Congenital Urological Abnormalities Research Articles

MP53-14 RENAL FUNCTION BY EGFR CALCULATORS IN PRUNE BELLY SYNDROME AND POSTERIOR URETHRAL VALVES

You have accessJournal of UrologyCME1 Apr 2023MP53-14 RENAL FUNCTION BY EGFR CALCULATORS IN PRUNE BELLY SYNDROME AND POSTERIOR URETHRAL VALVES Alexandra Carolan, Shane Batie, Samuel Gold, Shaheer Ali, Daniel Wong, Nida Karra, Nathalia Amado, Jyothsna Gattineni, Bruce Schlomer, Yvonne Chan, and Linda Baker Alexandra CarolanAlexandra Carolan More articles by this author , Shane BatieShane Batie More articles by this author , Samuel GoldSamuel Gold More articles by this author , Shaheer AliShaheer Ali More articles by this author , Daniel WongDaniel Wong More articles by this author , Nida KarraNida Karra More articles by this author , Nathalia AmadoNathalia Amado More articles by this author , Jyothsna GattineniJyothsna Gattineni More articles by this author , Bruce SchlomerBruce Schlomer More articles by this author , Yvonne ChanYvonne Chan More articles by this author , and Linda BakerLinda Baker More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003301.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In prune belly syndrome (PBS), prior comparison of estimated glomerular filtration rate (eGFR) with calculators using creatinine (Cr) and/or Cystatin C (Cys) showed lower mean eGFR with Cys-based calculators than with the “Bedside Schwartz” Cr-based calculator (eGFRcr) in Chronic Kidney Disease (CKD) 1 and 2. As abdominal skeletal muscle paucity in PBS could reduce serum Cr, we hypothesized the differences in mean eGFRcr and eGFR by Cys-based calculators (denoted as Δ) will be greater in PBS compared to posterior urethral valves (PUV), with intact musculature. METHODS: A 2014-2021 retrospective ICD-10 search identified PBS and PUV patients with labs and height without neuromuscular disorders or renal replacement. eGFRcr, eGFRcys and creatinine-cystatin C-based GFR (eGFR-CKiD) were calculated. CKD stages were assigned by eGFRcr. Δ eGFRcr, eGFRcys, and eGFR-CKiD between PBS and PUV were compared with t-test. Those with normal Cr and/or Cys but who had CKD by eGFR calculators were identified. The proportion of changes in CKD staging by each calculator was compared with chi-square or Fishers exact test. RESULTS: 95 PUV and 26 PBS patients were analyzed (Figure 1). Δ eGFRCr and eGFR with Cys-based calculators by CKD stage or by all CKD stages combined were not different between PBS and PUV. By all CKD stages combined, Δ eGFRcr and eGFRcys was 18 and 13 mL/min/1.73 m2 in PBS and PUV, respectively (p=0.22) and Δ eGFRcr and eGFR-CKiD was 8 and 5 ml/min/1.73 m2 in PBS and PUV, respectively (p=0.71). Among patients with normal Cr and/or Cys, at least 25% had CKD2-3 by eGFR calculation. Changes in CKD stage by Cys-based calculators compared to eGFRcr were not significantly different between PBS and PUV (p>0.3). Upstaging was most frequent in PBS and PUV CKD1 and 2. CONCLUSIONS: Differences between eGFRcr and eGFR by Cys-based calculators in PBS and PUV patients were not significant, suggesting paucity of abdominal musculature in PBS may not account for the lower eGFRs observed using Cys-based calculators. In 25% of patients, normal Cr and/or Cys actually had CKD2-3, highlighting importance of eGFR calculation. Cys-based calculators upstaged, especially in CKD1 and 2. Cys-based eGFRs calculators should be considered for early identification of CKD in patients with congenital urologic abnormalities prone to renal dysfunction. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e717 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexandra Carolan More articles by this author Shane Batie More articles by this author Samuel Gold More articles by this author Shaheer Ali More articles by this author Daniel Wong More articles by this author Nida Karra More articles by this author Nathalia Amado More articles by this author Jyothsna Gattineni More articles by this author Bruce Schlomer More articles by this author Yvonne Chan More articles by this author Linda Baker More articles by this author Expand All Advertisement PDF downloadLoading ...

Trends and risk factors of extended-spectrum beta-lactamase urinary tract infection in Chinese children: a nomogram is built and urologist should act in time.

BackgroundTo investigate the etiological characteristics and risk factors of extended-spectrum beta-lactamase (ESBL) urinary tract infection (UTI) and construct a corresponding nomogram to predict the probability of ESBL(+) UTI.MethodsWe retrospectively reviewed the records among patients experiencing UTI events in Chongqing Medical University Affiliated Children’s Hospital from 1994 and 2019.ResultsA total of 854 patients with UTI were evaluated and ESBL-producing bacteria increased significantly. Significant potential risk factors of ESBL-UTI were congenital urological abnormalities, vesicoureteral reflux, neurologic disorder, age <12 months, fever and previous use of antibiotics. On logistic regression analysis, neurological disorder (OR =8, 95% CI: 1.845–34.695) and antibiotics administration in the last 3 months (OR =4.764, 95% CI: 3.114–7.289) were identified as an independent significant risk factor for ESBL-UTI. The nomogram generated was well calibrated for all predictions of ESBL+ probability, and the accuracy of the model nomogram measured by Harrell’s C statistic (C-index) was 0.741.ConclusionsThe current situation of multiple bacterial antibiotic resistance has become a worrisome issue in UTI and early identification of ESBL production is important in terms of appropriate treatment and effective infection control. We may choose broad-spectrum antibiotics as empirical antibiotics for UTI among children with neurological disease and used antibiotic in the last three months.

Long-term urology outcomes of anorectal malformation

Urological problems are a recognised feature of anorectal malformation (ARM). Previous assumptions of favourable long-term urinary outcomes are being challenged. We hypothesised that urinary tract problems are common in ARM and frequently persist into adulthood. We retrospectively reviewed long-term renal and bladder outcomes in ARM patients. Patients with ARM born between 1984-2005 were identified from electronic hospital databases. Their case notes were reviewed. Renal outcomes included serum creatinine and the need for renal replacement therapy. Bladder outcomes included symptom review, bladder medication, need for intermittent catheterisation, videourodynamics and whether the patient had undergone augmentation cystoplasty. RESULT (TABLE 1): The case notes of 50 patients were reviewed. The median age at last follow up was 18 years (range 12-34 years). The level of fistula was noted to be high in 17 patients, intermediate in eight, and low in 10. Four had cloaca. Congenital urological abnormalities were present in 25 (50%). An abnormal spinal cord was present in 22 (44%) patients. VACTERL association occurred in 27 (54%). Chronic kidney disease stage II or above was found in 14 (28%) patients, of whom four required a renal transplant. Abnormal bladder outcomes were found in 39 (78%) patients. Augmentation cystoplasty with Mitrofanoff had been performed in 12. Of those who had not undergone cystoplasty, 17 had urinary symptoms, including urinary incontinence in 12. Of the 39 patients with abnormal bladder outcome, 19 (49%) did not have a spinal cord abnormality. There was no significant statistical association between level of ARM and abnormal renal outcome or presence of bladder abnormality. Adverse renal and bladder outcomes are common in our cohort of young people with ARM with a significantly higher incidence compared with current literature. We did not demonstrate an association between level of ARM or presence of spinal cord anomaly with persistent bladder problems. Congenital urological anomalies are more common in those who later have an abnormal renal outcome. Although this difference is statistically significant, one fifth of patients born with anatomically normal upper tracts develop reduced renal function, implying an important acquired component. Bladder problems and reduced renal function affect a significant proportion of young adults with ARM. Neither adverse outcome is reliably predicted from ARM level, congenital urological anomaly or spinal cord anomaly. We advise continued long-term bladder and kidney follow-up for all patients with ARM.

The effect of orcidopexy on increasing testicular volume in undescended testis

Undescended Testis (UDT), a common congenital urological abnormality, which is one of the causes of male infertility. Testicular volume in UDT is significantly smaller than normal testicles. After orchidopexy procedure, testicular volume is expected to increase significantly. The subjects of the study were patients with a diagnosis of UDT palpable which was divided into 2 groups of 0-2 years and over 2 years. Assessment of testicular volume using ultrasound performed before and after surgery. The average age of patients is 6.56±4.248years with the age group 0-2 years are 6 or 20% and> 2 years are 35 or 80%. In the 0-2 years age group, the percentage change in left testicular volume has an average of 14.07 ± 10.590%. In the age group> 2 years, the percentage change in volume of the left testis has an average of 3.19 ± 2.626% with p value = 0.009. In the age group 0-2 years, the percentage change in right testicular volume has an average of 13.25 ± 4.792%. In the age group> 2 years, the percentage change in the volume of the right testis has an average of 5.91 ± 7.012% with p value = 0.042. There is a significant correlation between testicular volume before and after orchidopexy surgery. And changes in testicular volume in the 0-2years age group were more significant than changes in testicular volume in the age group> 2 years

Interstitial Cells of Cajal and their Correlation to Outcome in Congenital Urological Abnormalities.

Interstitial Cells of Cajal and their Correlation to Outcome in Congenital Urological Abnormalities.

Case 1: Term Infant with Intractable Seizures and Bilateral Hydronephrosis

A male neonate is born via vaginal delivery at 37 1/7 weeks’ gestation to a healthy 30-year-old gravida 3, para 2 mother. The pregnancy had been complicated by polyhydramnios, severe fetal hydronephrosis, anti-Kell antibodies, and questionable fetal mega cisterna magna. Labor is induced secondary to worsening bilateral fetal hydronephrosis. The delivery is uncomplicated and Apgar scores are 9 and 9 at 1 and 5 minutes, respectively. Initial physical examination findings are significant only for left-sided club foot, and the infant is admitted to the well-newborn nursery. State newborn screening is performed 24 hours after birth, results of which are normal. There is no significant familial history of congenital neurologic or urologic abnormalities, and both previous children of these parents are healthy. Amniocentesis performed during this pregnancy secondary to the bilateral fetal hydronephrosis had revealed a normal fetal microarray. The infant is admitted to the NICU 3 days after birth secondary to hypernatremia (150 mEq/L [150 mmol/L]) and severe (grade 4) bilateral hydronephrosis confirmed with postnatal ultrasonography. While in the NICU, the neonate is noted to have episodes of lateral eye deviation, bilateral arm and leg twitching, and episodes of apnea. Electrolytes (excluding hypernatremia), glucose, and cranial ultrasonography findings are normal. A sepsis evaluation is completed and the infant is treated for 48 hours with ampicillin, cefotaxime, and acyclovir until blood, urine, and cerebrospinal fluid cultures return negative. Amplitude-integrated electroencephalography (EEG) findings are concerning for seizure activity and video EEG shows frequent multifocal epileptiform activity in both hemispheres indicative of abnormal cortical hyperexcitability, lowering the threshold for seizures. Following consultation with pediatric neurology he receives a loading dose of levetiracetam and maintenance therapy is initiated. Brain magnetic resonance imaging (MRI) reveals trace right occipital subarachnoid hemorrhage and trace infratentorial posterior fossa subdural hematoma thought to be secondary to birth trauma and …

A Case of Focal Segmental Glomerulosclerosis in Turner Syndrome

Turner syndrome is usually accompanied with various anomalies. Congenital urological and renal abnormalities are often associated with this syndrome. The occurrence of glomerulonephritis is uncommon. An 18-year-old woman showed fatigue and profound proteinuria. She had been diagnosed with Turner syndrome in her age of 15. The kidney biopsy specimen examined by light microscopy, immunofluorescence and electron microscopic examination revealed focal segmental glomerulosclerosis. This is the first case report of focal segmental glomerulosclerosis in turner syndrome in South Korea.

660 EPIDIDYMOORCHITIS IN PEDIATRIC PATIENTS: ARE ANTIBIOTICS NECESSARY?

You have accessJournal of UrologyPediatrics: Urinary Tract Infection/Vesicoureteral Reflux1 Apr 2013660 EPIDIDYMOORCHITIS IN PEDIATRIC PATIENTS: ARE ANTIBIOTICS NECESSARY? Evalynn Vasquez, Brendan Frainey, Michaella Prasad, Bruce Lindgren, and Earl Cheng Evalynn VasquezEvalynn Vasquez Chicago, IL More articles by this author , Brendan FraineyBrendan Frainey Chicago, IL More articles by this author , Michaella PrasadMichaella Prasad Chicago, IL More articles by this author , Bruce LindgrenBruce Lindgren Chicago, IL More articles by this author , and Earl ChengEarl Cheng Chicago, IL More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.213AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Traditionally, pediatric patients with epididymoorchitis (EO) are treated with antibiotic therapy despite negative results found on urinalysis and urine culture. The purpose of this study is to identify the relationship between urinalysis and urine culture results with treatment of these patients. METHODS A query was performed for males aged 0-12 years who presented to the Emergency Department from 2000-2010 in which an ICD9 code had been entered for EO, scrotal pain, torsion of testis or appendix epididymis/testis, or unspecified disorder of male genitalia in order to capture all patients with a final diagnosis of EO. Patients with hypervascularity of the epididymis/testis demonstrated on a scrotal ultrasound were included. Exclusion criterion was known congenital urologic abnormalities. Through a retrospective chart review, data was collected regarding patient history, physical examination, laboratory and radiology results, treatment, and follow up. Data was analyzed to determine the correlation between presentation, urinalysis/urine culture, and treatment. RESULTS 2412 patients were identified using the described ICD9 code query. 161 patients met inclusion criteria. Median age was 9.1 years (range 0.2-12 years). Urine was collected in 144 patients. 135 (94%) had a negative urinalysis and 9 (6%) had a positive urinalysis. Only 3 patients had both positive urinalysis and urine culture. All 3 patients were 6 months old or less, not circumcised, and had urine specimens obtained by catheterization. The remaining 6 patients with a positive urinalysis had negative urine cultures. A total of 74 (46%) patients were treated with antibiotics. 87 (54%) patients were treated with nonsteroidal anti-inflammatories, acetaminophen, and supportive measures. Urinalysis/culture results did not correlate with antibiotic treatment (p=0.23). Follow up was available on 59 patients. Median follow up was 3 weeks. 39 patients reported resolution of symptoms, 14 reported persistent symptoms, 5 reported worsening symptoms. There was no statistically significant difference between resolution, persistence, or worsening of symptoms and antibiotic treatment (p=0.92). CONCLUSIONS Our study found that sterile urine is exclusively found in boys greater than 1 year of age diagnosed with EO. This suggests, that in this population, EO is noninfectious in nature and implies an inflammatory response from sterile urine (chemical EO) that does not require antibiotic treatment. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e270 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Evalynn Vasquez Chicago, IL More articles by this author Brendan Frainey Chicago, IL More articles by this author Michaella Prasad Chicago, IL More articles by this author Bruce Lindgren Chicago, IL More articles by this author Earl Cheng Chicago, IL More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Robot-Assisted Management of Congenital Renal Abnormalities in Adult Patients

Congenital anomalies of the genitourinary tract are usually diagnosed and corrected in childhood. Robot-assisted management of congenital urologic abnormalities in adult patients has not been described previously. We present a series of patients with congenital renal abnormalities diagnosed in adulthood and managed using a robotic approach. Four patients at our institution were identified with congenital renal abnormalities diagnosed in adulthood. One had a duplicated collecting system with hydronephrosis of a thinned out upper pole moiety and underwent heminephroureterectomy. A second had right hydronephrosis, complete atrophy of the right renal cortex, and a dilated tortuous ureter with obstructing ureterocele and underwent simple nephrectomy. A third patient had a duplicated system with distal ureteral reflux and an ureterocele and underwent ureteroureterostomy and distal ureterectomy. The fourth had a duplicated collecting system with ureterovaginal fistula of the upper pole moiety. Perioperative variables were collected including operative time, estimated blood loss, length of hospital stay, and change in estimated creatinine clearance. Mean age was 35 years (range 16-54), mean body mass index was 30.9 kg/m(2) (21.8-42.5), and mean baseline estimated creatinine clearance was 147.7 mL/minutes (107.7-214.6). Mean operative time was 258 minutes (151-374) and mean estimated blood loss was 44 mL (25-50). Postoperative estimated creatinine clearance was 133.1 mL/minutes (115.9-160.9), which was not statistically different from preoperative values (p = 0.608). All patients were discharged by postoperative day 2. There were no perioperative complications. Robot-assisted management of congenital renal abnormalities is a feasible and efficacious treatment modality in adult patients with low morbidity and good outcomes.

Pelvo-ureteric junction obstruction in the lower pole moiety of a duplex kidney with an associated intraparenchymal abscess: a case report

IntroductionPelvo-ureteric junction obstruction and duplex kidney are common radiological findings. However, pelvo-ureteric junction obstruction in a duplex kidney is a rare finding. We present the case of a patient who presented with septic complications secondary to this combination.Case presentationAn adult woman presented with urinary sepsis, and her initial investigation with ultrasound revealed hydronephrosis of the lower moiety of a duplex kidney. Further investigations with computed tomography and magnetic resonance imaging showed an associated intrarenal abscess and a pelvo-ureteric junction obstruction of the lower moiety of a duplex kidney.ConclusionThis patient had a rare and unreported complication of an unusual congenital urological abnormality. This case report highlights the role of multiple imaging modalities in correct diagnosis for clinical management.

Congenital genitourinary anomalies and sexual function

Congenital urologic abnormalities in males may contribute to sexual dysfunction seen in young men. It is the purpose of this paper to review some of the more common congenital urologic anomalies and their impact on sexual and reproductive function.

Inflamation of the testis and epidididymis in an otherwise healthy child: Is it a true bacterial urinary tract infection?

Purpose The exact etiology of acute gonadal inflamation (EO) in children is unknown. Bacterial infection and underlying urological abnormalities are thought to be the main causes, and hence antibiotic treatment and further invasive urinary tract imaging studies are usually recommended. The purpose of this study was to assess the role of bacterial infection in pediatric acute EO. Materials and methods We retrospectively searched our electronic medical archive for children under the age of 18 years with the diagnosis of acute EO between 1997 and 2002. Patients' charts were retrieved and reviewed for clinical and laboratory data. Results During 1997–2002, 193 patients with acute EO were treated. There were two subgroups according to the results of urinary cultures: 182 children (94.3%) had negative urine cultures and 11 (5.7%) had positive cultures. In the negative culture group the mean age was 9.8 ± 3.2 years (0.5–17). Medical history for urological disease was negative in all patients. Presenting symptom was scrotal pain in 165 (90.7%), and only three patients (1.6%) had accompanying urinary symptoms. Physical examination was normal besides tender gonad. Urinalysis was completely normal in 169 (92.9%) patients. Scrotal Doppler ultrasound (US) demonstrated non-specific inflammatory process in 146 patients (80%), in nine (5%) torsion of the appendix testis was documented and in 27 (14.8%) scrotal US was normal. Follow up was available in 40% all of whom had an uneventful recovery with normal physical examination. In the positive culture group of 11 patients, the mean age was 11 ± 6.7 years (3 months to 16 years), and eight patients (73%) had a known congenital urological abnormality. Presenting symptom was pain in five (45.4%) and pain with swelling in six (55.6%). Accompanying dysuria, frequency and urgency occurred in eight (72.7%) patients. Urinalysis was abnormal in 10 (90.9%). US demonstrated increased blood flow to the gonad in 10 (90.9%). Conclusions Negative history for urological disease, absence of urinary symptoms and normal urinalysis make the diagnosis of bacterial EO unlikely. In this setting, once testicular torsion was excluded, there is no justification for antimicrobial treatment or further imaging of the urinary tract.

Pregnancy after lower urinary tract reconstruction for congenital abnormalities.

To evaluate the effect of pregnancy on renal function, and the effect of congenital urinary tract abnormality and reconstruction on pregnancy and delivery. The case notes were reviewed of 20 women (median age 32.5 years) who had had 29 live babies. Data collected included patient demographics, congenital urological abnormality, urological reconstructive procedure(s) and any subsequent urological complications. Pregnancy details, including urological and obstetric complications, presentation and mode of delivery, were obtained via a postal questionnaire from the relevant obstetrician. Seven patients had exstrophy-epispadias, seven spinal dysraphism, two sacral agenesis, and one each cerebral palsy, epispadias, imperforate anus and small bladder with vesico-ureteric reflux and congenital incontinence. They had had a mean (range) of 5.7 (1-12) urological reconstructive procedures each. Patients with exstrophy-epispadias had significantly more operations (mean 7.8) than those with spinal dysraphism (mean 4.14) or other diagnoses (mean 2.6) (P < 0.01). At the last follow-up 13 patients had an enterocystoplasty, six a neobladder and one an ileal conduit. Pregnancy-related urological complications were urinary tract infection in 15, upper tract obstruction requiring nephrostomy and stent in three, Mitrofanoff difficulties in two and pyelonephritis in one. There was no significant deterioration in glomerular filtration rate or serum creatinine after pregnancy. Only 10 of the births were normal or assisted vaginal deliveries. Seven patients had emergency and 12 had elective Caesarean sections for obstetric indications, including four breech births in the seven patients with vesical exstrophy. Pregnancy has no long-term effect on renal function and does not compromise reconstruction. Although there is a substantial complication rate and an increased need for Caesarean section, pregnancy in women with lower urinary tract reconstruction for congenital urological abnormalities is ultimately safe for both mother and baby. Interdisciplinary co-operation is desirable for a successful outcome.

Dental management of children with latex allergy.

This paper reviews the aetiology, epidemiology and dental management of children with latex allergy. The issue of latex allergy has serious consequences for the dental management of children with one or more of the following risk factors: spina bifida, atopy, first surgery before one year of age, history of multiple surgical procedures, congenital urologic abnormalities, gastrointestinal malformations, hydrocephalus internus, ventriculo-peritoneal shunts, spinal cord injuries, and family history of atopy. Management of latex allergy is based upon the diligent avoidance of latex exposure. Universal use of powder-free low-allergen latex gloves is recommended.

Angiotensin-converting enzyme genotype distribution in familial vesicoureteral reflux.

Vesicoureteric reflux (VUR) is known to occur in families. In siblings of index patients with VUR, there is a much higher incidence (16% to 46%) than in the general population. The renin-angiotensin system plays an important role in renal development. Recently, it has been reported that angiotensin-converting enzyme (ACE) I/D gene polymorphism is a risk factor for renal parenchymal damage in patients with congenital urological abnormalities. The aim of this study was to investigate the ACE I/D genotype pattern in familial VUR patients. Blood samples were obtained from 86 families in which two or more members had VUR. Samples of DNA were extracted from 407 blood samples (183 affected patients and 224 non-affected family members). To detect ACE I/D polymorphism, polymerase chain reaction (PCR) amplification was performed using specific primers for the ACE gene. PCR products were electrophoresed with 2% agarose gel containing ethidium bromide. Among 224 non-affected family members the ACE genotype distribution of DD, ID, and II was 23%; 56% and 21%, respectively. The ACE genotype distribution of 183 affected patients was 28%, 47% and 25%, respectively. There was no significant difference in ACE I/D distribution between affected patients and their non-affected families. Both the ACE genotype distribution of affected patients and that of non-affected family members were not significantly different from the previously reported genotype distribution of the normal Caucasian population. This study demonstrates that ACE genotype frequencies are similar in index patients with VUR and their unaffected siblings, thus suggesting that the ACE gene is not involved in the development of familial VUR.

Kidney Transplantation in Infants

After completing this article, readers should be able to: 1. Compare and contrast end-stage renal disease in children and adults. 2. Describe the anomalies that may accompany congenital urologic abnormalities. 3. List the primary causes of kidney graft losses in infants. 4. List the common infections encountered posttransplant. Kidney transplantation is the preferred mode of treatment for most children who have end-stage renal disease (ESRD). Despite advances in dialysis management, children who undergo this treatment modality experience stunting in growth and development,1 and mortality rates are higher for children on dialysis compared with those who receive transplants for all age groups.2 In the past, results of kidney transplantation in infants had made the procedure prohibitive, and success rates were extremely low. Compared with adults and larger pediatric patients, infants who have ESRD are at the highest risk for early graft loss and consistently have had the highest mortality rates. Recent advances in the medical and surgical management of these infants have led to improved results in survival and long-term renal transplant function. However, survival rates vary among transplant centers, and the infant subgroup remains the most challenging of any age group receiving transplantation. According to analyses of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) and the United Network of Organ Sharing (UNOS) data, 15% of living donor grafts and 35% of cadaver grafts in infants are lost in the early posttransplant period due to technical complications, vascular thrombosis, or irreversible acute rejection.33,4 Graft survival at 7 years for infants receiving transplantation from living donors (those in whom the best possible outcome is expected) is approximately 71% nationally,4 although results vary. This long-term graft survival is surprisingly high, considering that graft survival at 1 year was only 80% nationally. In our experience with 45 consecutive kidney transplants …

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

The activation of the renin-angiotensin system in various renal disorders is well established. Congenital urological abnormalities, such as obstruction and reflux, are common causes of renal failure in children contributing to approximately 25% of chronic renal failure in this age group. While the outlook relates to the severity of initial renal damage, there is considerable heterogeneity in renal parenchymal destruction among individuals and the reasons for this heterogeneity are not fully understood. A polymorphism within intron 16 of the angiostensin-converting enzyme (ACE) gene has been shown to influence the activity of the renin-angiotensin system, thus, it may also have an impact on the expression of renal disorders. We have determined the incidence of this ID polymorphism of the ACE gene in 47 Kuwaiti children with different urological abnormalities leading to variable degrees of renal impairment and in 48 healthy control subjects with a similar ethnic background. Blood samples were collected from the patients (n = 47) and controls (n = 48), total genomic DNA extracted and the ACE genotypes were determined using a polymerase chain reaction-based method. The DD genotype was detected in 27/47 (57%) cases compared with 25/48 (52%) controls (P = 0.439). The heterozygous genotype ID was found in 14/47 (29%) cases compared with 22/48 (46%) controls (P = 0.0138). The homozygous II genotype was detected in 6/47 (13%) cases compared with 1/48 (2%) controls (P = 0.0247). The D allele of ACE gene was detected in 41/47 (87%) uropathy cases when individuals with homozygous DD and heterozygous ID genotypes were considered collectively. The incidence of parenchymal damage was considerably higher in uropathy cases with DD genotype (62%) compared with those having ID (26%) and II (12%) genotypes. 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.

ACE I/D gene polymorphism predicts renal damage in congenital uropathies.

We investigated angiotensin converting enzyme gene (ACE I/D) polymorphism as a risk for progressive renal damage in congenital uropathies. The ACE I/D genotype was determined in 196 Caucasian patients with congenital uropathies and 163 individuals with no clinical or sonographic evidence of any urological malformations. The study group included patients with ureteropelvic junction obstruction (n=49), primary obstructive megaureter (n=19), primary vesicoureteral reflux (VUR) (n=67), and posterior urethral valves (n=27). Thirty-four patients were excluded because of additional diseases or insufficient follow-up. There was no difference in the ACE I/D distribution between children with uropathies and normal controls (II 16%, ID 56%. DD 28% vs. II 26%, ID 50%, DD 24%). Renal lesions were found in 99 of 162 children by ultrasonography, intravenous pyelography, and nuclear scans. In these children there was significant over-representation of the DD genotype (II 11%, ID 53%, DD 36%) compared with normals (P<0.005, X2=14.9) or with patients with uropathies but no renal lesions (II 23%, ID 62%, DD 15%, P<0.005, X2=14.9). Because ACE I/D has been linked with progressive deterioration of renal function, we evaluated a subset of patients with initially normal kidneys who developed radiographic renal lesions (n=28). Among these patients there was an even greater over-representation of the DD genotype (II 0%, ID 43%, DD 57%, P<0.001, X2=22.6) compared with patients with uropathies but no radiographic lesions. Multivariate analysis revealed that the DD genotype is a risk factor for parenchymal destruction, which was independent of time of diagnosis, surgical intervention, or urinary tract infection. This finding was particularly relevant in patients with VUR who constituted the majority with initially normal kidneys who developed radiographic damage (22/28). Indeed, the odds ratio of developing parenchymal damage with VUR was significantly increased if the individual had the DD genotype (4.2, 95% confidence interval 1.4-13.0). In conclusion the ACE I/D gene polymorphism is a risk factor for renal parenchymal damage in patients with congenital urological abnormalities and appears particularly relevant in children with VUR, where it is an independent predisposing factor.

Angiotensin type 2 receptor is important in the normal development of the ureter.

In humans, the actions of angiotensin II are transduced through the AT1 and AT2 receptors which have recently been implicated in renal organogenesis. Polymorphisms in the human angiotensin II receptor genes have been linked to cardiovascular and nephrological disorders. In this study we evaluated 35 patients with either primary obstructive megaureter or posterior urethral valves. Each was genotyped for the A1166 AT1 polymorphism and the recently described A-1332G AT2 transition. The incidence of these genetic variants was also evaluated in normal controls without any ultrasonographic urological abnormalities. Similar to our previous findings in congenital urological abnormalities, the AT1 receptor genotype distribution did not differ between patients with either primary obstructive megaureter or posterior urethral valves versus controls. In contrast, compared with normal controls, there was a dramatic increase in the occurrence of the AT2 A-1332G transition in patients with primary obstructive megaureter (75.0% vs. 41.9% in controls, P<0.025). In patients with posterior urethral valves, there was no difference in the occurrence of the transition versus controls (36.9%, P=NS). Thus, there is no correlation between the AT1 receptor gene polymorphism and urological abnormalities. However there is an increased incidence in the AT2 genetic variant in patients with primary obstructive megaureter.

Angiotensin II, type 2 receptor in the development of vesico-ureteric reflux.

To investigate if mutation of the angiotensin II (Ang II) receptors AT2 is involved in primary vesico-ureteric reflux (VUR) in humans. Genetic polymorphisms in the AT1 and AT2 receptors was evaluated in 23 patients having the most common congenital urological abnormality, namely primary congenital VUR. The occurrence of the A1166C transition in the AT1 receptor gene and the A-1332G transition in the AT2 receptor gene were evaluated and compared with the incidence in normal controls with no urological abnormalities. The distribution of the AT1 receptor genotypes was no different between patients with VUR and healthy controls. Furthermore, 10 of 23 (44%) patients with VUR and seven of 19 (42%) controls carried the AT2 receptor gene variation. These results contrast with our previous finding of an association between the A-1332G transition in the AT2 receptor gene and primary obstructive megaureter, and pelvi-ureteric junction obstruction. We propose that while the AT2 receptor is crucial for the normal development of the ureter, it does not contribute to the processes which culminate in VUR, which is primarily an abnormality in the bladder trigone.