapour⁎, Sarriyeh Golmohammadlou Oromieh Medical Science University, Oromieh, Iran Background and aim Breast-feeding is a major cause of prolonged jaundice and may disguise other important causes such urinary tract infection (UTI). The aim of this study was to evaluate the frequency of UTI and to determine the importance of performing UTI work-up in neonates with prolonged jaundice in an area with high breastfeeding rate.
S99
Abstract UENPS.238 The insertion/deletion ACE gene polymorphism is associated with reduced newborn kidney size
Abstract UENPS.239 Angiotensin converting enzyme gene polymorphisms and acute renal failure in babies with RDS
Beata Loniewska⁎, Mariusz Kaczmarczyk, Anna Kuprjanowicz, Grazyna Adler, Agnieszka Binczak-Kuleta, Iwona Goracy, Agnieszka Kordek, Jacek Rudnicki, Andrzej Ciechanowicz PAM, Szczecin, Poland
Bilge Tanyeri, Canan Aygun⁎, Abdulkerim Bedir, Sukru Kucukoduk, Ozan Ozkaya Ondokuz Mayis University, Samsun, Turkey Background and aim
Background and aim Suboptimal nephron number may be associated with increased risk for essential hypertension and susceptibility to renal injury. All of the components of the renin–angiotensin system (RAS) are present in the developing kidney and play an important role in nephrogenesis. Several studies in animal models of fetal programming have shown that lower expression of RAS components during the active period of nephrogenesis is associated with lower nephron number and hypertension in later life. The ACE gene encoding angiotensin Iconverting enzyme, which has been mapped to human chromosome 17q23, has insertion/deletion (I/D) polymorphism in intron 16 consisting of a 287base pair Alu repeat sequence with three genotypes: II, ID, and DD. The DD homozygotes had higher plasma ACE levels than II subjects, and intermediate ACE levels were observed in ID heterozygotes. The genetic effect accounted for 47% of the total variance of serum ACE. Therefore, the aim of the study was to analyze an association between the I/D ACE polymorphism and subtle renal hypoplasia in healthy full-term newborn infants. Materials and methods The study group consisted of 93 healthy Polish infants who were born to women with uncomplicated pregnancies. Newborns delivered <36 weeks, or with low birth weight (<2500 g), genetic abnormalities, renal malformations or hydronephrosis as well as twins were excluded from the study. At birth, cord blood was obtained for isolation of leukocyte DNA. ACE genotypes were assessed by PCR. Left and right kidney volumes were measured by ultrasonography in newborns during the first 4 days of life with the following equation: [volume = 4/3 ??(length/2) (height/2) (width/2). Body surface area (BSA) was estimated from newborn length and weight with the following equation: BSA = (height × weight/3600) 1 / 2. Results Characteristics of the newborn cohort (n=93) are shown in Table 1. Twenty four II homozygotes, 43 ID heterozygotes and 26 DD homozygotes were found in the studied group. Mean (±SD) newborn length, right kidney volume, total kidney volume and total kidney volume/BSA were significantly higher in DD homozygotes as compared with II +ID subjects. The total kidney volume/BSA among newborns with at least one I allele (II +ID) was 10% lower than that in DD subjects. Conclusions Our results suggest that the reduced kidney size in normal newborns may be partially due to a common I/D ACE polymorphism.
The etiology of acute renal failure (ARF) in newborns is multifactorial. The incidence of ARF is reported as 6–24% in babies admitted to Neonatal Intensive Care Units (NICU); with a higher ratio in preterm babies. Especially small preterms with respiratory distress syndrome (RDS) are vulnerable to ARF. Hypotension, hypoxia, patent ductus arteriosus (PDA) are cited as etiological factors for ARF in babies with RDS, but genetical factors might also predispose some of these babies to ARF. The aim of this study is to determine the association between ARF and angiotensin converting enzyme (ACE) gene polymorphisms in preterm babies with RDS. Materials and methods One-hundred thirty two preterm babies followed in NICU between May 2005 and December 2007, diagnosed as RDS and receiving at least one dose of surfactant were included in the study. 2 ml of blood was obtained from these babies within the first hour of birth, during umbilical catheterization. ARF was diagnosed as serum creatinine >1.5 mg/dl (despite a normal maternal creatinine level) and/or oligo/anuria after the first 24 h of life. Babies were grouped as the ones with ARF and without ARF. The clinical characteristics, renal function tests, postnatal complications such as intraventricular hemorrhage (IVH), periventricular leucomalasia (PVL), retinopathy of prematurity (ROP), PDA and death were also recorded. Angiotensin converting enzyme gene genotypes from DNA samples were determined as DD, II and ID by polymerase chain reaction. The Hardy–Weinberg equilibrium was checked in all groups (all preterm babies, babies with ARF and babies without ARF) by x2 tests for each polymorphism. All the markers were in Hardy–Weinberg equilibrium. Results Thirty-nine (29.5%) of all preterm babies with RDS developed ARF. Vasomotor nephropathy was the leading cause of ARF in the study (79.5%). The second most common etiology for ARF was sepsis (20.5%). None of the babies had a congenital renal malformation leading to ARF. Genetic polymorphisms of ACE gene had no impact on the development of neonatal ARF in the study group. Besides, ACE gene polymorphisms did not affect the frequency of IVH, PVL, ROP and PDA. Sepsis and death were lower in babies with DD genotype. Conclusions ACE gene polymorphisms do not effect the development of ARF in premature babies with RDS. The study was supported by Ondokuz Mayis University Scientific Project Number: T-413. doi:10.1016/j.earlhumdev.2008.09.255
Table 1 Characteristics of study subjects with regard to ACE genotype Variable
Total
II + ID
DD
p
Gender (% female) Gestational age (week) Weight (g) BSA (m2) Left kidney volume (ml) Right kidney volume (ml) Total kidney volume (ml) Total kidney volume/BSA (ml/m2)
49.5 39.6 ± 1.3 3324.7 ± 555.6 0.227 ± 0.026 12.4 ± 3.5 11.9 ± 3.5 24.3 ± 6.7 106.9 ± 25.3
50.8 39.6 ± 1.2 3285.9 ± 557.1 0.224 ± 0.026 12.0 ± 3.0 11.3 ± 3.2 23.3 ± 5.9 103.6 ± 22.4
46.2 39.5 ± 1.4 3424.8 ± 549.9 0.232 ± 0.025 13.6 ± 4.4 13.4 ± 3.9 27.0 ± 8.2 115.4 ± 30.4
0.691 0.743 0.282 0.164 0.052 0.008 0.018 0.043
doi:10.1016/j.earlhumdev.2008.09.254
Abstract UENPS.240 The frequency of the urinary tract infection in term neonates with prolonged jaundice, Oromieh Iran Nader Pashapour⁎, Sarriyeh Golmohammadlou Oromieh Medical Science University, Oromieh, Iran Background and aim Breast-feeding is a major cause of prolonged jaundice and may disguise other important causes such urinary tract infection (UTI). The aim of this study was to evaluate the frequency of UTI and to determine the importance of performing UTI work-up in neonates with prolonged jaundice in an area with high breastfeeding rate.