Congenital Anomalies Of Kidney And Urinary Tract 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.

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.

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.

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.

#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.

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.

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.

Early-in-Life Serum Aldosterone Levels Could Predict Surgery in Patients with Obstructive Congenital Anomalies of the Kidney and Urinary Tract: A Pilot Study.

The aim of the study was to evaluate whether serum aldosterone levels or plasmatic renin activity (PRA) measured early in life (1-3 months) could predict a future surgical intervention for obstructive congenital anomalies of kidney and urinary tract (CAKUT). Twenty babies aged 1-3 months of life with suspected obstructive CAKUT were prospectively enrolled. The patients underwent a 2-year follow-up and were classified as patients needing or not needing surgery. In all of the enrolled patients, PRA and serum aldosterone levels were measured at 1-3 months of life and were evaluated as predictors of surgery by receiver-operating characteristic (ROC) curve analysis. Patients undergoing surgery during follow-up showed significantly higher levels of aldosterone at 1-3 months of life compared to those who did not require surgery (p = 0.006). The ROC curve analysis of the aldosterone for obstructive CAKUT needing surgery showed an area under the ROC curve of 0.88 (95%CI = 0.71-0.95; p = 0.001). The aldosterone cut-off of 100 ng/dL presented 100% sensitivity and 64.3% specificity and predicted surgery in 100% of cases. The PRA at 1-3 months of life was not a predictor of surgery. In conclusion, serum aldosterone levels at 1-3 months could predict the need for surgery during obstructive CAKUT follow-up.

CAKUT: A Pediatric and Evolutionary Perspective on the Leading Cause of CKD in Childhood

The global prevalence of chronic kidney disease (CKD) is increasing rapidly, due to increasing environmental stressors through the life cycle. Congenital anomalies of kidney and urinary tract (CAKUT) account for most CKD in children, with a spectrum that can lead to kidney failure from early postnatal to late adult life. A stressed fetal environment can impair nephrogenesis, now recognized as a significant risk factor for the development of adult CKD. Congenital urinary tract obstruction is the leading cause of CKD due to CAKUT and can itself impair nephrogenesis as well as contribute to progressive nephron injury. Early diagnosis by ultrasonography in fetal life by an obstetrician/perinatologist can provide important information for guiding prognosis and future management. This review focuses on the critical role played by the pediatrician in providing timely evaluation and management of the patient from the moment of birth to the transfer to adult care. In addition to genetic factors, vulnerability of the kidney to CKD is a consequence of evolved modulation of nephron number in response to maternal signaling as well as to susceptibility of the nephron to hypoxic and oxidative injury. Future advances in the management of CAKUT will depend on improved biomarkers and imaging techniques.

Renal-hepatic-pancreatic dysplasia type 2: Perinatal lethal condition or a multisystemic disorder with variable expressivity.

Renal-hepatic-pancreatic dysplasia type 2 (RHPD2) is a rare condition that has been described in the literature disproportionately in perinatal losses. The main features of liver and kidney involvement are well described, with cardiac malformations and cardiomyopathy adding additional variation to the phenotype. Many patients reported are within larger cohorts of congenital anomalies of kidney and urinary tract (CAKUT) or liver failure, and with minimal phenotypic and clinical course data. An independent series of phenotypes and prognosis was aggregated from the literature. In this literature review, we describe an additional patient with RHPD2, provide a clinical update on the oldest known living patient, and report the cumulative phenotypes from the existing published patients. With now examining the 17 known patients in the literature, 13 died within the perinatal period-pregnancy to one year of life. Of the four cases living past the first year of life, one case died at 5 years secondary to renal failure, the other at 30 months secondary to liver and kidney failure. Two are currently alive and well at one year and 13 years. Two cases have had transplantation with one resulting in long-term survival. These patients serve to expand the existing phenotype of RHPD2 as a perinatal lethal condition into a pediatric disorder with variable expressivity. Additionally, we introduce the consideration of transplantation and outcomes within this cohort and future patients.

Prenatal diagnosis and molecular cytogenetic analyses of a paternal inherited deletion of 1q23.3 encompassing PBX1 gene

BackgroundPatients with deletions involving the long arm of chromosome 1 are rare. The PBX1 gene is located on chromosome 1q23.3. PBX1 encodes a transcription factor which promotes protein–protein interaction and plays a crucial role in several developmental processes. PBX1 haploinsufficiency had been reported to lead syndromic congenital anomalies of kidney and urinary tract (CAKUT) in humans.Case presentationIn this research, a 24-year-old woman (gravida 1, para 0) underwent amniocentesis at 22 weeks’ gestation because of a horseshoe kidney of the fetus on prenatal ultrasound.ResultsChromosomal microarray analysis (CMA) from this family revealed a 1.14 Mb paternal inherited deletion on chromosome 1q23.3, spanning from position 163,620,000 to 164,760,000 (hg19). Trio whole-exome sequencing (WES) showed heterozygous deletions in exons 1–2 of the PBX1 in fetal and paternal samples. At the 3-year follow-up, the baby did not have an abnormal phenotype except a horseshoe kidney.ConclusionWe provide a detailed description of the phenotype in a family with paternal inherited deletion of 1q23.3 encompassing exons 1–2 of the PBX1 gene. Combination of karyotype analysis, CMA, WES, prenatal ultrasound and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.

Risk factors for childhood chronic kidney disease: a population-based study.

The population-based prevalence and risk factors of childhood chronic kidney disease (CKD) are not well-defined. We ascertained childhood CKD epidemiology and perinatal risk factors, based on a large computerized medical record database that covers most of southern Israel's population. Pre- and post-natal records of 79,374 eligible children (with at least one serum creatinine test) born during 2001-2015 were analyzed. "Ever-CKD" was defined as ≥ 2 estimated glomerular filtration rate (eGFR) values < 60ml/min/1.73 m2 beyond age 2years, more than 3months apart. The last CKD status was determined on March 2019. Of 82 (0.1%) patients with ever-CKD, 35 (42.7%) had their first abnormal eGFR identified already at age 2years. In multiple logistic regression analysis, congenital anomalies of kidney and urinary tract (CAKUT)-related diagnoses, glomerulopathy, maternal oligohydramnios, small for gestational age, prematurity (under 34weeks), post-term delivery, and small for gestational age at birth were significant risk factors for ever-CKD (odds ratio (95% confidence interval): 44.34(26.43-74.39), 64.60(32.42-128.70), 5.54(3.01-10.19), 2.02(1.25-3.28), 4.45(2.13-9.28), 2.96(1.28-6.86 and 2.02(1.25-3.28), respectively). Seventy children with ever-CKD (85.4%) had a depressed eGFR (< 90ml/min/1.73 m2) on the last assessment (current-CKD), yielding a prevalence of 882/million. CKD is more prevalent among children in southern Israel than previously reported, even after excluding those with aborted-CKD. Prenatal conditions increase the risk to develop CKD in childhood. Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information.

A study of the 20-year evolution of antimicrobial resistance patterns of pediatric urinary tract infections in a single center.

Febrile urinary tract infections (UTIs) are important bacterial infections in children but increasingly difficult to treat due to antimicrobial resistance. We performed a retrospective analysis of the prevalence of uropathogens in hospitalized children with a febrile UTI between 2000 and 2019 in our university hospital to get more insight into trend and determinants of antimicrobial resistance over time. There were 1010 hospitalizations in children with a median age of 1.1years. Thirty-six percent had an abnormal ultrasound and/or the presence of vesico-ureteral reflux, defined as CAKUT. Escherichia coli was the most prevalent pathogen (76%). However, there was an increasing prevalence towards other gram-negative organisms over time, and these pathogens were more common in children with congenital anomalies of kidney and urinary tract (CAKUT) (OR 4.26 (3.14-5.78), p < 0.001). E. coli strains demonstrated an increase in resistance against amoxicillin clavulanic acid (AMC) over time from 16% (2000-2004) to 36% (2015-2019) with an average increase of 2.0%/year; this was + 1.1%/year for third-generation cephalosporin. Multivariate analysis demonstrated that prior antibiotic use was an additional risk factor for antimicrobial resistance in E. coli. Nevertheless, increasing resistance was also observed in children without reported previous antibiotic treatment (+ 1.9%/year, p = 0.04). Conclusion: We observed a significant pattern of increasing antimicrobial resistance of E. coli within a relatively short period of time, making it increasingly difficult to treat pediatric UTIs. This pattern was also seen in children without underlying risk factors (recent antibiotic treatment or structural urological disease). This is indicative for a larger problem in the general population and an important threat to our current standard of health care. What is Known: •Escherichia coli is the most frequent pathogen in pediatric urinary tract infections. •There is an increasing antimicrobial resistance against commonly used antibiotics in urinary tract infections. What is New: •The first 20-year retrospective, longitudinal study on characteristics of the microorganisms of pediatric urinary tract infections in a single center. •A 1-2% yearly increase in antimicrobial resistance, not only in children with congenital anomalies of the kidneys or recent antibiotic treatment but also in children without risk factors.

Genetic Basis of Congenital Anomalies of Kidney and Urinary Tract

Congenital anomalies of kidney and urinary tract (CAKUT) is a group of abnormalities affecting the kidneys or other structures of the urinary tract that include ureters, urinary bladder and urethra. CAKUT include renal agenesis or hypodysplasia, multicystic dysplastic kidney, ureteropelvic junction obstruction, duplication of the pelvis, ureter, and/or kidney, congenital megaureter, ureterovesical junction obstruction, vesicoureteral reflux and posterior urethral valves. Those results from abnormal development of the urinary system and is present from birth (congenital), although the abnormality may not become apparent until later in life. The clinical spectrum of CAKUT has significant impact on long-term patient survival. We observed that the causes of CAKUT are complex, usually combination of genetic and environmental factors contribute to the developmental abnormalities of kidney and urinary tract in foetus. The genetic factors involved in most cases of CAKUT are unknown; however, syndromic CAKUT is caused by changes in the genes associated with the particular syndrome. Variations in the same genes can also underlie some cases of isolated CAKUT. This review paper aims to discuss genetic basis of CAKUT, i.e., identifying different genes involved in syndromic and non-syndromic CAKUT. Modern genetic testing facilities can provide a precise diagnosis that can help individualize clinical care by screening for specific complications, facilitate medical decision making, and provide better genetic counseling.&#x0D; CBMJ 2022 January: vol. 11 no. 01 P: 69-74

Ventricular Septal defect (VSD) as an extra renal manifestation in Congenital Anomalies of Kidney and Urinary Tract (CAKUT) Syndrome: A rare Case report

Ventricular Septal defect (VSD) as an extra renal manifestation in Congenital Anomalies of Kidney and Urinary Tract (CAKUT) Syndrome: A rare Case report

Renal Hypoplasia: Case Literature Review

Introduction: Congenital anomalies of kidney and urinary tract (CAKUT) presents a broad range of disorders including abnormal renal parenchymal development, disrupted parenchymal development, abnormalities of lower urinary tract, urinary collecting system. The knowledge of these anomalies will help the clinicians and surgeons during the procedures of kidney. The purpose of this article is to present one of the cases of renal hypoplasia and the review that highlights renal hypoplasia cases. Methodology: A vertical incision has been made in midline from xiphoid process to pubic symphysis encircling the umbilicus, another incision from pubic symphysis laterally up to the anterior superior iliac tubercle along the iliac crest to expose the abdominal cavity. Details of the position suprarenal gland and the upper poles of the kidneys and external appearance of kidneys in situ were noted. The arrangement of the attached structures such as the hilum with structures passing through, ureter, bladder, abdominal aorta and the inferior vena cava were also noted and recorded. Observation and Result: The size of the left kidney was found small in comparison to right kidney. Coronal section of left kidney also showed a smaller number of renal pyramids, major calyces and minor calyces. Conclusion: The knowledge of anatomical variations of urinary system has a significant role for clinicians and surgeons for diagnosing diseases including congenital anomalies, radiological interpretations, procedures, surgical interventions and management of clinical conditions. KEY WORDS: Renal Hypoplasia, Congenital Anomalies Of Kidney And Ureter, Cadavers, Dissection.

Genetic Testing and Biomarkers as Predictive Tools for Congenital Anomalies of Kidney and Urinary Tract (CAKUT)

Genetic Testing and Biomarkers as Predictive Tools for Congenital Anomalies of Kidney and Urinary Tract (CAKUT)

Antibiotic Resistance Patterns of Uropathogens Causing Urinary Tract Infections in Children with Congenital Anomalies of Kidney and Urinary Tract.

Background: Urinary tract infections (UTI) are common in children worldwide. Congenital anomalies of kidney and urinary tract (CAKUT) increase the risk of UTI and consequently antibiotic resistance. Antibiotic resistance represents an important public health issue worldwide. We aimed to evaluate the local trend in terms of bacterial uropathogen resistance in the western part of Romania in children with CAKUT and UTI. Methods: 252 children with CAKUT were admitted to our hospital over a five-year period. Of them, 91 developed at least one UTI episode, with a total number of 260 positive urine cultures. We collected data about age at diagnosis of CAKUT, sex, origin environment, type and side of CAKUT, number of UTIs, type of uropathogen, and uropathogens antibiotic resistance. Results: Distribution of uropathogens was Escherichia coli (38.84%), Klebsiella spp. (21.15%), Enterococcus spp. (15.76%), Proteus spp. (8.07%), Pseudomonas spp. (8.07%), Enterobacter spp. (2.3%), other Gram-negative bacteria (2.3%), and other Gram-positive bacteria (3.45%). High antibiotic resistance was detected for ampicillin, amoxicillin, and second-generation cephalosporins. Escherichia coli presented high resistance for cefepime and ceftriaxone. Pseudomonas spp. remained susceptible to amikacin, quinolones, and colistin. Vancomycin, teicoplanin, linezolid, and piperacillin/tazobactam remained effective in treating Gram-positive UTI. Conclusions: High antibiotic resistance was identified for frequently used antibiotics. Lower antibiotic resistance was observed for some broad-spectrum antibiotics. Understanding uropathogens’ antibiotic resistance is important in creating treatment recommendations, based on international guidelines, local resistance patterns, and patient particularities.

Genomics Integration Into Nephrology Practice

Rationale & ObjectiveThe etiology of kidney disease remains unknown in many individuals with chronic kidney disease (CKD). We created the Mayo Clinic Nephrology Genomics Clinic to improve our ability to integrate genomic and clinical data to identify the etiology of unexplained CKD.Study DesignRetrospective study.Setting & ParticipantsAn essential component of our program is the Nephrology Genomics Board which consists of nephrologists, geneticists, pathologists, translational omics scientists, and trainees who interpret the patient’s clinical and genetic data. Since September 2016, the Board has reviewed 163 cases (15 cystic, 100 glomerular, 6 congenital anomalies of kidney and urinary tract (CAKUT), 20 stones, 15 tubulointerstitial, and 13 other).Analytical ApproachTesting was performed with targeted panels, single gene analysis, or analysis of kidney-related genes from exome sequencing. Variant classification was obtained based on the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology guidelines.ResultsA definitive genetic diagnosis was achieved for 50 families (30.7%). The highest diagnostic yield was obtained in individuals with tubulointerstitial diseases (53.3%), followed by congenital anomalies of the kidney and urological tract (33.3%), glomerular (31%), cysts (26.7%), stones (25%), and others (15.4%). A further 20 (12.3%) patients had variants of interest, and variant segregation, and research activities (exome, genome, or transcriptome sequencing) are ongoing for 44 (40%) unresolved families.LimitationsPossible overestimation of diagnostic rate due to inclusion of individuals with variants with evidence of pathogenicity but classified as of uncertain significance by the clinical laboratory.ConclusionsIntegration of genomic and research testing and multidisciplinary evaluation in a nephrology cohort with CKD of unknown etiology or suspected monogenic disease provided a diagnosis in a third of families. These diagnoses had prognostic implications, and often changes in management were implemented.

Urinary biomarkers as point-of-care tests for predicting progressive deterioration of kidney function in congenital anomalies of kidney and urinary tract: trefoil family factors (TFFs) as theemerging biomarkers.

Children with congenital anomalies of kidney and urinary tract (CAKUT) are at high risk of progressive deterioration of kidney function and further developing stage5 chronic kidney disease (CKD5), even after a successful surgery. This prospective study was designed to determine whether urinary biomarkers can predict progressive deterioration of kidney function in children with CAKUT. The study included 50 consecutive children, aged < 14 years, who were diagnosed with congenital uropathies (PUV, VUR, and PUJO) and 20 age-matched controls. Examination of four urinary biomarkers, i.e., trefoil family factors (TFF) 1 and 3, neutrophil gelatinase-associated lipocalin (NGAL) and microalbuminuria (MALB) was done at the beginning of follow-up. Kidney function was assessed, at the beginning and after 12-months of follow-up, by technetium-99m diethylene triamine pentaacetic acid (DTPA) and technetium-99m dimercaptosuccinic acid (DMSA) scans. Progressive deterioration in the kidney function was defined as a fall in the GFR from ≥ 60 to < 60 ml/min/1.73 m2 on comparing the baseline and latest DTPA scans; and/or new-onset cortical scar/scars or increase in the size of previous scar/scars on serial DMSA scans. Group 1 and group 2 included children without and with progressive functional deterioration respectively. The median (IQR) age of children with CAKUT and controls was 3 (1.5-5) and 2.3 (1.2-3.6) years, respectively, and showed no significant difference (p = 0.29). Median concentrations of TFF1, TFF3, NGAL, and microalbumin in patients were 44.5, 176.5, 281.2, and 15.5 mcg/gCr, respectively, and were significantly elevated as compared to controls (p < 0.05). Children belonging to group 2 had significantly higher concentration of biomarkers as compared to those in group 1. TFF3 was found have the highest AUC (0.9198) on ROC curve for predicting progressive functional deterioration. Urinary TFFs, NGAL, and microalbumin significantly correlate with progressive deterioration of kidney function in children harboring CAKUT. TFF3, with the strongest prediction of functional deterioration, is an emerging peptide showing sufficient potential to be included in the biomarker panel. Graphical abstract.