Screening for Renal and Urinary Tract Anomalies in Asymptomatic First Degree Relatives of Children with Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).

Congenital anomalies of the kidney and urinary tract (CAKUT) commonly cause chronic kidney disease in children. While most CAKUT cases are sporadic, observed familial clustering suggests that the pathogenesis is influenced by genetic factors. The purpose of the present study is to determine the frequency of the kidney and urinary tract anomalies in asymptomatic first-degree relatives of patients with CAKUT. A total of 218 index patients and their families followed at an academic hospital in Ankara, Turkey, were enrolled in the study. Family histories revealed at least one other member with a known kidney or urinary tract disease in 50% and CAKUT in 22.9% of the families. All asymptomatic first-degree relatives of 180 index patients were screened for kidney and urinary tract anomalies using ultrasound. New anomalies were diagnosed in 116 asymptomatic first-degree relatives (23%) in 87 families (48.3%). When family histories and ultrasound findings of 180 index patients were evaluated together, 129 first-degree relatives in 92 families (51.1%) had CAKUT. This study suggests that genetic mechanisms might be very important in the pathogenesis of apparently sporadic CAKUT. Identification of the underlying gene mutations will provide further insights into the knowledge of the kidney and urinary tract development and pathogenesis of CAKUT.

Non-syndromic congenital anomalies of kidney and urinary tract (CAKUT) are usually sporadic in nature but familial clustering of cases have been observed suggesting a genetic predisposition to this condition. We aimed to determine the frequency and pattern of renal anomalies in first-degree relatives of children with non-syndromic CAKUT. We screened all the first-degree relatives of children with CAKUT. A total of 149 first-degree relatives, belonging to 62 families were screened with ultrasonography. A renal anomaly was detected in 9 out of the 62 families. Two of these nine families had identical anomalies (child and a parent) indicating single-gene disorders with possible autosomal dominant inheritance, while the rest of families had a non-identical anomaly. The anomalies detected in the first-degree relatives were renal hypodysplasia (n = 2), multicystic dysplastic kidney (n = 3), pelviureteric junction obstruction (n = 2) and mild hydronephrosis (n = 2). The incidence of a sonographically detected anatomic renal anomaly in first-degree relatives of children with CAKUT was found to be 6.0%. Familial cystic kidney disease was found in two out of the 4 families with cystic kidney disease. Significant renal anomalies were identified in first-degree relatives of children with non-syndromic CAKUT and hence, attempts must be made to screen the family members of children with non-syndromic CAKUT.

Urinary Anomalies in 22q11.2 Deletion (DiGeorge syndrome): From Copy Number Variations to Single-Gene Determinants of Phenotype

The urinary tract malformations, today called CAKUT (Congenital Anomalies of the Kidney and Urinary Tract), include a range of morphological and/or functional abnormalities of the kidney and urinary tract diseases, apart from being the main cause of renal failure in children. The frequency of these birth defects is around 2% of pregnancies and many genetic syndromes may include CAKUT: about 500 of them have been described. The CAKUT concern localized alterations at different levels of the urinary system: hydronephrosis, vesicoureteral reflux, duplex collecting system, megaureter, kidney dysplasia. In the approach to the child with CAKUT it is important to identify a population at risk, distinguishing between CAKUT with and without clinical significance, applying a tailored approach to the individual patient, avoiding unnecessary investigations and treatments.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) often results in renal failure. Alhough the pathophysiology of CAKUT is still not completely understood, several maternal risk factors have been identified associated with children with CAKUT so far. Therefore, the aim of this study was to assess the proportion of risk factors of mothers gave birth to the infants with CAKUT. This cross-sectional study was conducted over a six-month period in the Departments of Pediatrics, Pediatric Nephrology, Neonatology and Pediatric Urology in Dhaka Shishu Hospital, Bangladesh from May 2018 to November 2018. A total of 200 infants aged ≤60 days and with a confirmed diagnosis of CAKUT were included in this study. Informed ascend was taken from the parents of the child. A semi-structured questionnaire was used for data collection, and statistical analysis was performed using SPSS version 21.0. This research was undertaken in conjunction with the ethical principles of Declaration of Helsinki. The mean age of the infants with CAKUT was 22.25±15.08 (SD) days with a male to female ratio of 1:1. The presenting anomalies were primary vesico-ureteral reflux (38.0%), pelvi-ureteric junction obstruction (20.0%), agenesis of the kidney (16.0%), posterior urethral valve (12.0%), dysplasia of the kidney (10.0%) and multicystic dysplastic kidney (3.5%). The most common pregestational risk factors were overweight (76.0%), diabetes mellitus (32.5%) and hypertension (29.5%) among the mothers. On the other hand, oligohydramnios (87.5%), gestational diabetes mellitus (67.0%) and gestational hypertension (45.5%) were the most frequently identified gestational risk factors. Pregestational overweight in women, maternal diabetes and oligohydramnios were most commonly identified risk factors among the mothers of CAKUT infant.

Diabetes-Induced Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): Nurture and Nature at Work?

‘Acro-renal syndrome’ refers to co-occurrence of congenital renal and limb anomalies. The term acro-renal syndrome was coined by Curran et al. in 1972 though Dieker and Opitz were the first to report this phenomenon in three male patients in 1969. The common limb defects include oligodactyly, ectrodactyly, syndactyly or brachydactyly anomalies of the carpal and tarsal bones and the common renal anomalies observed are unilateral renal agenesis (URA), bilateral renal hypoplasia, ureteric hypoplasia, hydroureteronephrosis and duplication abnormalities. The acro-renal syndrome as originally described is rare, reported only in ∼20 patients in the international literature. We report a 23-year-old male patient with renal anomalies in the form of absent right kidney, left-sided vesicoureteric reflux (VUR) and skeletal anomalies viz short radius, absent first metacarpal ray in left hand and left undescended testis, consistent with Dieker's type acro-renal syndrome. Apart from the classical acro-renal syndrome, several anomalies of acro-renal patterns and the abnormal gene loci involved are described in the literature. This article is a comprehensive review of the development of kidneys, types of acro-renal syndromes, congenital anomalies of the kidney and urinary tract (CAKUT), syndromes associated with combined limb and renal anomalies, and anomalies associated with URA.

1. Halima S. Janjua, MD* 2. Suet Kam Lam, MD, MPH, MS† 3. Vedant Gupta, DO‡ 4. Sangeeta Krishna, MD† 1. *Center for Pediatric Nephrology, 2. †Department of Pediatric Hospital Medicine, 3. ‡Department of Pediatrics, Cleveland Clinic Children’s, Cleveland, OH * Abbreviations: ARPKD: : autosomal recessive polycystic kidney disease CAKUT: : congenital anomalies of the kidney and urinary tract ESRD: : end-stage renal disease MCDK: : multicystic dysplastic kidney PUV: : posterior urethral valve RBUS: : renal and bladder ultrasonography UPJ: : ureteropelvic junction UTI: : urinary tract infection UVJ: : ureterovesical junction VCUG: : voiding cystourethrogram VUR: : vesicoureteral reflux Several congenital anomalies of the kidney and urinary tract are incidental findings. An understanding of when to suspect and how to diagnose, manage, and use timely and appropriate investigations and consults is necessary. After completing this article, readers should be able to: 1. Develop an awareness of various congenital anomalies of the renal system, including embryology, prevalence, and risk factors. 2. Describe the clinical presentation and management of renal and urinary tract anomalies, including which anomalies warrant further evaluation and the timing and utility of imaging modalities. 3. Develop an awareness of genetic syndromes affecting the kidneys and urinary tract with associated extrarenal manifestations. Congenital anomalies of the kidney and urinary tract (CAKUT) include a wide spectrum of anomalies, with a reported incidence of up to 2% of births. (1) CAKUT account for almost one-fourth of all birth defects. (2) These are major causes of kidney disease in children and account for more than 40% of end-stage renal disease (ESRD). CAKUT are usually detected by routine prenatal ultrasonography, although some cases are not diagnosed until adulthood. (3) When renal disease is suspected, a complete physical examination should be performed with particular focus on accurate blood pressure measurement; the abdomen for palpable kidneys and a distended bladder; the genitalia for the position of the meatus, penile abnormalities, and urine flow; and the back for signs of neural tube defects. Genetics play a major role in the etiology of CAKUT as family history is identified in 10% to 50% of affected children (Table). (4)(5) Similarly, 23% of asymptomatic first-degree relatives are found to be affected on screening. (4) Many environmental …

Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of kidney failure in childhood. Renal transplantation is the modality of treatment used for kidney failure that promotes improved quality of life for pediatric patients. It is believed that patients with CAKUT are more predisposed to developing graft reflux in the post-transplant period, but its influence on graft survival is poorly understood. A comparative analysis between patients with and without VUR in the graft was made to determine the impact of reflux on graft function and survival in pediatric CAKUT patients. A retrospective case-control study of patients undergoing first renal transplantation between April 2008 and October 2021 was done. The study included CAKUT individuals who underwent voiding cystourethrogram after transplantation. Patients were stratified into a group without reflux in the transplanted kidney (controls) and a group with reflux (cases). Six-year graft and patient survivals were calculated and compared using Kaplan-Meier curves and the log-rank test. A total of 257 CAKUT patients were studied. Of this group, 63 (24%) underwent voiding cystourethrogram after transplantation, and 48 (76%) had reflux in the transplanted kidney. Estimated six-year survival of the graft was 72% in the control group versus 96% in the case group (log-rank 0.889). The median follow-up time after transplantation in years was 7.6 in controls and 6.6 in cases (p = 0.383). Pediatric patients with CAKUT who presented reflux in transplanted kidneys had similar graft and patient survivals compared to patients without reflux.

Congenital anomalies of the kidney and urinary tract (CAKUT) are 1 of the major factors in young adults needing renal replacement therapy, but there is little extensive assessment of their incidence and risk factors. This study aimed to evaluate trends in the incidence of and risk factors for CAKUT among all births in Taiwan.This population-based case-control study design was conducted using the Taiwan national births registry, which contains detailed information about maternal health and characteristics of newborns, supplied by health professionals. Of 1,603,794 newborns registered between 2004 and 2014, 668 infants were reported to have CAKUT. Newborns without congenital anomalies were matched with CAKUT cases by birth year, month, and Apgar score in a ratio of 5:1. Odds ratio (OR) and 95% confidence interval (CI) for developing CAKUT were calculated using a conditional multivariate logistic regression model.The incidence of CAKUT was approximately 4.2 per 10,000 births. The adjusted ORs for CAKUT in newborns associated with maternal age of 20 to 29 (OR, 2.18; 95% CI, 1.11-4.28), or 30 to 39 (OR, 2.29; 95% CI, 1.17-4.51), maternal gestational diabetes (OR, 2.22, 95% CI, 1.06-4.67), maternal thalassemia/hemochromatosis (OR, 2.67; 95% CI, 1.35-5.27), polyhydramnios or oligohydramnios (OR, 9.16; 95% CI, 5.46-15.37), birth parity >1 (OR, 0.27; 95% CI, 0.15-0.50), having a gestational age <37 weeks (OR, 1.48; 95% CI, 1.23-1.78), and being a boy (OR, 1.83; 95% CI, 1.53-2.19). Infants of mother with gestational diabetes were more likely to have congenital anomalies, small gestational age (<37 weeks) and low birth weight.CAKUT are associated with several maternal health risk factors. As Taiwan has the highest prevalence and incidence rates of end-stage renal disease in the world, these findings strongly support the need to develop professional guidelines for prenatal counseling and management of women at risk of adverse birth outcomes, to prevent kidney disease progression and reduce complications.

This study aimed to explore the spatio-temporal expression patterns of congenital anomalies of kidney and urinary tract (CAKUT) candidate genes, Fibroblast Growth Factor Receptor 1 (FGFR1), Fibroblast Growth Factor Receptor 2 (FGFR2) and Receptor-Interacting Protein Kinase 5 (RIP5), in human fetal kidney development (CTRL) and kidneys affected with CAKUT. Human fetal kidneys from the 22nd to 41st developmental week (duplex, hypoplastic, dysplastic, and controls) were stained with antibodies and analyzed by epifluorescence microscopy and RT−qPCR. The effect of CAKUT candidate genes on kidney nephrogenesis and function is confirmed by statistically significant variations in the spatio-temporal expression patterns of the investigated markers. The nuclear localization of FGFR1, elevated expression score of FGFR1 mRNA, the increased area percentage of FGFR1-positive cells in the kidney cortex, and the overall decrease in the expression after the peak at the 27th developmental week in dysplastic kidneys (DYS), suggest an altered expression pattern and protein function in response to CAKUT pathophysiology. The RT−qPCR analysis revealed a significantly higher FGFR2 mRNA expression score in the CAKUT kidneys compared to the CTRL. This increase could be due to the repair mechanism involving the downstream mediator, Extracellular Signal-Regulated Kinase 1/2 (ERK1/2). The expression of RIP5 during normal human kidney development was reduced temporarily, due to urine production and increased later since it undertakes additional functions in the maturation of the postnatal kidney and homeostasis, while the expression dynamics in CAKUT-affected kidneys exhibited a decrease in the percentage of RIP5-positive cells during the investigated developmental period. Our findings highlight the importance of FGFR1, FGFR2, and RIP5 as markers in normal and pathological kidney development.

Background Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease (CKD) in children. Delayed diagnosis of CAKUT due to lack of universal screening (such as prenatal ultrasound screening or postnatal ultrasound screening in neonates with risk of CAKUT) has led to more cases of advanced CKD in children. CKD has high morbidity and mortality, and early detection is required to prevent the progression of CKD.&#x0D; Objective To determine the factors that predict the development of advanced CKD in children with CAKUT.&#x0D; Methods This retrospective cohort study included children with CAKUT at Dr. Sardjito Hospital, Yogyakarta, Indonesia from January 2016 to February 2021. Patients who were diagnosed with CAKUT were followed up to 5 years or until the onset of advanced CKD. Advanced CKD was defined as a decreased estimated glomerular filtration rate (eGFR) of less than 30mL/min/1.73m2 based on the revised Schwartz formula. CKD progression-free survival was determined with Kaplan-Meier and Cox regression analyses.&#x0D; Results Among 62 subjects with CAKUT, 7 (11.3%) subjects progressed to advanced CKD. The mean time of advanced CKD progression was 52.2 (95%CI 46.9 to 57.5) months. The overall incidence rate was 22 per 1,000 person-years. Based on Kaplan-Meier analysis, children with eGFR &lt;60 mL/min/1.73m2 at the time of diagnosis had more rapid progression to advanced CKD than patients with eGFR ?60 mL/min/1.73m2 [40.2 (95%CI 33.4 to 46.6) months vs. 58.2 95%CI 46.9 to 57.5) months; P=0.02, respectively].&#x0D; Conclusion Reduced eGFR at the time of diagnosis showed rapid progression to advanced CKD.

ObjectiveTo establish an effective screening model of congenital anomalies of the kidney and urinary tract (CAKUT) using ultrasound among neonates in Shanghai, China.DesignCross-sectional study.SettingA three-level screening model for CAKUT in...

Nearly 30% of childhood cases of chronic renal failure in Japan are attributed to congenital anomalies of the kidney and urinary tract (CAKUT), and the number is increasing. Urine screening at school facilitates early diagnosis and treatment of glomerulonephritis, but early screening for anomalies is currently not in practice. The authors evaluated the value of early abdominal ultrasonography screening in 1-month-old infants. The following characteristics of kidneys were assessed: presence versus absence, size, symmetry of size, position, separation of the central echo complex (CEC), abnormal echogenicity, and other abnormal findings. The bladder and ureter were checked for abnormalities in bladder shape and wall, as well as retrovesical ureteral dilation. Criteria for abnormalities included kidney length of <or=35 mm, or >or=60 mm; a difference in length of left and right kidneys of 10 mm or more; and CEC separation of Society for Fetal Urology (SFU) grade 2 or higher. Beginning in April 1994 and continuing until September 2001, screening of 5700 1-month-old infants yielded 198 positive cases (3.5%) of CAKUT. Most frequent was abnormal CEC separation (approximately 60% of all abnormalities), followed by abnormal renal size or size asymmetry (30%). Further investigation yielded a specific diagnosis in 32 cases (0.6%) of all subjects. Most prevalent was obstructive uropathy (15 cases); 8 children underwent surgery. Small kidneys and vesicoureteral reflux were next in frequency. Ultrasonograpy was effective for early detection of renal and urinary tract anomalies. Ultrasound screening in early infancy may permit early treatment, that can prevent renal dysfunction.

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading causes of chronic kidney disease (CKD) in childhood. Determining the clinical course, outcome, and prognostic factors of this heterogeneous group of diseases is important to provide appropriate management and follow-up. Therefore, we aimed to identify the risk factors of CKD in CAKUT and the differences in clinical courses between subtypes of CAKUT. Methods: a retrospective cross-sectional study was done in 134 patient records diagnosed with congenital kidney and urinary tract anomalies. They were categorized with subtypes of CAKUT and a chi-square test and logistic regression analysis were done to determine risk factors for CKD and the result is presented in tables. Results: Among the 134 patients, males were 107 (79.9%) and the commonest subtypes of CAKUT were posterior urethral valve in 42 (31.3%), ureteropelvic junction obstruction in 28 (20.9%), multicystic dysplastic kidney in 24 (17.9%). The median age of the study population at the time of diagnosis was 2.5 yrs. Among available 50 prenatal ultrasounds, the most frequent diagnoses were hydronephrosis in 38 patients (28.4%) and MCDK in 9 patients (6.7%). A total of 21(15.7%) patients had CKD and 6 of them (4.5%) progressed to end-stage kidney disease (ESRD). The multivariate logistic regression analysis identified proteinuria on follow-up as an independent risk factor for CKD. (p=0.004) Conclusion: Posterior urethral valve is the commonest congenital anomaly of the kidney and urinary tract and proteinuria is an independent risk factor for CKD.