Search Results (50)

Urinary tract infections (UTIs) are common bacterial infections in children. UTIs may be limited to the bladder or involve the kidneys with possible irreversible damage. Congenital abnormalities of the kidney and urinary tract (CAKUT) are often associated with UTIs; kidney scars have been considered a consequence of untreated UTIs but may be congenital. The mechanism by which bacteria produce inflammation in the urinary system has been intensively investigated. Diagnostic tools, including invasive imaging procedures, have been advocated in infants and small children with UTIs but are not necessary in most cases. Effective antibiotic drugs are available, and prophylactic treatment has been questioned. Several guidelines on UTIs are available, but a simple one for general practitioners is needed. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) represent a broad range of diseases with differing mechanisms, clinical presentations, and prognoses. With an estimated prevalence of between 4 and 60 per 10,000 births, CAKUT represents a sizable number of patients for pediatric and adult nephrologists as therapies have progressed, allowing longer life spans. Many CAKUT disorders are associated with genetic mutations, and with advances in genomic sequencing, these genes are being identified at an increasing rate. Understanding these mutations provides insight into these conditions’ molecular mechanisms and pathophysiology. In this article, we discuss the epidemiology, presentation, and outcomes of CAKUT in addition to our current understanding of genetic and molecular mechanisms in these diseases. Full article

Background and Objectives: This research explores the correlation between estimated glomerular filtration rates (eGFR) obtained using the bedside Schwartz equation, and renal scintigraphy in children with congenital kidney and urinary tract abnormalities (CAKUT). The objective is to enhance understanding and management of renal health in this demographic by analyzing kidney size-function relationships. Methods: A retrospective observational analysis was performed on 94 pediatric CAKUT patients at the “Louis Turcanu” Emergency Hospital for Children, Timisoara. Kidney function data, extracted from medical records, were evaluated using the Schwartz equation, renal scintigraphy, and the gold standard iohexol clearance. Ethical approval was secured for the study, which employed descriptive and inferential statistical methods, including t-tests and correlation coefficients, to compare eGFR values. Results: Significant variances were found in eGFRs across different body surface area (BSA) percentiles. For instance, the eGFR for the right kidney in the 25th–50th BSA percentile (102.02 ± 41.52 mL/min/BSA) was notably higher than that of the left (35.60 ± 26.05 mL/min/BSA; p = 0.01). The overall sample reflected a higher eGFR in the right kidney (76.03 ± 40.91 mL/min/BSA) compared to the left (57.46 ± 35.91 mL/min/BSA; p = 0.02). Additionally, a strong positive Pearson correlation (r = 0.80, p = 0.02) was found between scintigraphy and ultrasound measures in the 50th–75th percentiles for left renal percentiles, demonstrating consistent patterns across different evaluations of kidney function. Conclusions: This comparison indicates a complex relationship between eGFR values and kidney size, suggesting potential inaccuracies in standard bedside eGFR measurements for pediatric CAKUT patients. The findings underscore the necessity for accurate diagnostic tools specifically designed for pediatric applications and advocate for the integration of multiple diagnostic techniques to improve clinical management. Full article

Chronic kidney disease (CKD) is a widespread condition often resulting from multiple factors, including maternal influences. These risk factors not only heighten the likelihood of developing CKD but increase the risk of a preterm birth. Adverse events during nephrogenesis can disrupt kidney development, leading to a reduced number of nephrons. As survival rates for preterm infants improve, more individuals are living into adulthood, thereby elevating their risk of CKD later in life. This review aims to explore the connections between preterm birth, kidney development, and the increased risk of CKD, while proposing practical solutions for the future through a multidisciplinary approach. We examine human studies linking preterm birth to negative kidney outcomes, summarize animal models demonstrating kidney programming and reduced nephron numbers, and consolidate knowledge on common mechanisms driving kidney programming. Additionally, we discuss factors in the postnatal care environment that may act as secondary insults contributing to CKD risk, such as acute kidney injury (AKI), the use of nephrotoxic drugs, preterm nutrition, and catch-up growth. Finally, we outline recommendations for action, emphasizing the importance of avoiding modifiable risk factors and implementing early CKD screening for children born preterm. Together, we can ensure that advancements in kidney health keep pace with improvements in preterm care. Full article

The HNF1B gene, located on chromosome 17q12, encodes a transcription factor essential for the development of several organs. It regulates the expression of multiple genes in renal, pancreatic, hepatic, neurological, and genitourinary tissues during prenatal and postnatal development, influencing processes such as nephrogenesis, cellular polarity, tight junction formation, cilia development, ion transport in the renal tubule, and renal metabolism. Mutations that alter the function of Hnf1b deregulate those processes, leading to various pathologies characterized by both renal and extrarenal manifestations. The main renal diseases that develop are polycystic kidney disease, hypoplastic or dysplastic kidneys, structural abnormalities, Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), and electrolyte imbalances such as hyperuricemia and hypomagnesemia. Extrarenal manifestations include Maturity-Onset Diabetes of the Young (MODY), hypertransaminasemia, genital and urinary tract malformations, Autism Spectrum Disorder (ASD), and other neurodevelopmental disorders. Patients with HNF1B alterations typically carry either punctual mutations or a monoallelic microdeletion in the 17q12 region. Future research on the molecular mechanisms and genotype–phenotype correlations in HNF1B-related conditions will enhance our understanding, leading to improved clinical management, genetic counseling, monitoring, and patient care. Full article

Objective: A late mid-trimester fetal organ scan (lMTS) is recommended between 18 and 22 weeks of pregnancy. Evidence has been accumulating on the effectiveness of first-trimester anatomy scans. Early mid-trimester fetal scans (eMTSs; 14–17 weeks) may have the advantage of visualization of most organs, hence allowing earlier genetic assessment and decision making. Our aim is to examine the effectiveness of eMTSs in identifying fetal anomalies compared to lMTSs. Methods: A retrospective study was conducted based on data from the multidisciplinary prenatal diagnosis clinic in a tertiary center. During the study period (2011–2021), an out-of-pocket eMTS in a community setting was offered routinely to the general population. Women who had previously undergone an eMTS and were later assessed due to a fetal anomaly in our clinic were included in the study. The cohort was divided into two groups according to whether the anomaly had been detected during the eMTS. We then compared the groups for factors that may be associated with anomaly detection in eMTSs. We used t-tests and chi-square tests, for quantitative and qualitative variables, respectively, to determine variables related to eMTS anomaly detection, and logistic regression for multivariate analysis. Results: Of 1525 women assessed in our multidisciplinary clinic, 340 were included in the study. The anomaly detection rate of the eMTS compared to the lMTS was 59.1% The eMTS detection rates for specific organ systems were as follows: skeletal, 57%; cardiac, 52%; congenital anomalies of the kidneys and urinary tract (CAKUT), 44%; central nervous system, 32.4%; chest, 33%; and abdominal, 28%. In multivariate analysis, abnormal first-trimester screening (aOR 3.2; 95%CI 1.26–8.08) and multiple anomalies (aOR 1.86; 95%CI 1.02–3.37) were found to be associated with eMTS anomaly detection. Conclusions: The eMTS detection rate was nearly 60% and was most accurate in detecting skeletal, cardiac, and CAKUT anomalies. Since the eMTS was community-based, this rate likely reflects a “real-world” scenario. Our findings support consideration of performing an eMTS or first-trimester scan routinely for earlier diagnosis and decision making, as an adjunctive to lMTSs. Future studies will examine the cost-effectiveness of early scans. Full article

Congenital anomalies of the kidney and urinary tract (CAKUT) significantly contribute to pediatric morbidity, often necessitating ureterorenal surgery. This study explored the relationship between genetic mutations, renal surgery requirements, and prenatal, postnatal, and parental risk factors in children with CAKUT. A retrospective analysis of 651 children diagnosed with CAKUT included patient demographics, parental risk factors, ultrasound findings, genetic mutations, and surgical incidence. Antenatal ultrasounds showed normal findings in 32.1%, hydronephrosis in 46.9%, and other abnormalities in 21% of cases. Surgical intervention correlated with higher hydronephrosis reduction than non-intervention. Genetic mutations were identified in 5.4% of cases, with 24.6% requiring surgery. Low neonatal birth weight (odds ratio [OR] = 0.98, p < 0.001), advanced maternal age (OR = 1.06, p < 0.001), and postnatal abnormal ultrasound findings (OR = 2.62, p < 0.001) were associated with increased genetic mutation risks. Antenatal hydronephrosis (OR = 3.85, p < 0.001) and postnatal urinary tract infections (OR = 4.85, p < 0.001) increased the likelihood of surgical intervention. Neonatal birth weight, maternal age, and postnatal ultrasound findings were identified as independent risk factors for genetic mutations, while no significant link was found between these genetic factors and the need for surgery. Surgical needs were associated with urinary tract infections and antenatal hydronephrosis, indicating that timely surgical intervention may benefit these patients. Full article

Background/Objectives: Congenital anomalies of the kidney and urinary tract (CAKUT) are the main cause of chronic kidney disease (CKD) requiring renal replacement therapy (RRT) in children, being the leading cause (50–70%) of end-stage renal disease (ESRD) in children and young adults. Our study aimed to assess the natural evolution of various antenatally diagnosed renal malformations and to identify potential prognostic factors to guide the therapeutic management of patients with CAKUT. Methods: We conducted a retrospective study on 205 children with CAKUT. For each patient, analyzing their medical records, we established the nadir value of serum creatinine, defined as the lowest creatinine level during the first year of life. We assessed the value of nadir creatinine as a prognostic marker in patients with CAKUT, and using an ROC curve, we also determined a threshold value of nadir creatinine that predicted progression to ESRD. Results: The male-to-female ratio was 2.8 to 1. The mean gestational age at detection was 29.85 weeks (±6.71). A total of 36 patients (17.6%) had impaired renal function, of which 8 (3.9% of the total) progressed to ESRD. The mean nadir creatinine in patients with ESRD was 1.39 mg/dL. A nadir creatinine cut-off of 0.98 mg/dL had high sensitivity and specificity in identifying patients with progression to ESRD, with an AUC of 0.95 and a 95% confidence interval between 0.86 and 1.05 mg/dL. Conclusions: Our results support the value of nadir creatinine in predicting progression to ESRD, consistent with previously published data. Full article

Urinary tract infection (UTI) represents one of the most common bacterial infections in children, mainly caused by Gram-negative bacteria. Empirical antibiotic treatment is based on international and national guidelines for treating UTIs in children and is individualized with local antibiotic resistance patterns. The aim of this study is to bring a clear view of present-day particularities of UTIs in children. Methods: We analyzed 210 positive urine cultures identified in 141 pediatric patients admitted to the hospital over a 6-month period. Results: The majority of patients were females (57%) with a median age of 5 years (IQR 12), while male patients revealed a median age of 2 (IQR 7). Most patients originated from urban areas (53%). Only 18 patients (12.76%) were identified with underlying Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). Escherichia Coli was the most frequent pathogen. Increased antibiotic resistance was found in commonly-used antibiotics Ampicillin and Trimethoprim/Sulfamethoxazole, and in the case of patients with CAKUT. Suitable antibiotics for treating a Gram-negative UTI are aminoglycosides, Meropenem, third-generation Cephalosporins, and Nitrofurantoin. Vancomycin upholds efficacy in treating a Gram-positive pediatric UTI. Conclusion: Periodical analysis needs to be performed in order to constantly update clinicians on uropathogenic antibiotic resistance and optimal empirical treatment options. Full article

Kidney failures in infants are mostly caused by congenital anomalies of the kidney and urinary tract (CAKUT), which are among the most common congenital birth disorders worldwide when paired with cardiac abnormalities. People with CAKUT often have severe kidney failure as a result of a wide range of abnormalities that can occur alone or in conjunction with other syndromic disorders. In this study, we aimed to investigate the expression pattern of CAKUT candidate genes alpha-8 integrin (ITGA8) and Van Gogh-like 2 (VANGL2) in fetal tissues of healthy and CAKUT-affected kidneys using immunohistochemistry and immunofluorescence. We found that under CAKUT circumstances, the expressions of ITGA8 and VANGL2 are changed. Additionally, we showed that VANGL2 expression is constant during fetal aging, but ITGA8 expression varies. Moreover, compared to normal healthy kidneys (CTRL), ITGA8 is poorly expressed in duplex kidneys (DKs) and dysplastic kidneys (DYS), whereas VANGL2 is substantially expressed in dysplastic kidneys (DYS) and poorly expressed in hypoplastic kidneys (HYP). These results point to VANGL2 and ITGA8 as potential prognostic indicators for CAKUT malformations. Further research is necessary to explore the molecular mechanisms underlying this differential expression of ITGA8 and VANGL2. Full article

Our study examines the immunoexpression patterns of Megalin, Cubilin, Caveolin-1, Gipc1 and Dab2IP in the embryonic development (E) and postnatal (P) mouse kidney, with a focus on differentiating patterns between wild-type (wt) and yotari, Dab1^−/− (yot) mice. Immunofluorescence revealed raised immunoexpression of receptors Megalin and Cubilin at the ampulla/collecting ducts and convoluted tubules across all developmental stages, with the most prominent immunoexpression observed in the convoluted tubules and the parietal epithelium of the Bowman’s capsule. Quantitative analysis showed a higher percentage of Megalin and Cubilin in wt compared to yot mice at E13.5. Co-expression of Megalin and Cubilin was observed at the apical membrane of convoluted tubules and the parietal layer of the Bowman’s capsule. The staining intensity of Megalin varied across developmental stages, with the strongest reactivity observed at the ampulla and collecting ducts at embryonic day (E) 13.5 in wt mice. In contrast, Caveolin-1 exhibited high immunoexpression in the metanephric mesenchyme, blood vessels, and the border area between the metanephric mesenchyme and renal vesicle, with a decrease in immunoexpression as development progressed. Gipc1 showed diffuse cytoplasmic staining in metanephric mesenchyme, convoluted tubules and collecting ducts, with significant differences in immunoexpression between wild-type and yot mice at both investigated embryonic time points. Dab2IP immunofluorescent staining was most prominent in renal vesicle/glomeruli and ampulla/collecting ducts at E13.5, with mild staining intensity observed in the distal convoluted tubules postnatally. Our findings elucidate distinct immunoexpression of patterns and potential parts of these proteins in the development and function of the kidney, highlighting the importance of further investigation into their regulatory mechanisms. Full article

The purpose of this study was to evaluate the spatiotemporal immunoexpression pattern of microtubule-associated protein 1 light chain 3 beta (LC3B), glucose-regulated protein 78 (GRP78), heat shock protein 70 (HSP70), and lysosomal-associated membrane protein 2A (LAMP2A) in normal human fetal kidney development (CTRL) and kidneys affected with congenital anomalies of the kidney and urinary tract (CAKUT). Human fetal kidneys (control, horseshoe, dysplastic, duplex, and hypoplastic) from the 18th to the 38th developmental week underwent epifluorescence microscopy analysis after being stained with antibodies. Immunoreactivity was quantified in various kidney structures, and expression dynamics were examined using linear and nonlinear regression modeling. The punctate expression of LC3B was observed mainly in tubules and glomerular cells, with dysplastic kidneys displaying distinct staining patterns. In the control group’s glomeruli, LAMP2A showed a sporadic, punctate signal; in contrast to other phenotypes, duplex kidneys showed significantly stronger expression in convoluted tubules. GRP78 had a weaker expression in CAKUT kidneys, especially hypoplastic ones, while normal kidneys exhibited punctate staining of convoluted tubules and glomeruli. HSP70 staining varied among phenotypes, with dysplastic and hypoplastic kidneys exhibiting stronger staining compared to controls. Expression dynamics varied among observed autophagy markers and phenotypes, indicating their potential roles in normal and dysfunctional kidney development. Full article

Approximately half of the cases of chronic kidney disease (CKD) in childhood are caused by congenital anomalies of the kidney and urinary tract (CAKUT). Specific genes were identified as having significant importance in regard to the underlying genetic factors responsible for the CAKUT phenotype, and in our research, we focused on analyzing and comparing the expression levels of ectodysplasin A2 receptor (EDA2R), protocadherin9 (PCDH9), and TNF receptor-associated factor 7 (TRAF7) proteins in the cortex and medulla of healthy control kidneys during developmental phases 2, 3, and 4. We also performed an analysis of the area percentages of the mentioned proteins in the cortical and medullary sections of healthy embryonic and fetal kidneys compared to those affected by CAKUT, including duplex kidneys (DK), horseshoe kidneys (HK), hypoplastic kidneys (HYP), and dysplastic kidneys (DYS). We found that the CAKUT candidate gene proteins EDA2R, PCDH9, and TRAF7 are all expressed during normal human kidney development stages. In DYS, the expression of EDA2R was higher than in normal kidneys, likely due to EDA2R’s role in apoptosis, which was upregulated in specific cases and could possibly contribute to the formation of DYS. The expression of PCDH9 was lower in HK, which can be attributed to the possible role of PCDH9 in cell migration suppression. Decreased PCDH9 expression is linked to increased cell migration, potentially contributing to the development of HK. The level of TRAF7 expression was reduced in all examined kidney disorders compared to normal kidneys, suggesting that this reduction might be attributed to the crucial role of TRAF7 in the formation of endothelium and ciliogenesis, both of which are essential for normal kidney development. Further research is required to ascertain the function of these proteins in both the typical development of the kidney and in CAKUT. Full article

Duplex kidney is a urinary tract anomaly commonly associated with a wide range of primary and secondary parenchymal structural abnormalities. We present a unique comparison of US and MRI findings with histopathology following partial resection of duplex kidneys due to nephropathy. We examined a group of 21 children with duplex kidneys who were qualified for heminephrectomy (24 kidney units (KU)). All patients underwent US and MRI prior to the surgery. The imaging results were compared with histopathologic findings. In 21/24 KU, dysplastic changes were found on histopathology, including all with obstructive nephropathy and 7/10 specimens with refluxing uropathy. The loss of corticomedullary differentiation on US and increased signal on T2-weighted images (T2WI) on MRI were the imaging findings that best correlated with fibrosis. In children with megaureter, there were no statistical differences in histopathological findings between primary megaureter, megaureter with ureterocele, and megaureter with ectopia (p > 0.05). The extent of dysplasia of the affected pole correlated negatively with residual function in MRI. Kidney dysplasia and inflammation in the kidney with obstructive nephropathy are the most important histopathologic findings of this study. US is a valuable screening tool, and MRI enables morphologic and functional assessments of the nephropathy in duplex kidneys. Full article

Congenital anomalies affecting the kidneys present significant challenges in pediatric nephrology, needing precise methods for assessing renal function and guiding therapeutic intervention. Bedside Schwartz formula with the cystatin-C-based Full Age Spectrum formula and Chronic Kidney Disease in Children (CKiD) U 25 formula used in estimating glomerular filtration rate (eGFR) and also to assess if the eGFR in association with kidney length percentiles can be a monitoring parameter for the progression of chronic kidney disease in children with congenital anomalies of the kidney and urinary tract (CAKUT). A total of 64 pediatric patients (median age at diagnostic was 12 months with an interquartile range of 2 to 60) were diagnosed with congenital anomalies in the kidney and urinary tract between June 2018 and May 2023 at “Louis Turcanu” Emergency Hospital for Children in Timisoara, Romania. Baseline characteristics, CAKUT types, associated pathologies, CKD staging, and eGFR using creatinine and cystatin C were analyzed. The mean age at the moment of examination was 116.50 months; (65, 180). Chronic kidney disease staging revealed a predominance of patients in CKD stages G1 and A1. Analysis of eGFR methods revealed a small mean difference between eGFR estimated by creatinine and cystatin C, with a moderate-strong positive correlation observed between the eGFR and ultrasound parameters. Using cystatin-C-based formulas for eGFR, in conjunction with ultrasound measurements, may offer reliable insights into renal function in pediatric patients with congenital anomalies affecting the kidney and urinary tract. However, the economic aspect must be taken into consideration because cystatin C determination is approximately eight times more expensive than that of creatinine. An interdisciplinary approach is crucial for managing patients with CAKUT. Full article