Congenital Anomalies Of Kidney And Urinary Tract Research Articles

Solitary functioning kidney in children: clinical implications.

ABSTRACTIntroduction:Children with solitary functioning kidney (SFK) are prone to develop long term problems, which are not well represented in the literature. The extent to which the presence of associated congenital anomalies of kidney and urinary tract (CAKUT) further de-stabilize renal function is to be addressed.Objective:This study was conducted to evaluate the etiology, presentation, presence of CAKUT, and renal damage in children with SFK.Methods:All children with SFK who presented to the department of pediatric surgery from March 2014 to May 2016 were included in the study. Children with malignancy were excluded from the study.Results:Of the 20 patients with SFK, 14 (70%) had primary SFK (8 with agenesis and 6 with multicystic dysplastic kidney), 6 (30%) belonged to secondary SFK group, among them 3 had pelviureteric junction obstruction, 2 had posterior urethral valves and 1 had vesicoureteric reflux. Eight (40%) had associated CAKUT, 4 (20%) were asymptomatic while 8 (40%) had UTI and 6 (30%) had hypertension. Ten (50%) patients had reduced glomerular filtration rate (GFR) suggesting compromised renal function.Conclusion:Children with SFK have high morbidity especially when associated with ipsilateral CAKUT. Long-term periodical follow up is essential in these patients to improve clinical outcome.

ULTRASOUND MASS SCREENING OF NEONATES WITH CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT (CAKUT)

Background: Congenital anomalies of kidney and urinary tract represent the most common cause of end stage kidney disease in infant and children. Early detection of these changes allows timely initiation of more specific diagnostic studies, and of therapeutic interventions. Objective: This study was done to detect the incidence and risk factors of (CAKUT) in neonate. Patients and methods: This study was carried out on 390 neonates in the incubator of Al-Matariya Teaching Hospital and Al-Hussein University Hospital during the period from July 2014 to July 2015.All neonates were included except those with apparent congenital anomalies, surgical emergency orinborn errors of metabolism. All neonates after parent consents were subjected to full history, clinical examination and investigated by pelvi-abdominal ultrasound, serum creatinine level, and some cases subjected to more investigations in the form of computed tomography scan with intravenous urographin contrast medium, ascending cystourethrography and TC 99m DTPA dynamic renal scan. Results: The overall incidence of congenital anomalies of kidney and urinary tract was 3.3%. Positive family history of renal anomalies together with maternal history of diabetes mellitus and maternal age above 35 years were considered predictors for renal anomalies by binary logistic regression. Conclusion: Congenital anomalies of kidney and urinary tract (CAKUT) were major health issues and were the leading cause of ESRD in pediatric population.

Whole-exome sequencing in the molecular diagnosis of individuals with congenital anomalies of the kidney and urinary tract and identification of a new causative gene.

PurposeTo investigate the utility of whole-exome sequencing (WES) to define a molecular diagnosis in patients clinically diagnosed with congenital anomalies of kidney and urinary tract (CAKUT).MethodsWES was performed in 62 families with CAKUT. WES data were analyzed for Single Nucleotide Variants (SNVs) in 35 known CAKUT genes, putatively deleterious sequence changes in new candidate genes, and potentially disease-associated copy-number variants (CNVs).ResultsIn approximately 5% of families, pathogenic SNVs were identified in PAX2, HNF1B, and EYA1. Observed phenotypes in these families expand the current understanding about the role of these genes in CAKUT. Four pathogenic CNVs were also identified using two CNV detection tools. In addition, we found one deleterious de novo SNV in FOXP1 among the 62 families with CAKUT. Database of clinical BMGL laboratory was queried and seven additional unrelated individuals with novel de novo SNVs in FOXP1 were identified. Six of these 8 individuals with FOXP1 SNVs, have syndromic urinary tract defects, implicating this gene in urinary tract development.ConclusionWe conclude that WES can be used to identify the molecular etiology (SNVs, CNVs) in a subset of individuals with CAKUT. WES can also help identify novel CAKUT genes.

Copy number variations in multicystic dysplastic kidney: update for prenatal diagnosis and genetic counseling.

To assess the clinical implication of chromosomal microarray analysis (CMA) in prenatal diagnosis of MCDK. Thirty-seven cases with MCDKs detected by prenatal ultrasound were enrolled in the study; 33 cases were isolated MCDKs and four cases were non-isolated MCDKs. CMA was performed on the Affymetrix CytoScan HD platform. The frequencies of the detected CNVs were compared with 461 cases that underwent CMA for anomalies unrelated to congenital anomalies of kidney and urinary tract (CAKUT) or 124 healthy newborns as controls. All of the annotated CNVs were validated by MLPA or qPCR. Pathogenic CNVs were detected in 13.5% (5/37) of MCDKs. Two 17q12 deletions, one untypical 22q11.2 deletion, and one 22q11.2 duplication were detected in four isolated MCDK cases. Duplication of 1q31.3q44 was identified in a non-isolated MCDK case. Three of the five pathogenic CNVs were inherited. We also validated eight CNVs of uncertain significance only detected in MCDKs and five CNVs with higher frequency in MCDKs. A substantial proportion of MCDKs were associated with pathogenic CNVs. Family members with the same CNV were asymptomatic or of different kind of renal malformations. It may be reasonable to perform CMA when MCDKs are identified prenatally. © 2016 John Wiley & Sons, Ltd.

Associated nonurinary congenital anomalies among infants with congenital anomalies of kidney and urinary tract (CAKUT)

Infants with congenital anomalies of kidney and urinary tract (CAKUT) often have other associated anomalies. The purpose of this investigation was to assess the prevalence and the types of associated anomalies in CAKUT in a defined population from northeastern France. The associated anomalies in CAKUT were collected in all livebirths, stillbirths and terminations of pregnancy during 26 years in 346,831 consecutive births of known outcome in the area covered by our population based registry of congenital anomalies. Of the 1678 infants with CAKUT born during this period (prevalence at birth of 48.4 per 10,000), 563 (34%) had associated anomalies. There were 119 (7%) patients with chromosomal abnormalities including 33 trisomies 18 (2%), and 168 (10%) nonchromosomal recognized dysmorphic conditions. There were no predominant recognized dysmorphic conditions, but VA(C)TER(L) association (3%). However, other recognised dysmorphic conditions were registered including Meckel–Gruber syndrome (2%), and prune belly syndrome (1%). Two hundred seventy six (16%) of the patients had multiple congenital anomalies, non syndromic, non chromosomal (MCA). Anomalies in the musculoskeletal, the digestive, the cardiovascular and the central nervous systems were the most common other anomalies. Prenatal diagnosis was obtained in 71% of dysmorphic syndromes with CAKUT. In conclusion the overall prevalence of associated anomalies, which was one in three infants, emphasizes the need for a thorough investigation of infants with CAKUT. The most commonly associated major nonurinary anomalies involved the musculoskeletal system, followed by the digestive, the cardiovascular and the central nervous systems. A routine screening for other anomalies may be considered in infants and in fetuses with CAKUT. One should be aware that the anomalies associated with CAKUT can be classified into a recognizable anomaly syndrome or pattern in one out of six infants with CAKUT.

Congenital anomalies of kidney and urinary tract (CAKUT)

Abstract Congenital abnormalities of kidney and urinary tract are the leading cause of end-stage kidney disease in children. These result from genetic as well as environmental causes. The embryology of kidney and urinary tract is modified by genetic mutations leading to CAKUT. These anomalies may occur in isolation or as a part of syndrome with renal as well as non-renal manifestations. The phenotype may vary from asymptomatic abnormalities on one hand to renal agenesis on the other. Lower tract abnormalities are frequently associated. Many of the disorders may be diagnosed antenatally on imaging. Proper antenatal and post-natal management may prevent progression to ESKD. The role of genetics in diagnosis remains unclear at present and needs further evaluation.

Clinical importance of pyelocalyceal dilation diagnosed by postnatal ultrasonographic screening of the urinary tract

BackgroundUltrasonographic (US) screening of the urinary tract (UT) in infants was used to determine if there is a connection between the frequency of pyelocaliceal dilation (PCD) in asymptomatic infants with normal antenatal US screening and occurrence of congenital anomalies of kidney and urinary tract (CAKUT) and urinary tract infections (UTI).Material/MethodsUS screening of the UT was performed on 1000 healthy infants, 7 days to 6 months old. Two subgroups of kidneys were described: subgroup 1 contained kidneys with anterior posterior pelvic diameter (APPD) of 5–9.9 mm, and subgroup 2 with APPD over 10 mm. US examinations and methods for detection of UTI and CAKUT were used.Results PCD was found in 74 infants (7.4%): 1.9% of infants had CAKUT, and 8.4% had UTI. In subgroup 1, CAKUT was found in 4 (6.3%) and UTI in 9 (14.3%) infants. In subgroup 2, CAKUT was found in 6 (54.5%), and UTI in 4 (36.4%) infants.ConclusionsMild PCD significantly increases the risk for CAKUT but not for UTI. Moderate to severe PCD significantly increases risk for both CAKUT and UTI. The postnatal US screening of UT is recommended for improved detection of PCD and associated CAKUT. Indirectly, postnatal US screening of UT can help in detecting people at risk for UTI in the first year of life, and therefore help prevent possible kidney damage.

Congenital anomalies of kidney and urinary tract in siblings: An uncommon condition

Congenital anomalies of kidney and urinary tract (CAKUT) are important causes of chronic kidney disease (CKD) in childhood. Most do not have a definite identifiable genetic defect and occur in isolation. Rarely, familial occurrence of CAKUT has been reported. The burden of CKD to a family in a developing country is enormous, and if more than one child is afflicted with the condition, the situation is almost catastrophic. We present here two families with siblings having upper and lower urinary tract obstruction.

Nierentransplantation im Kindesalter – Behandlungsmethode der Wahl bei terminaler Niereninsuffizienz

Die Nierentransplantation ist die bevorzugte Behandlungsmethode bei terminaler Niereninsuffizienz im Kindes– und Jugendalter. Sie wird in Deutschland jährlich zirka 120–mal durchgeführt. Die häufigsten zugrunde liegenden Erkrankungen der Patienten sind angeborene Anomalien der Nieren und ableitenden Harnwege. Mit einer immunsuppressiven Dreifachtherapie aus Calcineurininhibitor, Steroid und Mykophenolatmofetil wird heute ein 1–Jahres–Transplantatüberleben von über 90 % erreicht. Das Langzeittransplantat– und Patientenüberleben werden durch chronische Transplantatdysfunktion und Komorbiditäten wie kardiovaskuläre Erkrankungen und Infektionen beeinflusst. Die umfassende Betreuung von kindlichen Transplantatempfängern und deren Familien sowie der geordnete Transfer von Jugendlichen in die Erwachsenenmedizin sind nur in einem spezialisierten kindernephrologischen Zentrum möglich.

Children's toxicology from bench to bed - Drug-induced Renal Injury (1): The toxic effects of ARB/ACEI on fetal kidney development

Development of fetal kidney is a finely programmed sequence, and is regulated by many important molecules. The perturbation of normal kidney development leads to congenital anomalies of kidney and urinary tract (CAKUT). CAKUT includes hypoplastic/dysplastic kidney, obstructive nephropathy and several other anomalies. CAKUT is of clinically importance, since it could lead to end stage renal failure when its anomaly grade is severe. So far, several causative genes responsible for development of CAKUT have been identified, including genes encoding molecules related to the renin-angiotensin-aldosterone system, RAS system. In humans, maternal administration of agents with inhibitory effects on the RAS system, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin type 1 receptor blockers (ARBs), have been reported to cause severe renal malformation, designated as ACEI/ARB fetopathy. In this paper, we overview the development of fetal kidney and address the effects of ACEIs/ARBs on fetal kidney.

A Locus for Renal Malformations Including Vesico-Ureteric Reflux on Chromosome 13q33–34

Congenital anomalies of kidney and urinary tract (CAKUT), including vesico-ureteric reflux (VUR), are major causes of ESRD in childhood. Herein is reported evidence for a locus on 13q33q34 associated with CAKUT. Deletion mapping of chromosome 13q was performed in four children with CAKUT using 31 microsatellite markers on peripheral blood genomic DNA that was obtained from the patients and their parents. mRNA expression of the positional candidate genes was compared with sequences in electronic databases in silico and also studied in adult and fetal mouse kidneys using reverse transcription-PCR. The children (three girls; age range 5 to 17 yr) had varying severity of developmental delay and other organ system involvement. The spectrum of CAKUT included high-grade VUR (n = 2), renal dysplasia (n = 2), and hydronephrosis (n = 1). Both the children with VUR had evidence of renal failure with one of them developing ESRD. Deletion mapping identified a 7-Mb critical region flanked by markers D13S1311 and D13S285. There are 33 genes (12 known; 21 computer predicted) in this region. In silico expression studies showed matches for 14 of these genes in the kidneys and 10 in the bladder expressed sequenced tags databases. Mouse kidney studies showed that of the 24 genes examined, several had variable expression through the different stages of renal development, whereas five of the genes were not expressed at all. Herein is reported a new locus on chromosome 13q33q34 that can be associated with VUR with several genes showing mRNA expression patterns that suggest their potential for involvement in renal/urinary tract developmental anomalies.

Steroid-resistant nephrotic syndrome and congenital anomalies of kidneys: Evidence of locus on chromosome 13q

Steroid-resistant nephrotic syndrome (SRNS) and congenital anomalies of kidney and urinary tract (CAKUT) are major causes of renal dysfunction in children. Although a few patients with 13q deletion have been previously reported with renal anomalies, the association of SRNS with 13q has not been reported and critical regions associated with CAKUT have not been identified. We present the results of deletion mapping studies to identify the critical regions. Cytogenetic and deletion mapping studies were performed on DNA obtained from peripheral blood of two children with renal anomalies and interstitial deletion of 13q as well as their parents. Twenty eight microsatellite markers with a spacing of 1-8 Mb (1-3 cM) were utilized. The patients (both males, 5 and 10 years old) had varying severity of developmental delay and other neurologic disorders. The renal involvement included hydronephrosis, ureterocele, renal dysplasia, and mesangioproliferative SRNS. Our studies imply existence of at least two critical regions in the 13q area that are linked to CAKUT. The first is a 7 Mb region defined by markers D13S776 and D13S891 shared by both patients. The second is a much larger region extending at least 33 Mb above D13S776 seen in one patient with severe renal malformations and SRNS. We report an association of chromosome 13q with CAKUT as well as SRNS. Our studies suggest the presence of more than one gene in this region that is likely to be involved in renal development and function.