Kidney Malformations Research Articles

A clinical case of surgical treatment of calyx diverticulum in a 12-year-old child

Introduction. Calyx diverticulum is a rather rare pathology in pediatric practice. In the structure of cystic kidney malformations, it amounts up to 12-15%. In most cases, the disease is asymptomatic. To make a differential diagnostics and to define a technique for surgical treatment, computed tomography or magnetic resonance imaging are used. Currently, puncture-sclerotic method and endosurgical (laparoscopic, retroperitoneoscopic) one can be successfully applied. The main purpose of this clinical observation is to illustrate that little-traumatic laparoscopic access to the kidney and plasma ablation of the diverticulum epithelial lining can be used to have successful outcomes.Material and methods. The authors describe a clinical case of renal cavities in a 12-year-old boy - calyx diverticulum of the right kidney and a cyst of the left kidney - which were successfully treated with a combined approach when puncture and laparoscopic corrections were used depending on lesion’s chracteriatics.Conclusion. A rational approach and substantiation of the applied surgical technique with plasma ablation of calyx diverticulum cavity allowed to obtain good results - cavity size was reduced and renal parenchyma was preserved what is important for future organ functioning.

Nephroprotective Role of Zhibai Dihuang Wan in Aristolochic Acid-Intoxicated Zebrafish.

Zhibai Dihuang Wan (ZDW) is an eight-herbal formula of traditional Chinese medicine. Clinically, it regulated immune activity and was used to treat diabetes and renal disease. In this study, we aimed to explore the nephroprotective effect of ZDW in an aristolochic acid- (AA-) intoxicated zebrafish model. We used a green fluorescent kidney transgenic zebrafish to evaluate the nephroprotective effects of ZDW by recording subtle changes in the kidney. Our results demonstrated that ZDW treatment can attenuate AA-induced kidney malformations (60% for AA-treated, 47% for pretreatment with ZDW, and 17% for cotreatment ZDW with AA, n = 50). Furthermore, we found that the expression levels of tnfα and mpo were decreased either in pretreatment or cotreatment groups. In conclusion, our findings revealed that AA-induced nephrotoxicities can be attenuated by ZDW. Therefore, we believe that zebrafish represent an efficient model for screening AA-protective Chinese medicine.

Improvement of prenatal diagnosis of bilateral renal agenesis in a fetus

Objective: to identify the most practical method for diagnosing bilateral renal agenesis in a fetus during prenatal ultrasound screening. Material and methods. The study included the results of ultrasound screening of 50 fetuses, which initially, were presumptively diagnosed with bilateral renal agenesis using the generally accepted method of ultrasound screening. The sonographic characteristics and visualization features of the structures of the urinary system of the fetuses were analyzed. Results. The sensitivity indices of the basic methods for diagnosing bilateral renal agenesis in a fetus (87.5 %), specificity (93 %) and general accuracy (92.2 %) have been determined; a method for prenatal diagnosis of bilateral renal agenesis in a fetus has been developed, which consists in assessing the possibility of ultrasound imaging of the fetal bladder after an administration of furosemide to the pregnant patient, which has increased the sensitivity and specificity of the method up to 100 %. Conclusion. The developed method of prenatal diagnosis of bilateral renal agenesis in a fetus, which consists in assessing the possibility of ultrasound imaging of the fetal urinary bladder after an administration of furosemide to the pregnant patient, improves the quality of the diagnosis of congenital malformations of the fetal kidneys and minimizes unreasonable psychoemotional stress in the pregnant patient resulting from the false positive diagnosis, which is a fundamental question for appropriateness of prolongation of her pregnancy.

Prenatal diagnosis of 22q11.2 copy number abnormalities in fetuses via single nucleotide polymorphism array

The q11.2 region on chromosome 22 contains numerous low-copy repeats that lead to deleted or duplicated regions in the chromosome, thereby resulting in different syndromes characterized by intellectual disabilities or congenital anomalies. The association between patient phenotypes and 22q11.2 copy number abnormalities has been previously described in postnatal cases; however, these features have not been systematically evaluated in prenatal cases because of limitations in phenotypic identification in prenatal testing. In this study, we investigated the detection rate of 22q11.2 copy number abnormalities in 2500 fetuses using single nucleotide polymorphism (SNP) array and determined the common abnormal ultrasound findings in fetuses carrying the 22q11.2 copy number abnormalities. The 22q11.2 copy number abnormalities were identified in 13 fetuses with cardiovascular malformations (6/13), kidney malformations (3/13), isolated ultrasound markers (3/13), or high-risk Down syndrome based on maternal serum screening (1/13). Approximately 0.5% (13/2500) of the fetuses harbored 22q11.2 copy number abnormalities. The most frequent ultrasound findings in fetuses with these abnormalities were cardiovascular malformations, followed by kidney malformations and isolated ultrasound markers. Prenatal diagnosis of these genetic abnormalities allows for the delineation of differential diagnoses, characterization of a wide spectrum of associated malformations, and determination of associations that exist between prenatal diagnosis and obstetrical outcomes.

Transforming growth factor beta signaling functions during mammalian kidney development.

Aberrant transforming growth factor beta (TGFβ) signaling during embryogenesis is implicated in severe congenital abnormalities, including kidney malformations. However, the molecular mechanisms that underlie congenital kidney malformations related to TGFβ signaling remain poorly understood. Here, we review current understanding of the lineage-specific roles of TGFβ signaling during kidney development and how dysregulation of TGFβ signaling contributes to the pathogenesis of kidney malformation.

Intrauterine Growth Restriction and Risk of Diverse Forms of Kidney Disease during the First 50 Years of Life.

Previous studies have shown that individuals with low birth weight (LBW) or small for gestational age (SGA) have higher risk of kidney failure. This study investigates birth-related exposures and risk of CKD and other kidney diagnoses. The Medical Birth Registry of Norway has registered extensive medical data on all births in Norway since 1967. The Norwegian Patient Registry has registered diagnostic codes for all admissions and outpatient visits to Norwegian hospitals since 2008. Data from these registries were linked, and risk of CKD and other groups of kidney disease were analyzed using logistic regression statistics. LBW (below the tenth percentile), SGA (birth weight below the tenth percentile for gestational age), and preterm birth (<37 weeks) were analyzed as exposures. A total of 2,663,010 individuals were included. After a mean follow-up of 26 years (maximum 50 years), 4495 had been diagnosed with CKD and 12,818 had been diagnosed with other groups of kidney disease. LBW was associated with an odds ratio (OR) for CKD of 1.72 (95% confidence interval [95% CI], 1.60 to 1.90), SGA with an OR of 1.79 (95% CI, 1.65 to 1.94), and preterm birth with an OR of 1.48 (95% CI, 1.33 to 1.66). Analyses using diagnosis of CKD at stages 3-5 as end point showed similar results. Results were similar for men and women. We analyzed adjusted ORs for other groups of kidney disease and found that LBW was associated with an adjusted OR of 1.44 (95% CI, 1.33 to 1.56) for acute kidney disease, 1.24 (95% CI, 1.14 to 1.36) for GN, 1.35 (95% CI, 1.17 to 1.56) for cystic kidney disease, and 1.15 (95% CI, 1.06 to 1.25) for kidney disease resulting from kidney or urinary tract malformations. LBW, SGA, and preterm birth are associated with higher risk of CKD in the first 50 years of life. Risk of other groups of kidney disease was less pronounced. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_17_CJN04080320.mp3.

SLC20A1 Is Involved in Urinary Tract and Urorectal Development.

Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.

Birth Defects Data From Population-Based Birth Defects Surveillance System in a District of Southern Jiangsu, China, 2014-2018.

As a population-based national surveillance region, Tianning District confronts with great challenges in birth defects (BDs) prevention. We aimed to describe the epidemiology of BDs in infants (including dead fetus, stillbirth, or live birth between 28 weeks of gestation and 42 days after birth) in Tianning District from 2014 to 2018. The data was collected from the national birth defect surveillance system. The prevalence rates of BDs were calculated by poisson distribution. Trends of incidence and the associations of regarding perinatal characteristics with BDs were analyzed by poisson regression. During the study period, the prevalence of BD was 155.49 per 10,000 infants. The ten leading BDs were congenital heart defects (CHD), polydactyly, Congenital malformation of kidney (CMK), syndactyly, cleft palate, hypospadias, Congenital hypothyroidism (CH), congenital atresia of rectum and anus, congenital talipes equinovarus (CTE), and microtia. A significant increase in the prevalence of CHD was observed with a prevalence rate ratio (PRR) of 1.191. Gravidity ≥ 3 (PRR = 1.38) and multiple births (PRR = 2.88) were risk factors for BDs. Premature delivery (PRR = 4.29), fetal death or stillbirth (PRR = 24.79), and infant death (PRR = 43.19) were adverse consequences of BDs. Strengthening publicity and education, improving the ability of diagnosis and monitoring, expanding surveillance time quantum of BDs system may be warranted.

Aberrant Differentiation of Human Pluripotent Stem Cell-Derived Kidney Precursor Cells inside Mouse Vascularized Bioreactors

Background: Numerous studies have documented the in vitro differentiation of human pluripotent stem cells (hPSCs) into kidney cells. Fewer studies have followed the fates of such kidney precursor cells (KPCs) inside animals, a more life-like setting. Here, we tested the hypothesis that implanting hPSC-derived KPCs into an in vivo milieu surgically engineered to be highly vascular would enhance their maturation into kidney tissues. Methods: 3D printed chambers containing KPCs were implanted into the thighs of adult immunodeficient mice. In some chambers, an arterial and venous flow-through (AVFT) was surgically fashioned. After 3 weeks and 3 months, implants were studied by histology, using qualitative and quantitative methods. Results: After 3 weeks, chambers containing AVFTs were richer in small vessels than contralateral chambers without AVFTs. Glomeruli with capillary loops and diverse types of tubules were detected in all chambers. At 3 months, chambers contained only rudimentary tubules and glomeruli that appeared avascular. In chambers with AVFTs, prominent areas of muscle-like cells were also detected near tubules and the abnormal tissues immunostained for transforming growth factor β1. These features have similarities to renal dysplasia, a typical histological signature of human congenital kidney malformations. Conclusions: This study urges a note of caution regarding the in vivo fates of hPSC-derived kidney precursors, with pathological differentiation appearing to follow a period of increased vascularity.

Childhood Urinary Tract Infections and Pregnancy-Related Complications in Adult Women.

Long-term outcomes of urinary tract infection (UTI) in childhood are not well known. Pregnancy may reveal latent renal damage caused by a UTI because of stress on the kidneys. Our cohort included adult women with an ultrasonography taken because of a childhood UTI in 1981-1991 (N = 1175). Nine women with a severe congenital kidney malformation or urinary tract obstruction were excluded. Altogether, 260 mothers with a childhood UTI and 500 population-based control mothers without a childhood UTI matched for age, and delivery dates were compared. Our primary end point was the proportion of women with essential or gestational hypertension, preeclampsia, proteinuria, or pyelonephritis during the first pregnancy. The pregnancy outcomes of the women with a UTI in childhood did not differ from those of the controls because 105 of 260 (40%) patients met the primary end point compared with 204 of 500 (41%) controls (relative risk [RR] 0.99; 95% confidence interval [CI] 0.82 to 1.2; P = .91). Similarly, there were no significant differences between the 2 groups in essential hypertension (RR 1.0; 95% CI 0.65 to 1.6; P = .92), gestational hypertension (RR 0.93; 95% CI 0.74 to 1.2; P = .54), preeclampsia (RR 1.5; 95% CI 0.91 to 2.5; P = .11), proteinuria (RR 1.2; 95% CI 0.81 to 1.8; P = .36) or pyelonephritis (2 controls and none of the patients; P = .55) during the first pregnancy. Childhood UTIs did not increase the risk of pregnancy-related complications in this controlled population-based study. Thus, UTIs in childhood without severe urinary tract abnormalities appear to have a minimal effect on kidney health in early adulthood.

Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations

Ligase IV (LIG4) syndrome is a rare disorder of DNA damage repair caused by biallelic, pathogenic variants in LIG4. This is a phenotypically heterogeneous condition with clinical presentation varying from lymphoreticular malignancies in developmentally normal individuals to significant microcephaly, primordial dwarfism, radiation hypersensitivity, severe combined immunodeficiency and early mortality. Renal defects have only rarely been described as part of the ligase IV disease spectrum.We identified a consanguineous family where three siblings presenting with antenatal growth retardation, microcephaly, severe renal anomalies and skeletal abnormalities, including radial ray defects. Autozygosity mapping and exome sequencing identified a novel homozygous frameshift variant in LIG4, c.597_600delTCAG, p.(Gln200LysfsTer33), which segregated in the family. LIG4 is encoded by a single exon and so this frameshift variant is predicted to result in a protein truncated by 678 amino acids. This is the shortest predicted LIG4 protein product reported and correlates with the most severe clinical phenotype described to date. We note the clinical overlap with Fanconi anemia and suggest that LIG4 syndrome is considered in the differential diagnosis of this severe developmental disorder.

DIAGNOSTICS AND TREATMENT OF CHOLEDOCHAL CYSTS IN CHILDREN

Introduction. Cysts of the common bile duct or choledoch cysts (CC) are congenital cystic dilatation of the extrahepatic and / or intrahepatic bile ducts. The etiology is not fully clear, but it has been proven that abnormal pancreatobiliary anastomosis plays a major role in CC formation. Clinical manifestations range from prolonged jaundice in newborns to non-specific abdominal pains in older patients. Purpose. To study clinical manifestations of common bile duct cysts in children of different age, to define diagnostic criteria as well as to analyze outcomes after surgical treatment. Material and methods. In 2001-2019, 27 patients with chronic obstructive CC, aged from several days to 12 y.o., were treated in the Children’s City Multidisciplinary Clinical Specialized Center for High Medical Technologies of St. Petersburg. Most of them (16-59.2%) had CC of type IA by the Todani classification. Ultrasound examination and MRI cholangiography were used for diagnostics. Children with CC of type V (Caroli disease) required a specific approach to their treatment because of the combined malformations in kidneys (polycystic kidney disease); in 19 patients with CC of types I and IV the cystically altered choledoch was resected and hepaticojejunostomy was put on the loop by the P technique. Results. 19 patients were operated on. Good outcomes were in 15 cases. Underlying disease complications in the preoperative period were noted in 8 patients: pancreatitis in 5 patients, perforation of cysts with biliary peritonitis in 3 patients. In the postoperative period, 4 patients had complications: stenosis of the anastomosis in 1; portal hypertension in 1; 3 children developed cholangitis, 1 of them required surgical correction. Out of 5 patients with Caroli disease, 2 children died in the neonatal period, one because his parents refused of treatment. Two children aged 12 and 17 had liver and kidney transplantation. Conclusion. CC clinical manifestations are diverse; asymptomatic course can develop up to some age. Ultrasound and MRI cholangiography are main diagnostic tools. Resection of the cyst with hepaticojejunostomy on the loop by the P technique is a radical approach to the treatment and has good outcomes. Patients with Caroli disease require an individual approach.

P0767INTRAUTERINE GROWTH RESTRICTION AND RISK OF KIDNEY DISEASE DURING THE FIRST 50 YEARS OF LIFE

Abstract Background and Aims Previous studies have shown that Low Birth Weight (LBW) and small for gestational age (SGA) are associated with increased risk of end-stage renal disease. Few population-based studies have however investigated risk of less severe kidney disease and in the present study, we investigate risk of chronic kidney disease and other kidney disease diagnoses. Method The Norwegian Patient Registry (NPR) has registered ICD diagnostic codes for all admissions and outpatient visits to Norwegian hospitals since 2008 (available for 2008-2016 in this study). The Norwegian Medical Birth Registry (MBR) has registered birth weight, gestational age and several other data on maternal and offspring health for all birth in Norway since 1967. Data from these registries were linked and risk of chronic kidney disease (CKD) and other groups of kidney disease were analyzed with logistic regression statistics. LBW (less than the 10th percentile), SGA (less than the 10th percentile) and preterm birth (less than 37 weeks) were analyzed as risk markers. Adjusted analyses were performed for the main analyses by including birth year, gender, maternal disease, maternal preeclampsia, maternal marital status and malformations in the newborn. Results Of the 2,663,010 included individuals, 4,495 had been diagnosed with CKD and 12,818 with acute kidney disease, glomerulonephritis, hereditary kidney disease or kidney disease due to kidney or urinary tract malformations. LBW was associated with an adjusted odds ratio (aOR) for CKD of 1.61 (1.48-1.74), SGA with an aOR of 1.51 (1.39-1.63) and preterm birth with an aOR of 1.47 (1.31-1.66). As compared to subjects with none of these risk factors (LBW, SGA or preterm birth), subjects with only one risk factor had an aOR of 1.49 (1.35-1.66), subjects with 2 risk factors had adjusted aOR of 1.72 (1.57-1.88) and subjects with 3 risk factors had aOR of 2.56(1.99-3.29). Analyses of chronic kidney disease stage 3, 4 and 5 showed similar results. There were no significant gender differences. We further analysed aOR for other groups of kidney disease and found that LBW was associated with aOR of 1.52 (1.40-1.65) for acute kidney disease, 1.26 (1.16-1.38) for glomerulonephritis, 1.55 (1.34-1.80) for hereditary kidney disease and 1.38 (1.27-1.49) for kidney disease due to kidney or urinary tract malformations; analyses for the other risk factors showed similar results. Conclusion LBW and SGA are strong risk factors for diagnosis of all stages of CKD during the first 50 years of life and the risks seem to be increased also for other groups of kidney disease. Our results underline the public health importance of LBW and SGA.

GREB1L variants in familial and sporadic hereditary urogenital adysplasia and Mayer-Rokitansky-Kuster-Hauser syndrome.

Congenital uterine anomalies (CUA) may have major impacts on the health and social well-being of affected individuals. Their expressivity is variable, with the most severe end of the spectrum being the absence of any fully or unilaterally developed uterus (aplastic uterus), which is a major feature in Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH). So far, etiologies of CUA remain largely unknown. As reports of familial occurrences argue for strong genetic contributors in some cases, we performed whole exome sequencing in nine multiplex families with recurrence of uterine and kidney malformations, a condition called hereditary urogenital adysplasia. Heterozygous likely causative variants in the gene GREB1L were identified in four of these families, confirming GREB1L as an important gene for proper uterine and kidney development. The apparent mode of inheritance was autosomal dominant with incomplete penetrance. The four families included fetuses with uterovaginal aplasia and bilateral renal agenesis, highlighting the importance to investigate GREB1L in such phenotypes. Subsequent sequencing of the gene in a cohort of 68 individuals with MRKH syndrome or uterine malformation (mostly sporadic cases) identified six additional variants of unknown significance. We therefore conclude that heterozygous GREB1L variants contribute to MRKH syndrome and this probably requires additional genetic or environmental factors for full penetrance.

Behavioural effects of extracellular matrix protein Fras1 depletion in the mouse.

Fras1 is an extracellular protein of the basement membranes that surround embryonic epithelia, choroid plexuses and meninges in foetal mouse brain. Depletion of Fras1 in knockout mice results in sub-epidermal blistering and fusion of eyelids and digits as well as malformation of lungs and kidneys. Mutations in the human counterpart FRAS1 are responsible for the Fraser Syndrome with clinical manifestations similar to the murine phenotype. In addition, brain deformities or mental impairments have occasionally been reported in patients with Fraser Syndrome. In the present study, we explored the possible involvement of Fras1 in brain function, analysing its expression pattern in mouse brain and investigating aspects of Fras1-/- mice behaviour, related to the function of brain regions expressing Fras1. Transcripts were detected in choroid plexuses and in certain brain regions including cortical, hippocampal and amygdalar areas in juvenile mice. Behavioural tests revealed that Fras1-/- mice exhibit impaired egocentric spatial memory, aberrant olfactory learning and memory, markedly reduced fear memory in an auditory fear conditioning task, as well as reduced anxiety expression in open field and elevated plus maze tests. Moreover, the extracellular matrix organization has been severely affected in cortical and subcortical areas as demonstrated by Wisteria floribunda agglutinin immunolabelling. The widespread detection of Fras1 transcripts in the brain of both pre- and postnatal mice, as well as the behavioural and cellular disturbances exhibited by Fras1-/- adult mice provide evidence for the involvement of Fras1 in brain organization and function.

A young girl with right ovarian torsion and left ovarian ectopy

BackgroundMayer-Rokitansky-Küster-Hauser (MRKHS) syndrome refers to congenital hypoplasia/aplasia of the uterus, the cervix and the upper 2/3 of the vagina, in females with normal ovaries and fallopian tubes, secondary sexual characteristics and 46 XX karyotype. This condition originates from abnormal development of Müller’s paramesonephric ducts in the early stages of embryonic development. Kidney agenesis or malformations are the most commonly associated with unilateral kidney agenesis. Ovaries may be ectopic in 16–19% of MRKHS patients. Primary amenorrhoea, due to the absence of the uterus, is the most common presentation. Female karyotype confirmation is mandatory to differentiate it from complete androgen insensitivity syndrome and 17-alpha-hydroxylase deficiency. The management of MRKHS is multidisciplinary in order to encompass psychological, medical and surgical issues.Case presentationA four-year-old girl, presented to the emergency department complaining of left groin swelling noted 2 days earlier. The patient had recently been evaluated for an episode of acute abdominal pain and vomiting, with a final diagnosis of right ovarian torsion. At that time, the ultrasound imaging was not able to identify the left kidney, the left ovary and uterus. Surgical abdominal exploration confirmed the right ovarian torsion and was not able to identify the left kidney and the left ovary. Only a remnant of the uterus was present. Therefore, the right ovary was removed, and a diagnosis of MRKHS was made. Ultrasound imaging showed a left inguinal hernia. The hernial sac consisted of a solid oval vascularized formation suggestive of an annexe. The patient underwent a surgical procedure to correct the left inguinal hernia. In the operating setting, the presence of a vascularized, ectopic ovary carrying the tuba inside the hernial sac was observed.ConclusionsIn front of a patient with ovarian torsion and anatomical features suggestive of MRKHS, both the ovaries should always be searched for, with a high suspicion threshold for extrapelvic ovary. Identifying the ectopic ovary, in this case, helped to preserve patient fertility, avoiding a possible torsion.

Clinical Integration of Genome Diagnostics for Congenital Anomalies of the Kidney and Urinary Tract.

Revolutions in genetics, epigenetics, and bioinformatics are currently changing the outline of diagnostics and clinical medicine. From a nephrologist's perspective, individuals with congenital anomalies of the kidney and urinary tract (CAKUT) are an important patient category: not only is CAKUT the predominant cause of kidney failure in children and young adults, but the strong phenotypic and genotypic heterogeneity of kidney and urinary tract malformations has hampered standardization of clinical decision making until now. However, patients with CAKUT may benefit from precision medicine, including an integrated diagnostics trajectory, genetic counseling, and personalized management to improve clinical outcomes of developmental kidney and urinary tract defects. In this review, we discuss the present understanding of the molecular etiology of CAKUT and the currently available genome diagnostic modalities in the clinical care of patients with CAKUT. Finally, we discuss how clinical integration of findings from large-scale genetic, epigenetic, and gene-environment interaction studies may improve the prognosis of all individuals with CAKUT.

Congenital Hepatic Fibrosis in Children and Adults: Clinical Manifestations, Management, and Outcome-Case Series and Literature Review.

Background Congenital hepatic fibrosis is a hereditary fibropolycystic disease caused by ductal plate malformation. It is characterized by portal hypertension, but the manifestations, management, and outcome vary in children and adults. To raise awareness of medical staff, we have comprehensively compared the clinical features of congenital hepatic fibrosis between children and adults. Methods We retrospectively enrolled all patients diagnosed with congenital hepatic fibrosis at the Huashan Hospital from August 2015 to August 2017 and analyzed their familial, clinical, laboratory, imaging, treatment, and follow-up data in detail. In addition, we reviewed cases with congenital hepatic fibrosis reported in the past 20 years in China and analyzed them according to the patients' age. Results A total of eight patients were diagnosed with congenital hepatic fibrosis in the study, including four children and four adults. The onset age of the children, who suffered from severe complications of portal hypertension and needed liver transplantation, ranged from 1 to 15 years old. The disorder developed in adults aged 26 to 60 years old. Three adults complained of recurrent abnormal liver function at the onset of illness, and they mainly received conservative treatments. The literature review included 30 children and 33 adults. In comparison, hepatomegaly was more common in children than in adults (57% vs. 21%, p = 0.004). Malformation of kidneys and bile duct abnormalities were common, and multisystem involvement included eyes, other digestive organs, and genital and central nervous systems. Conclusions Serious complications of portal hypertension developed in children requiring liver transplantation, while adults often had mild-to-moderate liver injuries upon onset. Adults with CHF varied a lot in clinical manifestations. Multiorgan involvement and unusual course are helpful to make a diagnosis. Timely histological assessment by liver biopsy and multidisciplinary cooperation are crucial for definitive diagnosis and early intervention.

Copy number variations associated with fetal congenital kidney malformations

BackgroundCongenital anomalies of the kidney and urinary tract (CAKUT) constitute 20–30% of all congenital malformations. Within the CAKUT phenotypic spectrum, renal hypodysplasia (RHD) is particularly severe. This study aimed to evaluate the applicability of single-nucleotide polymorphism (SNP) array test in prenatal diagnosis of RHD for improving prenatal genetic counseling and to search for evidence of a possible causative role of copy-number variations (CNVs) in RHD.ResultsWe performed a systematic survey of CNV burden in 120 fetuses with RHD: 103 cases were isolated RHD and 17 were non-isolated RHD. Single-nucleotide polymorphism (SNP) array test was performed using the Affymetrix CytoScan HD platform. All annotated CNVs were validated by fluorescence in situ hybridization. We identified abnormal CNVs in 15 (12.5%) cases of RHD; of these CNVs, 11 were pathogenic and 4 were variants of uncertain significance. The detection rate of abnormal CNVs in non-isolated RHD was higher (29.4%, 5/17) than that in isolated RHD (9.7%, 10/103) (P = 0.060). Parents are more inclined to terminate the pregnancy if the fetuses have pathogenic results of the SNP-array test.ConclusionsThe variable phenotypes that abnormal CNVs may cause indicate the genetic counseling is needed for RHD cases.

Evaluation of IoT Capability in Detecting Kidney Malformations on Ultrasound Imaging System

Background: Remote radiology is used in the remote areas today to diagnose scanned ultrasound data due to the lack of trained radiologists. The availability of online radiography experts and the availability of portable ultrasound communication facilities are some of the issues in remote radiology for the use of ultrasound scanning in telehealth. Objectives: The purpose of the present study was to investigate the ability of IoT to detect computer abnormalities of kidneys on ultrasound imaging. Methods: The study was conducted systematically by searching the Scopus, Science Direct, PubMed, and Google Scholar search engine databases using the PRISMA flow diagram to select articles. The English language input and the time range of 2013 to 2018 were used for the search. There were about 123 articles, 42 of which were included in the study. Then, the qualitative evaluation of articles was done based on the 12-question CASP diagnostic test study checklist and finally, 15 articles related to the study were selected. Results: The results of studies showed that IoT was more acceptable and satisfactory than other imaging modalities and had a significant role in the diagnosis of kidney disease, in terms of both cost and time. Conclusion: The results of the study showed that in the absence of a radiologist in the therapeutic environment or the patient’s inability to visit the hospital or clinic, using IoT is the best way to solve the mentioned problems.