Trends and socioeconomic inequality of the burden of congenital abnormalities of the kidney and urinary tract among children and adolescents.

BACKGROUND: Although congenital abnormalities of the kidney and urinary tract (CAKUT) is the leading cause of childhood onset chronic kidney disease (CKD) and kidney failure, comprehensive information on the disease burden among children and adolescents globally is lacking. We aim to report the trends and socioeconomic inequality of CAKUT burden for people aged 0-24 years from 1990 to 2019·. METHODS: We reported the prevalence, mortality and disability-adjusted life-years (DALYs) for CAKUT based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, quantified the association of disease burden and socio-demographic index (SDI), calculated the slope index of inequality (SII) the relative index of inequality (RII) and concentration index. RESULTS: In 2019, the global prevalence, mortality, and DALYs of CAKUT among individuals aged 0-24 years were 167.11 (95%Confident Interval 166.97, 167.25), 0.30 (0.29, 0.30), and 32.22 (32.16, 32.29) per 100 000 population. The greatest prevalence, mortality and DALYs were recorded in the 0-4 year age group. The greatest mortality and DALYs were recorded in low SDI countries and territories. During 1990 to 2019, the prevalence, mortality and DALYs decreased globally, while in low and low-middle countries and territories the reduction was much less slower. India, Nigeria and Pakistan had the highest DALYs. Saudi Arabia and China exhibited a markedly decrease of CAKUT burden. Globally for every 0.1 increase in SDI, there was a 20.53% reduction in mortality, a 16.31% decrease in DALYs, but a 0.38% rise in prevalence. CONCLUSIONS: Inequality for disease burden of varying SDI was increasing globally. Thus, specific preventive and health service measures are needed to reduce the global burden from CAKUT.

Targeted next-generation sequencing in a large series of fetuses with severe renal diseases.

We report the screening of a large panel of genes in a series of 100 fetuses (98 families) affected with severe renal defects. Causative variants were identified in 22% of cases, greatly improving genetic counseling. The percentage of variants explaining the phenotype was different according to the type of phenotype. The highest diagnostic yield was found in cases affected with the ciliopathy-like phenotype (11/15 families and, in addition, a single heterozygous or a homozygous Class 3 variant in PKHD1 in three unrelated cases with autosomal recessive polycystic kidney disease). The lowest diagnostic yield was observed in cases with congenital anomalies of the kidney and urinary tract (9/78 families and, in addition, Class 3 variants in GREB1L in three unrelated cases with bilateral renal agenesis). Inheritance was autosomal recessive in nine genes (PKHD1, NPHP3, CEP290, TMEM67, DNAJB11, FRAS1, ACE, AGT, and AGTR1), and autosomal dominant in six genes (PKD1, PKD2, PAX2, EYA1, BICC1, and MYOCD). Finally, we developed an original approach of next-generation sequencing targeted RNA sequencing using the custom capture panel used for the sequencing of DNA, to validate one MYOCD heterozygous splicing variant identified in two male siblings with megabladder and inherited from their healthy mother.

A unique case of extrarenal calyces and associated vascular variations in an adult female cadaver.

The following urogenital and vascular anomalies were observed in the left kidney of an 81-year-old female cadaver during routine dissection: three extrarenal calyces; an accessory renal artery originating directly from the abdominal aorta; and a circumaortic renal vein. The typical renal anatomical structures were identified, from anterior to posterior, as the renal vein, renal artery, and ureter appearing near the hilum of the left kidney. After closer examination, three extrarenal calyces were observed exiting from the hilum of the left kidney to form the pelvis, then narrowed and became the ureter which descended 21.5 cm to empty into the bladder. The accessory renal artery originated from the lateral aspect of the abdominal aorta 7.3 cm below the aortic origin of the left renal artery. A corresponding accessary renal vein, identified as a circumaortic vein, left the hilum 4.5 cm below the left renal vein and travelled posterior to the abdominal aorta to drain into the inferior vena cava. Extrarenal calyces are rare among urogenital tract variations. They can be associated with embryological abnormalities such as renal ectopia, horseshoe kidney or malrotation as well as clinical manifestations such as pelviureteric junction obstruction and hydronephrosis. Compression of the accessory renal artery can cause decreased blood flow to the inferior pole of the left kidney, thereby causing fibrosis, atrophy, or renal failure. The retro-aortic path of the circumaortic renal vein has been associated with posterior nutcracker phenomenon, haematuria, left renal vein thrombus formation, and renal vein hypertension. This unique combination of a collecting system anomaly and extrarenal vessel variations could have significant implications in abdominal surgery.

Pulmonary Manifestations of Renal Disorders in Children.

The causes of kidney disease in pediatric patients are evenly divided between congenital abnormalities of the kidney and urinary tract and acquired disorders. Nearly 10% to 15% of adults in the United States have chronic kidney disease (CKD); there are no comparable data in children. Regardless of patient age, CKD is a systemic problem that affects every organ system, including the lung. We review the tests used to diagnose and evaluate kidney disease and the main clinical syndromes that are likely to be encountered to aid the pulmonology consultant who is asked to evaluate patients with kidney disease.

Computer-Aided Diagnosis of Congenital Abnormalities of the Kidney and Urinary Tract in Children Using a Multi-Instance Deep Learning Method Based on Ultrasound Imaging Data.

Ultrasound images are widely used for diagnosis of congenital abnormalities of the kidney and urinary tract (CAKUT). Since a typical clinical ultrasound image captures 2D information of a specific view plan of the kidney and images of the same kidney on different planes have varied appearances, it is challenging to develop a computer aided diagnosis tool robust to ultrasound images in different views. To overcome this problem, we develop a multi-instance deep learning method for distinguishing children with CAKUT from controls based on their clinical ultrasound images, aiming to automatic diagnose the CAKUT in children based on ultrasound imaging data. Particularly, a multi-instance deep learning method was developed to build a robust pattern classifier to distinguish children with CAKUT from controls based on their ultrasound images in sagittal and transverse views obtained during routine clinical care. The classifier was built on imaging features derived using transfer learning from a pre-trained deep learning model with a mean pooling operator for fusing instance-level classification results. Experimental results have demonstrated that the multi-instance deep learning classifier performed better than classifiers built on either individual sagittal slices or individual transverse slices.

Computer-aided diagnosis of congenital abnormalities of the kidney and urinary tract in children based on ultrasound imaging data by integrating texture image features and deep transfer learning image features.

INTRODUCTION: Anatomic characteristics of kidneys derived from ultrasound images are potential biomarkers of children with congenital abnormalities of the kidney and urinary tract (CAKUT), but current methods are limited by the lack of automated processes that accurately classify diseased and normal kidneys. OBJECTIVE: The objective of the study was to evaluate the diagnostic performance of deep transfer learning techniques to classify kidneys of normal children and those with CAKUT. STUDY DESIGN: A transfer learning method was developed to extract features of kidneys from ultrasound images obtained during routine clinical care of 50 children with CAKUT and 50 controls. To classify diseased and normal kidneys, support vector machine classifiers were built on the extracted features using (1) transfer learning imaging features from a pretrained deep learning model, (2) conventional imaging features, and (3) their combination. These classifiers were compared, and their diagnosis performance was measured using area under the receiver operating characteristic curve (AUC), accuracy, specificity, and sensitivity. RESULTS: The AUC for classifiers built on the combination features were 0.92, 0.88, and 0.92 for discriminating the left, right, and bilateral abnormal kidney scans from controls with classification rates of 84%, 81%, and 87%; specificity of 84%, 74%, and 88%; and sensitivity of 85%, 88%, and 86%, respectively. These classifiers performed better than classifiers built on either the transfer learning features or the conventional features alone (p < 0.001). DISCUSSION: The present study validated transfer learning techniques for imaging feature extraction of ultrasound images to build classifiers for distinguishing children with CAKUT from controls. The experiments have demonstrated that the classifiers built on the transfer learning features and conventional image features could distinguish abnormal kidney images from controls with AUCs greater than 0.88, indicating that classification of ultrasound kidney scans has a great potential to aid kidney disease diagnosis. A limitation of the present study is the moderate number of patients that contributed data to the transfer learning approach. CONCLUSIONS: The combination of transfer learning and conventional imaging features yielded the best classification performance for distinguishing children with CAKUT from controls based on ultrasound images of kidneys.

Association between cord blood cystatin C levels and early mortality of neonates with congenital abnormalities of the kidney and urinary tract: a single-center, retrospective cohort study.

BACKGROUND: Some fetuses with congenital abnormalities of the kidney and urinary tract (CAKUT) have severe renal dysfunction during the prenatal period that can result in oligohydramnios, pulmonary hypoplasia, and death following birth. We hypothesized that cord blood cystatin C (CysC) levels are elevated in neonates who have life-threatening pulmonary hypoplasia and oligohydramnios due to severe renal dysfunction. In this study we compared cord blood CysC levels between a non-survivor group with CAKUT and a survivor group. METHODS: This was a single-center, retrospective cohort study conducted between January 2007 and December 2015. Eighty-seven neonates who were prenatally diagnosed with CAKUT were included in the study. Cord blood CysC and creatinine levels were compared between the survivor and non-survivor groups at discharge from hospital. RESULTS: Of the 87 neonates enrolled in the study, 67 survived and 21 died before discharge. Median cord blood CysC levels were higher in the non-survivor group than in the survivor group (4.28 vs. 1.96 mg/L, respectively; p < 0.001). Cord blood creatinine levels were not significantly different between the two groups. In patients with oligohydramnios (n = 28), cord blood CysC levels were significantly higher in the non-survivor group than in the survivor group (4.28 vs. 2.23 mg/L, respectively; p = 0.002). CONCLUSIONS: In this study population, cord blood CysC levels were significantly higher in the non-survivor group with CAKUT than in the survivor group. These results suggest that cord blood CysC levels may be a good marker of the severity of renal dysfunction at birth.

Genetics of Congenital Anomalies of the Kidney and Urinary Tract: The Current State of Play.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most frequent form of malformation at birth and represent the cause of 40-50% of pediatric and 7% of adult end-stage renal disease worldwide. The pathogenesis of CAKUT is based on the disturbance of normal nephrogenesis, secondary to environmental and genetic causes. Often CAKUT is the first clinical manifestation of a complex systemic disease, so an early molecular diagnosis can help the physician identify other subtle clinical manifestations, significantly affecting the management and prognosis of patients. The number of sporadic CAKUT cases explained by highly penetrant mutations in a single gene may have been overestimated over the years and a genetic diagnosis is missed in most cases, hence the importance of identifying new genetic approaches which can help unraveling the vast majority of unexplained CAKUT cases. The aim of our review is to clarify the current state of play and the future perspectives of the genetic bases of CAKUT.

Renal development in the fetus and premature infant.

Congenital abnormalities of the kidney and urinary tract (CAKUT) are one of the leading congenital defects to be identified on prenatal ultrasound. CAKUT represent a broad spectrum of abnormalities, from transient hydronephrosis to severe bilateral renal agenesis. CAKUT are a major contributor to chronic and end stage kidney disease (CKD/ESKD) in children. Prenatal imaging is useful to identify CAKUT, but will not detect all defects. Both genetic abnormalities and the fetal environment contribute to CAKUT. Monogenic gene mutations identified in human CAKUT have advanced our understanding of molecular mechanisms of renal development. Low nephron number and solitary kidneys are associated with increased risk of adult onset CKD and ESKD. Premature and low birth weight infants represent a high risk population for low nephron number. Additional research is needed to identify biomarkers and appropriate follow-up of premature and low birth weight infants into adulthood.

Multi-modality imaging review of congenital abnormalities of kidney and upper urinary tract.

Congenital abnormalities of the kidney and urinary tract (CAKUT) include a wide range of abnormalities ranging from asymptomatic ectopic kidneys to life threatening renal agenesis (bilateral). Many of them are detected in the antenatal or immediate postnatal with a significant proportion identified in the adult population with varying degree of severity. CAKUT can be classified on embryological basis in to abnormalities in the renal parenchymal development, aberrant embryonic migration and abnormalities of the collecting system. Renal parenchymal abnormalities include multi cystic dysplastic kidneys, renal hypoplasia, number (agenesis or supernumerary), shape and cystic renal diseases. Aberrant embryonic migration encompasses abnormal location and fusion anomalies. Collecting system abnormalities include duplex kidneys and Pelvi ureteric junction obstruction. Ultrasonography (US) is typically the first imaging performed as it is easily available, non-invasive and radiation free used both antenatally and postnatally. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to confirm the ultrasound detected abnormality, detection of complex malformations, demonstration of collecting system and vascular anatomy and more importantly for early detection of complications like renal calculi, infection and malignancies. As CAKUT are one of the leading causes of end stage renal disease, it is important for the radiologists to be familiar with the varying imaging appearances of CAKUT on US, CT and MRI, thereby helping in prompt diagnosis and optimal management.

Genomic and epigenomic analyses of monozygotic twins discordant for congenital renal agenesis.

Monozygotic twins have been widely studied to distinguish genetic and environmental factors in the pathogenesis of human diseases. For renal agenesis, the one-sided absence of renal tissue, the relative contributions of genetic and environmental factors to its pathogenesis are still unclear. In this study of a pair of monozygotic twins discordant for congenital renal agenesis, the genomic profile was analyzed from a set of blood samples using high-throughput exome-capture sequencing to detect single-nucleotide polymorphisms (SNPs), copy number variations (CNVs), and insertions and deletions (indels). Also, an epigenomic analysis used reduced-representation bisulfite sequencing to detect differentially methylated regions (DMRs). No discordant SNPs, CNVs, or indels were confirmed, but 514 DMRs were detected. KEGG analysis indicated the DMRs localized to 10 signaling pathways and 25 genes, including the mitogen-activated protein kinase pathway and 6 genes (FGF18, FGF12, PDGFRA, MAPK11, AMH, CTBP1) involved in organ development. Although methylation results from our adult patient and her sister may not represent the pattern that was present during kidney development, we could at least confirm a lack of obvious differences at the genome level, which suggests that nongenetic factors may be involved in the pathogenesis of renal agenesis.