Congenital Anomalies Of Kidneys Research Articles

Prospective observational study on clinical profile of congenital anomalies of kidney and urinary tract (CAKUT) in children in central India: A study protocol

Background Congenital anomalies of the kidney and urinary tract (CAKUT) are a group of structural abnormalities affecting these vital organs, frequently leading to chronic kidney disease in children. This study aims to comprehensively understand the clinical profile of CAKUT in children in Central India, an area with unique socio-demographic characteristics and limited prior research on this topic. Methods A prospective observational study will be conducted over three years in the pediatric department of AVBRH, a tertiary healthcare center in Central India. Data were collected through interviews with parents or guardians of children up to 18 admitted to the hospital. Clinical symptoms, prenatal history, physical examinations, and diagnostic investigations were meticulously documented. Expected outcome The study is expected to reveal the prevalence and clinical profile of CAKUT in Central Indian children. Anticipated outcomes include insights into anomalies, clinical symptoms, and potential correlations with factors like prenatal care and consanguineous marriages. Diagnostic investigations will help assess the severity of renal impairment. The results may also uncover regional variations and have implications for public health initiatives aimed at early intervention and improved patient care. However, these are preliminary expectations that are subject to confirmation through the completion of the study.

Neonatal jaundice is associated with increased risks of congenital anomalies of the kidney and urinary tract and concomitant urinary tract infection

The link between neonatal jaundice and urinary tract infection (UTI) remains debated, with congenital kidney and urinary tract anomalies (CAKUT) potentially playing a role. This population-based study aimed to analyze the correlations between neonatal jaundice, CAKUT, and concomitant UTI. The study cohort consisted of 2,078,122 live births from 2004 to 2014. We linked several population-based datasets in Taiwan to identify infants with unexplained neonatal jaundice and their mothers. The primary outcome was the rate of CAKUT occurring within 3 years after delivery, and the presence of concomitant UTI during neonatal jaundice hospitalization. Infants with neonatal jaundice had a significantly higher risk of CAKUT (adjusted odds ratio [aOR] 1.24, 95% confidence interval [CI] 1.11–1.39) during early childhood. Among the subtypes of CAKUT, obstructive uropathy, vesicoureteral reflux and other CAKUT were associated with an increased risk of neonatal jaundice. Infants who underwent intensive phototherapy, had a late diagnosis (> 14 days of postnatal age) or underwent a prolonged duration of phototherapy (> 3 days) exhibited a higher risk of concomitant UTI compared to other infants with jaundice. Our findings indicate a notable association between neonatal jaundice and increased risks of UTIs in the context of CAKUT. This study underscore the importance of vigilant monitoring and timely interventions for neonates presenting with jaundice, while acknowledging the complexity and variability in the progression of CAKUT and its potential connection to UTIs.

Congenital anomalies of kidney and urinary tract (CAKUT) and associated extra-renal anomalies in fetal autopsies.

According to studies, 1% of all pregnancies have an abnormality, with 20-30% of those affecting the genitourinary system. Congenital abnormalities of the kidney and urinary tract (CAKUT) is one of the primary causes of perinatal and neonatal mortality in children. Many extra-renal congenital illnesses accompany these defects, affecting the patient's prognosis. This study aims to determine the subtypes, frequency, and extra-renal defects associated with congenital anomalies of the urinary system, which is the major cause of mortality in fetal and infant autopsies throughout the perinatal and neonatal eras. We believe that our study will contribute to the literature because few autopsy investigations can give this data. The study included 110 fetal autopsies between January 1997 and May 2019. 10% were newborns under the age of one year, and 90% were fetus autopsies. Males accounted for 67.3% of the cases, while females accounted for 35 (31.8%) (the gender of one case could not be determined). Renal dysplasia was the most frequent CAKUT, with a rate of 22.73%, followed by renal agenesis, with a rate of 20.0%. Eighty-four cases (76.3%) showed disease in at least one other organ system. Musculoskeletal system (MSS) abnormalities were the most common associated system anomaly, with one or more MSS anomalies (34.55%) detected in 38 cases. Finally, we want to underline that CAKUT and its associated anomalies are not uncommon. Prenatal imaging, genetic investigation, and/or postmortem examination should all be used to screen for CAKUT. This information is helpful for the mother's future pregnancy management and parental genetic counseling.

Antenatal hydronephrosis – surrogate marker of congenital kidney and urinary tract anomalies in children Suggested citation for this article: Picioreanu I, Picioreanu DM. Antenatal hydronephrosis – surrogate marker of congenital kidney and urinary tract anomalies in children. Medic.ro. 2024;157(1):12-20.

Antenatal hydronephrosis – surrogate marker of congenital kidney and urinary tract anomalies in children Suggested citation for this article: Picioreanu I, Picioreanu DM. Antenatal hydronephrosis – surrogate marker of congenital kidney and urinary tract anomalies in children. Medic.ro. 2024;157(1):12-20.

Acute kidney injury in birth asphyxiated patients: A cross sectional study at Bahawal Victoria Hospital.

The presence of perinatal asphyxia and its severity appear to correlate with increasing incidence of Acute kidney injury (AKI). The objective of this study is to determine the frequency of AKI and its outcome in birth asphyxia. This cross-sectional study was carried out in the Department of Pediatric Medicine from March 2019 to September 2019. A total of 111 newborns with birth asphyxia of gestational age 37-41 weeks were included. Neonates born to mothers having hypertension and diabetes mellitus, patients with congenital kidney anomalies like polycystic kidney disease and renal agenesis, and mothers taking nephrotoxic drugs or any other known cause of AKI like hypovolemic shock were excluded. Urine output (UOP) and final outcome of the patient were also noted. AKI was noted. The mean gestational age was 38.29 ± 1.07 weeks. The mean weight of neonates was 3.08 ± 0.31 kg. The frequency of AKI in birth asphyxia was 20 (18.02%) neonates. Complete recovery in AKI patients was seen in 07 (35.0%) and death in 13 (65.0%) patients. This study has shown that the frequency of AKI in birth asphyxia was found in 18.02% neonates with complete recovery seen in 35.0% and death in 65.0% patients.

Hospitalizations after Renal Transplantation in Children: Risk Factors, Causes, and Outcomes

Introduction: The aims of this study were to evaluate the frequency and causes of hospitalizations in the posttransplant period of children, investigate the risk factors, and evaluate the relationship between hospitalizations and renal prognosis in the long term. Methods: We retrospectively reviewed the files of pediatric renal transplant patients, followed at least 6 months after kidney transplantation, in our center. Clinical information including age at transplantation, gender, primary disease, donor type, immuno-suppressive medication, hospitalization dates, and indications (infections and non-infectious) during follow-up period and graft outcomes was recorded. Results: A total of 74 children (46 males) were followed up for a median of 54 months. Among them, 69 patients (93.2%) were hospitalized 446 times. The most common cause of hospitalizations was infections (314 times, 70%). Urinary tract infections were the most important cause followed by upper respiratory tract infections. Forty (54%) patients were hospitalized 132 times (29.5%) for non-infectious reasons. The most common non-infectious reason was nonspecific graft dysfunction (19 patients, 30 times), followed by rejection (17 patients, 27 times). Younger age, use of induction therapy, and having congenital anomalies of kidney and urinary tract (CAKUT) were found to be risk factors for increased hospitalization rates (p < 0.05). The number of hospitalizations was found to be negatively affecting the final glomerular filtration rate of transplant recipients (p: 0.04, r: –0.023). Conclusion: Patients with CAKUT, who received induction therapy, and small children were hospitalized more frequently after transplantation. Strategies to prevent hospitalizations will achieve a better graft prognosis.

Ukraine: Chronic Kidney Disease in children and adolescents: retrospective and priorities

The present study aimed to assess the prevalence and structure of chronic kidney disease (CKD) in children and adolescents to determine the priorities for the development of pediatric nephrology in Ukraine.&#x0D; Methods. Individuals who were born in Ukraine after 1994 and had CKD diagnosed before the age of 18 were investigated. The number of CKD cases was estimated per 100,000 newborns depending on the year of birth, divided into time intervals: 1995-2004 and 2005-2022 years of birth. Both groups were stratified with the generalization of the etiological component. The patients on Kidney Replacement Therapy (KRT) were separated into special clinical group, and the etiological and age spectrum analysis of KRT initiation was performed depends of the year of birth. In addition, cross-sectional analysis of the etiological structure of KRT incidence and prevalence in years 2019 and 2021 was conducted.&#x0D; Results. The prevalence of CKD in children and adolescents in Ukraine increased over a long period up to year 2022 (average cases per 100,000 births: 43.5 in years 1995-2004, 37.0 in years 2005-2022:) with an amplification of early stages (CKD1-4: year 2010 - 81.4%, year 2022 - 92.0%) and KRT decrease, respectively (average cases per 100,000 births: 6.5 and 3.3 in the analyzed time intervals). The individuals with primary urological pathology made up a third or more among CKD patients (depending on the year of birth). The etiological and age spectrum differences of KRT were determined in the analyzed time intervals. Depending on the underlying cause of CKD, the age of KRT initiation in born before year 2005 varied from 9 to 16 years, in the following period - from 1 to 9 years.&#x0D; The differences from the ESPN Registry were identified in cross-sectional etiological spectrum of CKD with KRT initiation in year 2019 (age up to 15 years old): the higher proportion of patients after Acute Kidney Injury/AKI (16.7%) or with glomerulonephritis/GN (30.0%), and the smaller one of congenital anomalies of kidney and urinary tract/CAKUT (26.6%). The distribution of KRT causes in Ukraine under the age of 18 did not change in years 2019 and 2021 (including polycystic kidney disease/PKD 12.1-11.2%, GN 15.0-16.5%, AKI 12.1-13.1%, CAKUT 32.4-31.0%, respectively), but only for CAKUT and PKD was approximated to ISPN Global Registry data.&#x0D; Conclusions. The revealed qualitative changes in the etiological and age structure of morbidity over a long period in Ukraine indicate the CKD pathomorphosis and require updating the clinical managment of patients depends of the economic and organizational potential of the country, the challenges of martial law and the difficulties of the next recovery period.

Integrated analysis of copy number variation-associated lncRNAs identifies candidates contributing to the etiologies of congenital kidney anomalies

Congenital anomalies of the kidney and urinary tract (CAKUT) are disorders resulting from defects in the development of the kidneys and their outflow tract. Copy number variations (CNVs) have been identified as important genetic variations leading to CAKUT, whereas most CAKUT-associated CNVs cannot be attributed to a specific pathogenic gene. Here we construct coexpression networks involving long noncoding RNAs (lncRNAs) within these CNVs (CNV-lncRNAs) using human kidney developmental transcriptomic data. The results show that CNV-lncRNAs encompassed in recurrent CAKUT associated CNVs have highly correlated expression with CAKUT genes in the developing kidneys. The regulatory effects of two hub CNV-lncRNAs (HSALNG0134318 in 22q11.2 and HSALNG0115943 in 17q12) in the module most significantly enriched in known CAKUT genes (CAKUT_sig1, P = 1.150 × 10−6) are validated experimentally. Our results indicate that the reduction of CNV-lncRNAs can downregulate CAKUT genes as predicted by our computational analyses. Furthermore, knockdown of HSALNG0134318 would downregulate HSALNG0115943 and affect kidney development related pathways. The results also indicate that the CAKUT_sig1 module has function significance involving multi-organ development. Overall, our findings suggest that CNV-lncRNAs play roles in regulating CAKUT genes, and the etiologies of CAKUT-associated CNVs should take account of effects on the noncoding genome.

Incremental hemodialysis in pediatric patients.

Incremental hemodialysis follows the concept of adjusting dialysis dose according to residual kidney function. Data on incremental hemodialysis in pediatric patients is lacking. We conducted a retrospective analysis of children initiating hemodialysis between January 2015 and July 2020 in a single tertiary center, comparing the characteristics and outcomes of those who commenced with incremental hemodialysis vs with conventional thrice-weekly regimen. Data onforty patients, 15 (37.5%) on incremental hemodialysis and 25 (63%) on thrice-weekly hemodialysis were analyzed. No differences in age, estimated glomerular filtration rate and metabolic parameters were noted between groups at baseline, but there were more males (73 vs 40%, p = 0.04), more patients with congenital anomalies of kidney and urinary tract (60 vs 20%, p = 0.01), higher urine output (2.5 ± 1 vs 1 ± 0.8ml/kg/h, p < 0.001), lower use of antihypertensive medications (20 vs 72%, p = 0.002) and lower prevalence of left ventricular hypertrophy (6.7 vs 32%, p = 0.003) in the incremental hemodialysis group vs thrice-weekly hemodialysis. During follow up, 5 (33%) incremental hemodialysis patients were transplanted, 1 (7%) remained on incremental hemodialysis at 24months, and 9 (60%) transitioned to thrice-weekly hemodialysis at a median (IQR) time of 8.7 (4.2, 11.8) months. At last follow up, fewer patients who initiated incremental hemodialysis had left ventricular hypertrophy (0 vs 32%, p = 0.016) and urine output < 100ml/24h (20 vs 60%, p = 0.02) compared to thrice-weekly hemodialysis, with no significant differences in metabolic or growth parameters. Incremental hemodialysis is a viable option for initiating dialysis in selected pediatric patients, that may help improve patients' quality of life and reduce dialysis burden without compromising clinical outcome.

Prevalence of Enterococcal Urinary Tract Infections With Positive Nitrites in Urinalysis in Pediatric Patients With High-Risk for Enterococcal Infections.

Enterococcus is a relatively uncommon pathogen that causes urinary tract infections (UTIs) in healthy children. Most enterococcal infections occur in patients with risk factors such as anatomical or functional urinary tract anomalies, also known as CAKUT (congenital anomalies of kidney and urinary tract). Children who are suspected of having UTIs and who have certain risk factors are often treated specifically for enterococcal infection as part of their empiric regimen. Our primary objective was to determine the prevalence of enterococcal UTIs among high-risk children, and specifically among those with positive nitrite tests, with the goal of avoiding treatment with specific anti-enterococcal agents. This retrospective study included all the episodes of UTI treated at a tertiary pediatric center during 2010 to 2018. The data collected from medical records included nephrological and urological risk factors, nitrite status, and isolated pathogens. Of 931 episodes of UTI, 467 (50%) were considered high-risk. In all, 24 of the latter had Enterococcus as a single pathogen; 23 (96%) of these occurred in patients with negative nitrites in the first urine dipstick taken. The sole patient with high-risk factors, a positive nitrite test and coexisting enterococcal UTI had a history of previous enterococcal UTIs. In pediatric patients with nephrological and urological risk factors, who have positive nitrites in urinalysis, the risk for enterococcal UTI appears substantially low. Therefore, in this context, specific anti-enterococcal empirical antibiotic therapy may be unnecessary.

#4923 ARTERIOVENOUS FISTULAS AS HEMODIALYSIS ACCESS IN A PEDIATRIC POPULATION – IS YOUNGER AGE A REASON TO MAINTAIN CENTRAL VENOUS CATHETER?

Abstract Background and Aims In the pediatric population, transplantation remains the first-line therapy in patients with end-stage renal disease (ESRD). However, it is not always possible, increasing the need for other kidney replacement therapy (KRT) modalities, and hemodialysis (HD) has been growing as a modality choice in recent years. To provide quality HD treatment, efficient vascular access is mandatory, and the arteriovenous fistula (AVF) is advocated as the best long-term access option. However, its creation is technically challenging, and its development and maintenance are some of the most difficult elements in the pediatric population. In this study, we describe our experience in the utilization of AVFs in children and adolescents on HD. Method We conducted a retrospective study including all the AVFs performed in our center on underage patients between January 2006 and December 2022. We reviewed the medical records, collected data on demographic variables, AVF characteristics, blood test results, and clinical outcomes. Statistical analysis was performed using SPSS software. Results Forty-three AVFs were performed in 32 pediatric patients. The median age at first AVF construction was 13.5 years (min 4.8; max 17.9). The most frequent etiology of ESRD was congenital anomalies of kidney and urinary tract (n = 20, 62.5%) and most patients (n = 24, 75.0%) were already receiving KRT. Median follow-up time was 16.4 months (min 1; max 98.4) and, at the end of the follow-up period, most patients (n = 22, 68.8%) were transplanted. The mortality rate was 6.3% (n = 2). In what concerns to the location of the AVF, radiocephalic was the first choice in 46.9% of the cases (n = 15), accounting for 34.9% of the total AVFs. Brachiocephalic location was used in 34.4% (n = 11) of first fistulas and 6 subsequent accesses, accounting for 39.5% of the total AVFs. The brachiobasilic location was chosen in 18.8% (n = 6) of the first AVFs and 25.6% of the total AVFs. Primary AVF failure occurred in 26.6% (n = 11) cases and, in 4 of these (36.4%), it was possible to successfully use the same location for a second AVF. We observed no statistical association between primary AVF failure dysfunction and gender, age at the construction of the first fistula, AVF location, or dialysis vintage. Platelet-lymphocyte (PLR) and neutrophil-lymphocyte (NLR) ratios also did not differ between groups. Primary and secondary patency rates at one year were, respectively, 62.5% and 93.8%. With respect to total AVF complications, we observed: thrombosis (27.9%), stenosis (18.6%), distal ischemia induced by vascular access (4.7%), and high flow/aneurismatic dilations (18.6%). The presence of complications was statistically related to age (p = 0.046), with more events in older patients at the time of AVF construction. There was no statistical difference between complications’ occurrence and AVF type, sex, gender, PLR, and NLR. Conclusion The utilization of AVF for HD has been growingly recognized as a safe and efficient alternative for the performance of KRT in pediatric patients. Although larger studies are needed, we demonstrate positive results in its usage in a pediatric population, with high primary and secondary patency rates. These outcomes were independent of the AVF location. We also advocate AVF usage in younger patients, as complications were associated with older age. PLR and NLR, which are emerging biomarkers for systemic inflammation, were not associated with AVF dysfunction, aligning with the results of other studies in pediatrics.

#4285 CAUSES OF PEDIATRIC END STAGE KIDNEY DISEASE IN SUDAN

Abstract Background and Aims Sudan is a large Sub-Saharan country with a population of about 48 million people, 41% of them under the age of 15 years and a median age of 18.9 years. To data, no data have been reported on the etiology of end stage kidney disease (ESKD) in children and young adults of less than 18 years of age. Method We conducted a chart review of all ESKD patients below the age of 18 years treated in a tertiary referral center, the Soba University Hospital (SUH) in Khartoum, the capital of Sudan. The research was approved by the SUH ethical committee. We report descriptive statics, including age, sex, ESKD causes, and kidney biopsy frequency. Results We included 885 patients in this analysis, their mean age (SD) was 12 (3.0) years and 57.7% were males. Glomerulonephritis, mostly post-streptococcal glomerulonephritis, was the leading cause of ESKD (36.8%), followed by unknown etiologies (25.3%) and congenital anomalies of kidney and urinary tract (CAKUT; 14.9%). In most patients with glomerulonephritis the diagnosis was based on kidney histology (96.6%). ESKD was attributed to HUS in about 7% of patients. As expected, SLE was more prevalent in females (3:1 ratio) and hereditary nephritis in males (3:1). Conclusion Glomerulonephritis and CAKUT account for over 50% of pediatric ESKD patients in this study from a tertiary referral center in Sudan.

#5114 THE GENOTYPE DISTRIBUTION IN A SINGLE-CENTRE COHORT OF PATIENTS WITH POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Polycystic kidney disease (PKD) is one of the most common causes of chronic kidney disease (CKD) and could lead to the end-stage kidney disease (ESKD) both in adulthood and in childhood. In the last few years many genes were discovered to be associated with PKD beyond the classical genes PKD1 and PKD2, that account for the majority of patients with ADPKD (Autosomal Dominant Polycystic Kidney Disease), and PKHD1 and DZIPIL that are responsible of ARPKD (Autosomal Recessive Polycystic Kidney Disease). The new genes are associated with different type of extra-renal involvement and with variable chance to develop CKD or ESKD. Thus, it is important for clinicians to define what mutation is involved in each patient to improve care in a context of precision medicine. We here describe a cohort of 65 consecutive patients followed at our PKD outpatient clinic who underwent the genetic analysis. Method We conducted a retrospective study of patients followed at our PKD outpatient clinic who underwent a genetic test for clinical reasons. We recorded why test was performed, with which modality and what was the result. If the analysis was positive we analyzed if only one or more genes were found mutated and if they belong to new genes described as being involved in PKD or if they are usually described in association with different diseases. Then, we collected demographic and clinical information (age, sex, renal function/presence of absence of ESKD) and the radiological description of kidneys in order to distinguish between typical and atypical PKDs. Results Among the 65 patients of our cohort 28 (43%) were males and 37 (57%) were females, the mean age was 56±18.6 years old; 20% had ESKD. They underwent genetic analysis for different reasons: 31 because of atypical PKD forms, 6 to define a suspected de novo mutation, 14 as a familiar screening and 14 for a better prognosis definition or when they approached the kidney transplant. The genetic analysis was conducted in two main ways: sequencing of PKD1 and PKD2 genes according to modern standards or exome sequencing. The first type of analysis was used for typical ADPKD forms whereas the second type was used when patients displayed an atypical presentation for both cysts distribution and kidney diameter (usually not enlarged kidneys with multiple bilateral cysts) and in two patients in which PKD1 and PKD2 sequencing was negative despite the PKD phenotype. We found that 25% of patients were negative, and the others are almost equally distributed between typical gene mutations and mutations in other genes (40% and 35% respectively) (Figure 1A). Of those with typical mutation, 81% was PKD1 positive and 19% PKD2 positive, a distribution that reflects that of literature (Figure 1B). Of those with other genes positivity: 52% had a DNAJB11 mutation, 17% a mutations in other PKD genes (ALG8, LRP5, PKHD1, COL4A1, IFT140), 32% had a mutation in genes usually associated with CAKUT (congenital anomalies of kidney and urinary tract) or with syndromic or extra-renal diseases (Figure 1C). 18 patients presented with multiple mutations, usually 2, in one case three and in another 4. Of them, the 22% had a double PKD1 mutation, while the others showed mutations in different genes associated with syndromic or extra-renal diseases (Figure 1D). Conclusion Our cohort revealed a wide variety of genetic mutations and also an almost equal distribution between typical genes and atypical/other genes. This could be the result of the small number of patients involved and of the monocentric design of the study (we have a cluster of patients with DNAJB11 belonging to the same small geographical area), but also of the larger inclusion of patients presenting with atypical PKDs. Unfortunately a 25% of patients remained genetically unresolved despite the use of exome sequencing.

Duplex collecting system with renal malrotation: an unusual combination

Both duplex collecting system and renal malrotation are congenital developmental anomalies of kidney. They usually present asymptomatic and accidentally diagnosed while patients undergo radiology examinations. We are reporting a case of a 33-year-old-male with a combination of duplex and malrotation kidney. Although these two are common anomalies of kidney, their combination is extremely rare. We found only two reports that had similar combined cases, so our case is the third reported.

Amniotic fluid content in children with kidney and urinary tract anomalies determines pre- and postnatal development

BackgroundRenal oligohydramnios (ROH) describes an abnormally low volume of amniotic fluid (AF) during pregnancy. ROH is mostly caused by congenital fetal kidney anomalies. The ROH diagnosis frequently implies an increased risk of peri- and postnatal fetal mortality and morbidity. The present study aimed to evaluate the impact of ROH on pre-and postnatal development in children with congenital kidney anomalies.MethodsThis retrospective study included 168 fetuses with anomalies in the kidney and urinary tract. Based on the amount of AF measured by ultrasound, patients were divided into three groups: normal amniotic fluid (NAF), amniotic fluid in the lower normal range (LAF), and ROH. These groups were compared with respect to prenatal sonographic parameters, perinatal outcomes, and postnatal outcomes.ResultsAmong the 168 patients with congenital kidney anomalies, 26 (15%) had ROH, 132 (79%) had NAF, and 10 (6%) had LAF. Of the 26 families affected by ROH, 14 (54%) decided to terminate pregnancy. Of 10 live-born children in the ROH group, 6 (60%) survived the observation time; of these, 5/6 presented with chronic kidney disease, stages I–III, at their last examination. The main differences in postnatal development between the ROH group and the NAF and LAF groups were: restricted height and weight gain, respiratory issues, complicated feeding, and the presence of extrarenal malformations.ConclusionsROH is not a mandatory indicator of severe postnatal kidney function impairment. However, children with ROH have complicated peri-and postnatal periods, due to the presence of concomitant malformations, which must be considered in prenatal care.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Disturbances in Switching between Canonical and Non-Canonical Wnt Signaling Characterize Developing and Postnatal Kidneys of Dab1-/- (yotari) Mice.

This study aims to determine the protein expression patterns of acetylated α-tubulin, inversin, dishevelled-1, Wnt5a/b, and β-catenin in developing (E13.5 and E15.5) and early postnatal (P4 and P14) kidneys of Dab1-/- (yotari) mice, their role in regulating the Wnt signaling pathway, and the possible relation to congenital anomalies of kidney and urinary tract (CAKUT). The analysis of target protein co-expression, observed in the renal vesicles/immature glomeruli, ampullae/collecting ducts, convoluted tubules, metanephric mesenchyme of developing kidneys, but proximal convoluted tubules, distal convoluted tubules and glomeruli of postnatal kidneys, was performed using double immunofluorescence and semi-quantitative methods. The overall expression of acetylated α-tubulin and inversin during normal kidney development increases with higher expression in yotari mice as the kidney acquires mature morphology. An increase in β-catenin and cytosolic DVL-1 levels, indicating a switch from non-canonical to canonical Wnt signaling, is found in the postnatal kidney of yotari mice. In contrast, healthy mouse kidney expresses inversin and Wnt5a/b in the postnatal period, thus activating non-canonical Wnt signaling. Target protein expression patterns in kidney development and the early postnatal period observed in this study could indicate that switching between canonical and non-canonical Wnt signaling is crucial for normal nephrogenesis, while the defective Dab1 gene product in yotari mice may promote CAKUT due to interfering with this process.

Predictive factors of advanced chronic kidney disease in children with congenital anomalies of kidney and urinary tract

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.

Subclinical C1q Nephropathy Combined with Possible Donor-Derived IgA Deposition in a 1-Year Kidney Allograft Biopsy: A Case Report

Few previous studies have reported immune-complex nephropathy that has not been classified as a specific phenotype in kidney allografts. We report a case of a de novo subclinical "full-house" pattern of deposition in a pediatric transplantation recipient with possible donor-derived IgA deposition. A five-year-old boy underwent living kidney transplantation due to congenital kidney and urinary tract anomalies. A one-hour implantation biopsy revealed IgA deposition. A four-month protocol biopsy finding showed less intense IgA deposition, in contrast with the one-hour biopsy, and trace para-mesangial deposits. A one-year protocol biopsy demonstrated a full-house deposition pattern and massive electron-dense deposits with minor glomerular changes. At the time of the one-year biopsy, kidney function was stable, with no urinalysis abnormalities. No evidence of systemic lupus erythematosus was observed in clinical and serologic examinations. Mesangial IgG, IgM, C3, and C1q deposition was codominant, and IgA deposition was weaker. We diagnosed this case as C1q nephropathy combined with remaining donor-derived IgA deposition. Few studies have reported C1q nephropathy in kidney allograft; further accumulation of cases is required. To distinguish between donor-derived and de novo glomerular lesions, it is important to assess the serial histologic findings of immunofluorescence and electron microscopy. Here, we report a rare case of subclinical C1q nephropathy with possible donor-derived IgA nephropathy.

PD37-01 THE CADHERIN-CATENIN COMPLEX IS CRUCIAL FOR THE INITIAL STEP OF NEPHRON FORMATION

You have accessJournal of UrologyCME1 Apr 2023PD37-01 THE CADHERIN-CATENIN COMPLEX IS CRUCIAL FOR THE INITIAL STEP OF NEPHRON FORMATION Balint Der, Helena Bugacov, Muskaan Singh, and Andrew P. McMahon Balint DerBalint Der More articles by this author , Helena BugacovHelena Bugacov More articles by this author , Muskaan SinghMuskaan Singh More articles by this author , and Andrew P. McMahonAndrew P. McMahon More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003335.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Congenital anomalies of the kidney and urinary tract contribute to a significant share of pre- and neonatal developmental abnormalities. In nephron formation, canonical Wnt-signaling induces mesenchymal nephron progenitor cells (NPCs) to aggregate and epithelialize forming the renal vesicle (RV), the nephron precursor. β-catenin is essential for the inductive process though the mechanism of morphological transition is not well understood (Park et al., 2007). We hypothesized that ß-catenin also directs RV formation through its critical role in cadherin mediated cell adhesion, the potential redundancy amongst cadherin members confounding earlier genetic studies (Dahl et al., 2002). METHODS: Using a chemically defined culture medium replicating in vivo NPC signaling, we examined the requirement for multiple cadherin adhesion complex components in the canonical Wnt signaling induced aggregation of induced NPCs in vitro. RESULTS: Removal of extracellular calcium, an essential ion in cadherin complexes, resulted in reversible loss of cell-cell contacts, consistent with a role for cadherin adhesion in the aggregation process. In vitro knockout of β-catenin inhibited the induction and aggregation of NPCs replicating the findings of the in vivo loss-of-function mouse experiments. Interestingly, the deletion of α-catenin phenocopied the results of β-catenin knockout experiments blocking cell aggregation providing further evidence for the role of the cadherin-catenin complex in the aggregation. To identify the cadherin members of the adhesion complex, we screened in vitro bulk RNA-seq. dataset and validated the presence of four cadherin proteins by immunofluorescent staining. The quadruple removal of in vitro expressed cadherins replicated the previously characterized phenomenon of inhibited aggregation of the NPCs. CONCLUSIONS: The aggregation of NPCs in vitro is exclusively mediated via the cadherin-catenin complex which models the initial step of nephrogenesis in vivo. A mechanistic insight into NPC aggregation fits within the larger framework of how a healthy kidney is formed and might explain the genetic background of certain congenital kidney anomalies. Source of Funding: National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK054364 Cell Interaction in Development of the Mammalian Kidney) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e986 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Balint Der More articles by this author Helena Bugacov More articles by this author Muskaan Singh More articles by this author Andrew P. McMahon More articles by this author Expand All Advertisement PDF downloadLoading ...

A decrease in the incidence of Shiga toxin-related hemolytic uremic syndrome as a cause of kidney transplantation at an argentine referral center.

In Argentina, Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC HUS), is the main cause of acute kidney injury and the second cause of end-stage renal disease (ESRD) in children. In recent decades, strategies have been implemented to reduce progression to ESRD, but it is not known whether the cumulative incidence of HUS requiring kidney transplantation (KTx) has decreased. We aimed to determine whether the cumulative incidence of STEC HUS in children undergoing KTx decreased and compared outcomes of HUS-related KTx vs. those related to other etiologies. All patients who underwent KTx at our institution were evaluated. The cohort was divided into quintiles (Q), and we compared the cumulative incidence of HUS-related KTx vs KTx due to other etiologies. A total of 1000 consecutive KTx were included. The cumulative incidence of HUS-related KTx was 11%. HUS was the second cause of KTx in Q1: 17% (1988-1995); Q2: 13.5% (1996-2003); Q3: 11.5% (2004-2009) and third cause in Q4: 10% (2010-2015) and Q5: 3% (2016-2021). The cumulative incidence of HUS-related KTx decreased in Q4 and Q5 compared to Q1, Q2, and Q3 and the decline was even steeper when comparing Q4 to Q5 (p:0.019). There was no difference in graft survival in patients with HUS vs. congenital anomalies of kidney and urinary tract (CAKUT) but better than in those with focal segmental glomerulosclerosis (FSGS). In this cohort, the cumulative incidence of HUS-related KTx decreased, which may have been due to the implementation of nephroprotective strategies.