Maternal diseases and congenital anomalies of the kidney and urinary tract in offspring: a cohort study.

BACKGROUND: Congenital anomalies of the kidneys and urinary tract (CAKUT) are the most common cause of prenatally diagnosed developmental malformation. This study aimed to assess the relationship between maternal diseases and CAKUT in offspring. METHODS: This retrospective study enrolled all pregnant women registered from January 2020 to December 2022 at one medical center. Medical information on maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease was collected. Based on the records of ultrasound scanning during the third trimester, the diagnosis was classified as isolated urinary tract dilation (UTD) or kidney anomalies. Multivariate logistic regression was performed to establish models to predict antenatal CAKUT. RESULTS: Among the 19,656 pregnant women, perinatal ultrasound detected suspicious CAKUT in 114 (5.8/1000) fetuses, comprising 89 cases with isolated UTD and 25 cases with kidney anomalies. The risk of antenatal CAKUT was increased in the fetuses of mothers who experienced gestational diabetes, thyroid dysfunction, neuropsychiatric disease, anemia, ovarian and uterine disorders. A prediction model for isolated UTD was developed utilizing four confounding factors, namely gestational diabetes, gestational hypertension, maternal thyroid dysfunction, and hepatic disease. Similarly, a separate prediction model for kidney anomalies was established based on four distinct confounding factors, namely maternal thyroid dysfunction, gestational diabetes, disorders of ovarian/uterine, and kidney disease. CONCLUSIONS: Isolated UTD and kidney anomalies were associated with different maternal diseases. The results may inform the clinical management of pregnancy and highlight potential differences in the genesis of various subtypes of CAKUT.

Vesico-ureteral reflux diagnosis after initial kidney abscess: Results from a Paediatric Tertiary Hospital.

AIMS: Guidelines regarding voiding cystourethrogram (VCUG) indications following a paediatric kidney abscess are lacking. This study evaluates vesicoureteral reflux (VUR) prevalence and outcome after a first kidney abscess. METHODS: This retrospective study included all children presenting to a tertiary paediatric reference centre with de-novo kidney abscesses from 2011 to 2022, diagnosed through imaging (ultrasonography or computed tomography). VCUG's clinical utility was assessed by exploring outcomes related to interventions. RESULTS: Among the 17 patients (median age 9 months, IQR; 6 months-6 years), VCUG identified VUR in 7 (41%; 95% CI: 18-65%), including two with grade IV-V. Median abscess size was 19 mm (IQR; 14-27). 7/8 (88%) children with DMSA scan presented scars, including 4 with hypofunctioning (20%-44%), and one with a non-functioning kidney. Scarring on the DMSA scan was similar regardless of identified VUR. Six children had subsequent pyelonephritis. Three of the remaining 11 had grade I-III and two IV-V VUR. Surgery was required in four children overall: three for recurrent pyelonephritis and one for high-grade VUR and scars. CONCLUSION: Among initial kidney abscess cases, 41% had VUR, similar to children experiencing their first uncomplicated pyelonephritis. VCUG results guided antibiotic prophylaxis but not surgical decisions. We suggest considering VCUG following recurrent pyelonephritis/kidney abscess and/or kidney scarring.

Secondary pseudohypoaldosteronism: a 15-year experience and a literature review.

BACKGROUND: Secondary pseudohypoaldosteronism (S-PHA) is a rare condition resulting from renal tubular resistance to aldosterone in children with urinary tract infection (UTI) and/or nephrourological malformations. It is characterized by nonspecific symptoms but with the potential for life-threatening complications. We aim to evaluate the clinical manifestations, diagnostic approach, and therapeutic interventions in children with S-PHA, along with a review of recent publications. METHODS: A retrospective observational descriptive study was conducted on S-PHA cases diagnosed over the last 15 years at a tertiary pediatric nephrology unit. The literature for the last 10 years was reviewed. RESULTS: Twelve patients (10 males, 6 days to 6 months) were identified. Weight loss was the main reason for consultation (50%). Ninety-two percent of patients had an underlying nephrourological pathology and 62% concomitant confirmed UTI. Seven out of 12 children were admitted to the PICU. A subsequent extrapontine myelinolysis was observed in one patient as neurological sequelae. Twenty-one articles related to S-PHA have been identified on PubMed and Embase. CONCLUSIONS: S-PHA should be considered in infants under 6 months of age with UTI and/or CAKUT. Obstructive anomalies and vesicoureteral reflux can be found, affecting both unilateral and bilateral systems. Early medical and surgical interventions are crucial and require close monitoring to avoid iatrogenic complications.

Expression of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) Candidate Genes EDA2R, PCDH9, and TRAF7 in Normal Human Kidney Development and CAKUT.

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.

Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease.

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) from human pluripotent stem cells (hPSCs). Molecular analyses demonstrated that cultured iNPCs closely resemble primary human NPCs. iNPCs generated nephron organoids with minimal off-target cell types and enhanced maturation of podocytes relative to published human kidney organoid protocols. Surprisingly, the NPC culture medium uncovered plasticity in human podocyte programs, enabling podocyte reprogramming to an NPC-like state. Scalability and ease of genome editing facilitated genome-wide CRISPR screening in NPC culture, uncovering genes associated with kidney development and disease. Further, NPC-directed modeling of autosomal-dominant polycystic kidney disease (ADPKD) identified a small-molecule inhibitor of cystogenesis. These findings highlight a broad application for the reported iNPC platform in the study of kidney development, disease, plasticity, and regeneration.

Insights into Kidney Dysplasia in Duplex Kidneys: From Radiologic Diagnosis to Histopathologic Understanding.

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.

Surgical intervention and long-term renal outcomes of congenital ureteropelvic junction obstruction in a young adult cohort.

PURPOSE: To evaluate the impact of surgical intervention on long-term renal outcomes for adult patients with congenital ureteropelvic junction obstruction (UPJO). METHODS: We queried service members diagnosed with UPJO from the United States Military Health System electronic health records from 2005 to 2020. We assessed demographic, laboratory, radiology, surgical intervention, and outcome data. We evaluated the impact of surgical intervention on renal function based on the estimated glomerular filtration rate (eGFR), hypertension (HTN, defined as any prescription for blood pressure [BP] medication and/or average of two BP readings ≥ 130/80 mmHg more than 2 weeks apart), and changes in renal excretory function on radionuclide scans. RESULTS: We identified 108 individuals diagnosed with congenital UPJO; mean follow-up of 7 years. Mean age at diagnosis was 25 years; 95% male; 69% White, 15% Black. At diagnosis, median BP was 130/78 mmHg and mean eGFR 93 ml/min/1.73m2. Subsequently, 85% had pyeloplasty and 23% had stent placement. There were no significant differences in mean eGFR pre- and post-intervention (94 vs. 93 ml/min/1.73m2, respectively; p = 0.15) and prevalence of defined HTN (59% vs. 61%, respectively; p = 0.20). Surgical intervention for right-sided UPJO significantly reduced the proportion of patients with delayed cortical excretion (54% pre vs. 35% post, p = 0.01) and T½ emptying time (35 min vs. 19 min, p = 0.009). Similar trends occurred with left-sided UPJO but were not significant. CONCLUSION: Surgical intervention was not associated with significant differences in the long-term outcomes of kidney function and HTN prevalence in our young adult cohort. However, renal excretory function improved on radionuclide scans.

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

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

Copy number variation analysis identifies MIR9-3 and MIR1299 as novel miRNA candidate genes for CAKUT.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) represent a frequent cause of pediatric kidney failure. CNVs, as a major class of genomic variations, can also affect miRNA regions. Common CNV corresponding miRNAs (cCNV-miRNAs) are functional variants regulating crucial processes which could affect urinary system development. Thus, we hypothesize that cCNV-miRNAs are associated with CAKUT occurrence and its expressivity. METHODS: The extraction and filtering of common CNVs, identified in control samples deposited in publicly available databases gnomAD v2.1 and dbVar, were coupled with mapping of miRNA sequences using UCSC Genome Browser. After verification of the mapped miRNAs using referent miRBase V22.1, prioritization of cCNV-miRNA candidates has been performed using bioinformatic annotation and literature research. Genotyping of miRNA gene copy numbers for MIR9-3, MIR511, and MIR1299, was conducted on 221 CAKUT patients and 192 controls using TaqMan™ technology. RESULTS: We observed significantly different MIR9-3 and MIR1299 gene copy number distribution between CAKUT patients and controls (Chi-square, P = 0.006 and P = 0.0002, respectively), while difference of MIR511 copy number distribution showed nominal significance (Chi-square, P = 0.027). The counts of less and more than two of MIR1299 copy numbers were more frequent within CAKUT patients compared to controls (P = 0.01 and P = 0.008, respectively) and also in cohort of patients with anomalies of the urinary tract compared to controls (P = 0.016 and P = 0.003, respectively). CONCLUSIONS: Copy number variations of miRNA genes represent a novel avenue in clarification of the inheritance complexity in CAKUT and provide potential evidence about the association of common genetic variation with CAKUT phenotypes.

Early diagnosis of solitary functioning kidney: comparing the prognosis of kidney agenesis and multicystic dysplastic kidney.

BACKGROUND: Individuals with congenital solitary functioning kidney (SFK) are at an increased risk of kidney damage. According to some studies, the risk is higher in unilateral kidney agenesis (UKA) than in unilateral multicystic dysplastic kidney (UMCDK). We hypothesized that with early detection of children with UKA and UMCDK, there would be no difference in the presence of hypertension, proteinuria, and reduced glomerular filtration rate (GFR) between UKA and UMCDK. METHODS: Based on a long-term follow-up protocol, we evaluated a cohort of 160 children followed from birth for SFK (84 with UKA and 76 with UMCDK) detected by prenatal or routine neonatal ultrasound screening. Hypertension, proteinuria, and reduced GFR were monitored as markers of kidney damage. We compared the characteristics and outcomes of the subgroups of children with UKA and UMCDK. RESULTS: GFR was reduced in 42 (26.2%) children, of whom 41 showed only mild reduction. Hypertension and proteinuria were found in 22 (13.8%) and 14 (8.8%) children, respectively. Combined kidney damage was present in 57 (35.6%) children. The UMCDK and UKA subgroups differed in GFR at final examination, with UMCDK patients being significantly more likely to have normal GFR compared to UKA patients (82% vs. 67%; p = 0.039). CONCLUSIONS: One third of the children showed signs of SFK damage, albeit mild. Patients with UKA had reduced GFR significantly more often than those with UMCDK, but did not differ in the rates of hyperfiltration injury or congenital anomalies of the kidneys and urinary tract (CAKUT) in SFK.

GEN1 as a risk factor for human congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. METHODS: In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. RESULTS: Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. CONCLUSION: Overall, our findings indicated GEN1 as a risk factor for human CAKUT.

Use of ChatGPT in Urology and its Relevance in Clinical Practice: Is it useful?

ABSTRACT Purpouse: One of the many artificial intelligence based tools that has gained popularity is the Chat-Generative Pre-Trained Transformer (ChatGPT). Due to its popularity, incorrect information provided by ChatGPT will have an impact on patient misinformation. Furthermore, it may cause misconduct as ChatGPT can mislead physicians on the decision-making pathway. Therefore, the aim of this study is to evaluate the accuracy and reproducibility of ChatGPT answers regarding urological diagnoses. Materials and Methods: ChatGPT 3.5 version was used. The questions asked for the program involved Primary Megaureter (pMU), Enuresis and Vesicoureteral Reflux (VUR). There were three queries for each topic. The queries were inserted twice, and both responses were recorded to examine the reproducibility of ChatGPT's answers. Afterwards, both answers were combined. Finally, those rwere evaluated qualitatively by a board of three specialists. A descriptive analysis was performed. Results and Conclusion: ChatGPT simulated general knowledge on the researched topics. Regarding Enuresis, the provided definition was partially correct, as the generic response allowed for misinterpretation. For VUR, the response was considered appropriate. For pMU it was partially correct, lacking essential aspects of its definition such as the diameter of the dilatation of the ureter. Unnecessary exams were suggested, for Enuresis and pMU. Regarding the treatment of the conditions mentioned, it specified treatments for Enuresis that are ineffective, such as bladder training. Therefore, ChatGPT responses present a combination of accurate information, but also incomplete, ambiguous and, occasionally, misleading details.

Kidney collecting system anatomy applied to endourology - a narrative review

ABSTRACT Objective: To evaluate the surgical anatomy of the kidney collecting system through a narrative review of the literature, highlighting its importance during diagnosis and its approach during surgical procedures for the treatment of renal stones. Material and Methods: We carried out a review about the anatomy of the kidney collecting system. We analyzed papers published in the past 40 years in the databases Pubmed, Embase and Scielo, and we included only papers in English and excluded case reports, editorials and opinions of specialists. Results: Renal collecting system could be divided in four groups: A1 - kidney midzone (KM), drained by minor calyx that are dependent on the superior or the inferior caliceal groups; A2 - KM drained by crossed calyx, one draining into the superior caliceal group and another draining into the inferior caliceal group; B1 - KM drained by a major caliceal group independent of both the superior and inferior groups; and B2 - KM drained by minor calyx entering directly into the renal pelvis. Some details and anatomic variations of the collecting system are related to clinical and radiological aspects, particularly perpendicular calyces, interpyelocalyx space, position of calyces in relation to renal border, classification of the renal collecting system, infundibular diameter and the angle between the lower infundibulum and renal pelvis. Conclusion: The knowledge of intra-renal collecting system divisions and variations as the angle between the renal pelvis and lower infundibula, position of the calices in relationship with renal edge and the diameter and position of the calyces are important for the planning of minimally invasive renal surgeries.

Evaluation of differential renal function in children - a comparative study between magnetic resonance urography and dynamic renal scintigraphy.

BACKGROUND: Urinary system anomalies, both congenital and acquired, constitute a relatively common clinical problem in children. The main role of diagnostic imaging is to determine early diagnosis and support therapeutic decisions to prevent the development of chronic renal disease. The aim of this study was to evaluate the utility of magnetic resonance urography (MRU) in assessment of urinary system in children, by comparing differential renal function calculated using MRU with dynamic renal scintigraphy (DRS). MATERIALS AND METHODS: The study group consisted of 46 patients aged 1 week to 17 years (median 7 (0.5; 13) years, 17 (37%) girls, 29 (63%) boys), who underwent dynamic renal scintigraphy due to various clinical reasons. All participants underwent MRU, which was used to measure differential renal function. Functional analysis was performed using dedicated external software (CHOP-fMRU and pMRI without prior knowledge of DRS results. MRU results acquired using pMRI were assessed for inter and intraobserver agreement. RESULTS: Statistical analysis of the results showed excellent agreement between MRU and DRS in measuring differential renal function with Pearson correlation coefficient 0.987 for CHOP-fMRU and 0.971 for pMRI, p < 0.001. Interclass correlation coefficient (ICC) for these programs was 0.987 (95% CI 0.976-0.993) and 0.969 (95% CI 0.945-0.983) respectively, p < 0.001. The Bland-Altman 95% limits of agreement for CHOP-fMRU results vs. DRS was - 6.29-5.50 p.p. and for pMRI results vs. DRS - 9.15-9.63 p.p. The differential renal function measurements calculated in pMRI showed excellent intraobserver and interobserver agreement with ICC 0.996 (95% CI 0.994-0.998) and 0.992 (95% CI 0.986-0.996) respectively, p < 0.001. CONCLUSIONS: The study showed no significant differences between magnetic resonance urography and dynamic renal scintigraphy in calculating differential renal function. It indicates high utility of MRU in the evaluation of urinary system in children.

Brain and spine malformations and neurodevelopmental disorders in a cohort of children with CAKUT.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20-30% of all birth defects and are often associated with extra-renal malformations. We investigated the frequency of brain/spine malformations and neurological features in children with CAKUT. METHODS: We reviewed the clinico-radiological and genetic data of 199 out of 1,165 children with CAKUT evaluated from 2006 to 2023 (99 males, mean age at MRI 6.4 years) who underwent brain and/or spine MRI. Patients were grouped according to the type of CAKUT (CAKUT-K involving the kidney and CAKUT-H involving the inferior urinary tract). Group comparisons were performed using χ2 and Fisher exact tests. RESULTS: Brain/spine malformations were observed in 101/199 subjects (50.7%), 8.6% (101/1165) of our CAKUT population, including midbrain-hindbrain anomalies (40/158, 25.3%), commissural malformations (36/158, 22.7%), malformation of cortical development (23/158, 14.5%), Chiari I anomaly (12/199, 6%), cranio-cervical junction malformations (12/199, 6%), vertebral defects (46/94, 48.9%), caudal regression syndrome (29/94, 30.8%), and other spinal dysraphisms (13/94, 13.8%). Brain/spine malformations were more frequent in the CAKUT-K group (62.4%, p < 0.001). Sixty-two subjects (62/199, 31.2%) had developmental delay/intellectual disability. Neurological examination was abnormal in 40/199 (20.1%). Seizures and/or electroencephalographic anomalies were reported in 28/199 (14%) and behavior problems in 19/199 subjects (9%). Developmental delay/intellectual disability was more frequent in kidney dysplasia (65.2%) and agenesis (40.7%) (p = 0.001). CONCLUSIONS: We report a relative high frequency of brain/spine malformations and neurodevelopmental disorders in children with CAKUT who underwent MRI examinations in a tertiary referral center, widening the spectrum of anomalies associated with this condition.

A founder variant expands the phenotype of WNT7B-related PDAC syndrome.

Pulmonary hypoplasia, Diaphragmatic anomalies, Anophthalmia/microphthalmia, and Cardiac defects (PDAC) syndrome is a genetically heterogeneous multiple congenital malformation syndrome. Although pathogenic variants in RARB and STRA6 are established causes of PDAC, many PDAC cases remain unsolved at the molecular level. Recently, we proposed biallelic WNT7B variants as a novel etiology based on several families with typical features of PDAC syndrome albeit with variable expressivity. Here, we report three patients from two families that share a novel founder variant in WNT7B (c.739C > T; Arg247Trp). The phenotypic expression of this variant ranges from typical PDAC features to isolated genitourinary anomalies. Similar to previously reported PDAC-associated WNT7B variants, this variant was found to significantly impair WNT7B signaling activity further corroborating its proposed pathogenicity. This report adds further evidence to WNT7B-related PDAC and expands its variable expressivity.

SALL4 deletion and kidney and cardiac defects associated with VACTERL association.

Congenital anomalies of the kidney and urinary tract (CAKUT) can be a part of the VACTERL association, which represents the non-random combination of the following congenital anomalies: vertebral anomalies, anal anomalies, cardiac anomalies, tracheal-esophageal anomalies, kidney anomalies, and limb anomalies. VACTERL association is generally considered to be a non-genetic condition. Exceptions include a patient with a heterozygous nonsense SALL4 variant and anal stenosis, tetralogy of Fallot, sacro-vertebral fusion, and radial and thumb anomalies. SALL4 encodes a transcription factor that plays a critical role in kidney morphogenesis. Here, we report a patient with VACTERL association and a heterozygous 128-kb deletion spanning SALL4 who presented with renal hypoplasia, radial and atrio-septal defects, and patent ductus arteriosus. The present report of SALL4 deletion, in addition to a previously reported patient with VACTERL association phenotype and SALL4 nonsense mutation, further supports the notion that SALL4 haploinsufficiency can lead to VACTERL association.

Use of ChatGPT in Urology and its Relevance in Clinical Practice: Is it useful?

PURPOUSE: One of the many artificial intelligence based tools that has gained popularity is the Chat-Generative Pre-Trained Transformer (ChatGPT). Due to its popularity, incorrect information provided by ChatGPT will have an impact on patient misinformation. Furthermore, it may cause misconduct as ChatGPT can mislead physicians on the decision-making pathway. Therefore, the aim of this study is to evaluate the accuracy and reproducibility of ChatGPT answers regarding urological diagnoses. MATERIALS AND METHODS: ChatGPT 3.5 version was used. The questions asked for the program involved Primary Megaureter (pMU), Enuresis and Vesicoureteral Reflux (VUR). There were three queries for each topic. The queries were inserted twice, and both responses were recorded to examine the reproducibility of ChatGPT's answers. Afterwards, both answers were combined. Finally, those rwere evaluated qualitatively by a board of three specialists. A descriptive analysis was performed. RESULTS AND CONCLUSION: ChatGPT simulated general knowledge on the researched topics. Regarding Enuresis, the provided definition was partially correct, as the generic response allowed for misinterpretation. For VUR, the response was considered appropriate. For pMU it was partially correct, lacking essential aspects of its definition such as the diameter of the dilatation of the ureter. Unnecessary exams were suggested, for Enuresis and pMU. Regarding the treatment of the conditions mentioned, it specified treatments for Enuresis that are ineffective, such as bladder training. Therefore, ChatGPT responses present a combination of accurate information, but also incomplete, ambiguous and, occasionally, misleading details.

Kidney collecting system anatomy applied to endourology - a narrative review.

OBJECTIVE: To evaluate the surgical anatomy of the kidney collecting system through a narrative review of the literature, highlighting its importance during diagnosis and its approach during surgical procedures for the treatment of renal stones. MATERIAL AND METHODS: We carried out a review about the anatomy of the kidney collecting system. We analyzed papers published in the past 40 years in the databases Pubmed, Embase and Scielo, and we included only papers in English and excluded case reports, editorials and opinions of specialists. RESULTS: Renal collecting system could be divided in four groups: A1 - kidney midzone (KM), drained by minor calyx that are dependent on the superior or the inferior caliceal groups; A2 - KM drained by crossed calyx, one draining into the superior caliceal group and another draining into the inferior caliceal group; B1 - KM drained by a major caliceal group independent of both the superior and inferior groups; and B2 - KM drained by minor calyx entering directly into the renal pelvis. Some details and anatomic variations of the collecting system are related to clinical and radiological aspects, particularly perpendicular calyces, interpyelocalyx space, position of calyces in relation to renal border, classification of the renal collecting system, infundibular diameter and the angle between the lower infundibulum and renal pelvis. CONCLUSION: The knowledge of intra-renal collecting system divisions and variations as the angle between the renal pelvis and lower infundibula, position of the calices in relationship with renal edge and the diameter and position of the calyces are important for the planning of minimally invasive renal surgeries.

A preliminary study of the miRNA restitution effect on CNV-induced miRNA downregulation in CAKUT.

BACKGROUND: The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro. METHODS: Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets). RESULTS: Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts. CONCLUSIONS: Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.