Mitochondrial viability in neurogenic bladder urothelium after sigmoidocolocystoplasty. Implications for persistent vesicoureteral reflux.

PURPOSE: We investigated whether inflammatory cell infiltration (ICI), fibrosis, and mitochondrial viability of the neurogenic bladder urothelium are involved in the mechanism of persistent vesicoureteral reflux (VUR) after sigmoidocolocystoplasty (SCP). METHODS: Bladder biopsies obtained 1994-2023 from 62 neurogenic bladder patients were examined by hematoxylin and eosin for ICI, Masson's trichrome for fibrosis, and immunofluorescence for urothelial growth differentiation factor 15 (GDF15; a mitochondrial stress-responsive cytokine) (positive/negative) and heat shock protein 60 (HSP60; a mitochondrial matrix marker) (strong ≥ 50%/weak≤ 50%) expression. GDF15 + /weak HSP60 indicated compromised mitochondrial viability. Cystometry measured neobladder compliance/capacity. RESULTS: Mean ages (years) at SCP and bladder biopsies were 9.4 ± 4.6 and 14.2 ± 7.1, respectively. VUR was present in 38/62 patients (51 ureters) at SCP and resolved with SCP alone in 4/38 patients, with SCP and ureteroneocystostomy in 17/38, and persisted in 17/38. Fibrosis was significantly denser in GDF15 + (n = 24)/weak HSP60 (n = 31) compared with GDF15- (n = 38)/strong HSP60 (n = 31) (p < 0.001 and p < 0.01, respectively). Differences in ICI were significant for GDF15 + vs. GDF15- (p < 0.05) but not for HSP60. Patients with VUR after SCP had higher incidence of GDF15 + /weak HSP60 compared with cases without VUR (p < 0.05 and p < 0.001, respectively). CONCLUSION: Viability of mitochondria appears to be compromised with possible etiologic implications for VUR persisting after SCP.

Expression Profiles of ITGA8 and VANGL2 Are Altered in Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).

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.

Immunoexpression Pattern of Autophagy-Related Proteins in Human Congenital Anomalies of the Kidney and Urinary Tract.

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.

Novel anti-reflux ureteral skirt: proof of concept in a Yorkshire-Landrace pig model.

INTRODUCTION: Stents with anti-reflux properties have been previously described in various studies but not widely adopted. We designed, constructed and tested a novel umbrella-looking anti-reflux skirt on a double J stent at the level of the ureteral orifice in a previous ex-vivo study. This study serves as a proof of concept of testing this prototype in a porcine model. METHODS: 3 Yorkshire-Landrace pigs were put under general anaesthesia. Conventional bilateral retrograde stenting with white-colored double-J stents were performed. Deployment of anti-reflux skirt was performed unilaterally. Capsaicin mixed with methylene blue and saline were instilled in the bladder. Both stents were removed and methylene blue stain were inspected to assess the level of reflux. Bilateral stenting was performed again and stents/skirt prototype were left in-situ for 1 week. The procedure was repeated on Day 7 to re-test the anti-reflux property of the prototype after ureteral dilatation. RESULTS: Intraluminal reflux was evident, with methylene blue stain seen on the inner surface of the stents. Extraluminal reflux was proved with blue stain seen on the outer surface of the stents, both in undilated and dilated ureters. Study also proved the anti-reflux property of the skirt as the blue stain didn't go beyond the skirt, whereas the contralateral stent was stained up to proximal ureter. CONCLUSION: In this porcine in-vivo study, we elucidated that reflux occurred were both intraluminal and extraluminally. As a proof of concept, it also showed the anti-reflux property of a novel ureteral skirt.

Comparison and clinical analysis of antibiotics and endoscopic injection for vesicoureteral reflux in children.

PURPOSE: This study evaluated the outcome of pediatric patients with primary vesicoureteral reflux (VUR) and compared of the treatments between continued antibiotic prophylaxis (CAP) and endoscopic injection. METHODS: The clinical data of children diagnosed with primary vesicoureteral reflux from March 2015 to June 2020 who were treated with antibiotics or endoscopic injection were reviewed. Antibiotic was the first-chosen treatment after the diagnosis of VUR in children. Endoscopic treatment consisted of injection of dextran hyaluronic acid copolymer (DX/HA) into the ureteral opening under direct cystoscopy guidance. RESULTS: Fifty-two children (35 males, 17 females) were included in this study, and for a total 90 ureters (14 unilateral, 38 bilateral) were diagnosed with vesicoureteral reflux by Voiding cystourethrography (VCUG). Twenty-two children were treated with antibiotics (8 unilateral, 14 bilateral), for a total of 36 ureters; thirty children were treated by endoscopic injection (6 unilateral, 24 bilateral), for a total of 54 ureters. The injection surgery took 36 ± 17 min including duration of general anesthesia and circumcision and the hospital stay was 2.3 ± 1.3 days. All male patients underwent circumcision simultaneously. There were no drug and allergic reactions in the antibiotic group, and no postoperative complications occurred in the injection group. With 23 months (13-63 months) of mean follow-up, the resolution rate, defined as radiological disappearance of VUR, was 36.1% (13/36) in the antibiotic group and 57.4% (31/54) in the injection group (P = 0.048).Two cases of bilateral reflux in the injection group required a second injection before resolution could be achieved. Thus, the overall success rate of injection was 64.8% (35/54). 9 cases (9/18, 50%) in the antibiotic group had renal scars on DMSA scans, while this was seen in 20 cases (20/23, 86.9%) in the injection group. There was a statistically significant difference between the two groups (P = 0.010).The positive rates of ultrasound between the antibiotic group and the injection group were 45.5% (10/22) and 80.0% (24/30), respectively. There was a statistically significant difference between the two groups in positive rates of ultrasound (P = 0.010). CONCLUSIONS: Endoscopic injection is easy to operate with short surgical time and hospital stay, so it is a safe and feasible treatment. For the treatment of primary vesicoureteral reflux in children, the radiological resolution rate of endoscopic injection is better than antibiotic therapy. In this study, the presence of kidney scars on DMSA and the dilated of the collecting system on ultrasound are the indications for endoscopic injection.

Predictors of reflux persistence after endoscopic dextranomer/hyaluronic Acid copolymer injection in pediatric patients with Vesicoureteral reflux: short-term results.

This study aims to investigate the factors effective in predicting the persistence of reflux after the first subureteric transurethral injection (STING) of dextranomer/hyaluronic acid copolymer in pediatric patients with vesicoureteral reflux. The data of patients without a previous history of surgery to treat vesicoureteral reflux and who underwent STING for the first time between September 2011 and November 2020 were investigated retrospectively. After considering exclusion criteria, of 199 patients, 127 patients and 180 renal units were suitable for inclusion. A renal unit-based evaluation was made. Age < 61 months (univariate: p = 0.001, multivariate: p = 0.015, HR: 2.352 (1.181-4.686), OR (95% CI)), moderate reflux level (grade 3) (univariate: p < 0.001, multivariate: p = 0.019, HR: 2.703 (1.177-6.209), OR (95% CI)), DRF (differential renal function) < 45 (univariate: p = 0.020, multivariate: p = 0.047, HR: 1.992 (1.009-3.935), OR (95% CI)), and UDR (ureteral diameter ratio) > 0.15 (univariate: p < 0.001, multivariate: p = 0.005, HR: 2.786 (1.368-5.672), OR (95% CI)) were found predictors of reflux persistence after STING surgery both univariate and multivariate analysis. High reflux level (grade 4-5) was statistically significant in univariate analysis (p < 0.001) but not statistically significant in multivariate analysis (p = 0.215). In our study, UDR and DRF were found to be factors affecting reflux persistence. UDR and DRF should be considered in order to predict reflux resolution in patients who will undergo STING.

The Extended Utilization of Bulking Agents in Pediatric Urology.

PURPOSE OF REVIEW: Traditional surgical management for urinary incontinence and vesicoureteral reflux often requires complex reconstructive surgery and extended hospitalizations. Since the introduction of endoscopic bulking agents in 1973, there has been increasing interest in the use of endoscopic injection (EI) and bulking for the treatment of a variety of pediatric urologic disorders. The purpose of this review is to summarize the most recent literature addressing the use of bulking agents in pediatric urology. RECENT FINDINGS: The most recent literature has focused primarily on the use of EI of bulking agents at the bladder neck for the treatment of urinary incontinence. Other uses of EI of bulking agents has focused on the treatment of vesicoureteral reflux (VUR) in patients with anatomic abnormalities or treatment of incontinence catheterizable channels. The development of advanced techniques for endoscopic injection along with safe, stable bulking agents has allowed for the treatment of a variety of urologic conditions. This minimally invasive procedure offers an additional tool for the pediatric urologist's armamentarium in the treatment of urinary incontinence and VUR.

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.

Urodynamic Abnormalities in Children with Primary Bilateral Vesicoureteral Reflux.

BACKGROUND: Bilateral vesicoureteral reflux (VUR) has been associated with poor long-term prognosis, and research focusing exclusively on its effect on urinary bladder function is lacking. This study aims to assess the urodynamic characteristics of children with bilateral VUR and identify factors influencing renal function. METHODS: A retrospective analysis was performed on children diagnosed with bilateral VUR who underwent urodynamic examination in the outpatient department of our institution from January 2019 to January 2023. All patients underwent comprehensive assessments, including voiding cystourethrography, urinary system ultrasound and urodynamic examination, to analyse the urodynamic features associated with different clinical characteristics. RESULTS: The study included 148 children with bilateral VUR, amongst whom 92 (62.2%) exhibited urodynamic abnormalities, including idiopathic detrusor overactivity (DO) in 30 cases (20.3%) and dysfunctional voiding (DV) in 58 cases (39.2%). DV was prevalent in children under 5 years of age, whereas idiopathic DO was predominantly observed in children older than 2 years of age. Children older than 5 years of age exhibited a trend towards reduced bladder volume, whereas those younger than 2 years of age often had increased bladder volume and residual urine. Multivariate analysis identified bilateral severe VUR as an independent risk factor for abnormal estimated glomerular filtration rate. CONCLUSIONS: DV tends to be more common in younger children with larger bladder volumes and increased residual urine than in older children. By contrast, older children are more susceptible to idiopathic DO associated with smaller bladder volumes than younger children. Bilateral severe reflux increases the likelihood of renal functional abnormalities, which appear to be a consequence of congenital scarring rather than abnormalities in bladder function.

DLG1 functions upstream of SDCCAG3 and IFT20 to control ciliary targeting of polycystin-2.

Polarized vesicular trafficking directs specific receptors and ion channels to cilia, but the underlying mechanisms are poorly understood. Here we describe a role for DLG1, a core component of the Scribble polarity complex, in regulating ciliary protein trafficking in kidney epithelial cells. Conditional knockout of Dlg1 in mouse kidney causes ciliary elongation and cystogenesis, and cell-based proximity labeling proteomics and fluorescence microscopy show alterations in the ciliary proteome upon loss of DLG1. Specifically, the retromer-associated protein SDCCAG3, IFT20, and polycystin-2 (PC2) are reduced in the cilia of DLG1-deficient cells compared to control cells. This phenotype is recapitulated in vivo and rescuable by re-expression of wild-type DLG1, but not a Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)-associated DLG1 variant, p.T489R. Finally, biochemical approaches and Alpha Fold modelling suggest that SDCCAG3 and IFT20 form a complex that associates, at least indirectly, with DLG1. Our work identifies a key role for DLG1 in regulating ciliary protein composition and suggests that ciliary dysfunction of the p.T489R DLG1 variant may contribute to CAKUT.

Genetic determinants of renal scarring in children with febrile UTI.

BACKGROUND: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. METHODS: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy. RESULTS: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes. CONCLUSIONS: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs.

The effect of well-managed lower urinary tract dysfunction on the success rate of endoscopic subureteric injection for low-moderate vesicoureteral reflux.

AIM: We aimed to study the presence of lower urinary tract dysfunction (LUTD) and those objective parameters obtained from voiding diary (VD), uroflowmetric (UF) and postvoiding residual urine (PVR) and voiding dysfunction symptom score (VDSS) as possible factors effecting the success rate on STING to correct VUR. MATERIALS AND METHODS: Children who underwent STING for the first time due to low-moderate (I-III) grade of VUR were evaluated retrospectively. All children diagnosed with VUR were routinely evaluated for LUTD with VD, UF, PVR and VDSS. Children with LUTD were treated with urotherapy and appropriate medical treatment. Each system with VUR was accepted a renal unit and divided into two groups according to the presence of postoperative VUR: Group 1 no VUR, and Group 2 unresolved VUR. Demographic characteristics, DMSA scintigraphy findings, PVR, VDSS and parameters of VD and UF were compared. RESULTS: 80 children (73 (91.3%) girl, 7 (8.8%) boy) with a total of 112 unit were detected. There were 93 (83%) units in group 1 and 19 (17%) in group 2. No difference was observed in voiding frequency and urinary incontinence in VD, flow pattern, maximum flow rate, MBC/EBC maximum bladder capacity/expected bladder capacity in UF, PVR and VDSS between two groups. 21 (26.25%) children were diagnosed and treated for LUTD and STING was successful in 21 (84%) of 25 units. CONCLUSION: We believe that effectively treated preoperative LUTD provides comparable STING success rate for correcting low- to moderate-grade vesicoureteral reflux (VUR) in the short term.

Vantris vs. deflux for treatment of paediatric vesicoureteral reflux: Efficacy and obstruction risk.

INTRODUCTION: The aim was to compare the efficacy of polyacrylate polyalcohol copolymer (PPC) injections and dextranomer/hyaluronic acid (Dx/Ha) injections for the endoscopic treatment of vesicoureteral reflux in children. MATERIAL: This retrospective cohort study included 189 young patients who had endoscopic treatment for vesicoureteral reflux from January 2012 to December 2019 in our center. Among them, 101 had PCC injections and 88 had Dx/Ha injections. Indications for treatment were vesicoureteral reflux with breakthrough urinary tract infection or vesicoureteral reflux with renal scarring on dimercaptosuccinic acid (DMSA) renal scan. Endoscopic injection was performed under the ureteral meatus. Early complications, recurrence of febrile urinary tract infection and vesicoureteral reflux after endoscopic injection, ureteral obstruction and reintervention were evaluated and compared between groups. RESULTS: Endoscopic treatment was successful in 90.1% of patients who had PPC injection and in 82% of patients who had Dx/Ha injection. Four patients presented a chronic ureteral obstruction after PPC injection, one with a complete loss of function of the dilated kidney. One patient in the Dx/Ha group presented a postoperative ureteral dilatation after 2 injections. CONCLUSION: Despite a similar success rate after PPC and Dx/Ha injections for endoscopic treatment of VUR, there may be a greater risk of postoperative ureteral obstruction after PPC injections. The benefit of using PPC to prevent febrile UTI and renal scarring in children with low-grade VUR does not seem to outweigh the risk of chronic ureteral obstruction.

Risk factors of congenital anomalies of the kidney and urinary tract (CAKUT): Exposure to mobile phones during pregnancy.

Background/aim: Congenital anomalies of the kidney and urinary tract(CAKUT) are the leading causes of childhood chronic kidney disease (CKD). The etiology of most of the cases is thought to be multifactorial. In this study, risk factors for CAKUT and the effect of mobile phone-related electromagnetic field (EMF) exposure during pregnancy were investigated. Materials and methods: Fifty-seven cases and 57 healthy controls under 2 years of age were included and their mothers were subjected to a questionnaire. Groups were compared for parents' demographics, pregestational (chronic disease, body mass index, use of the folic acid supplements) and antenatal variables (gestational disease, weight gain during pregnancy,) and exposures during pregnancy. To assess mobile phone-related radiation exposure, all participants were asked about their daily call time, the proximity of the phone when not in use, and the models of their mobile phones. The specific absorption rate (SAR) of the mobile phones and the effective SAR value (SAR × call time) as an indicator of EMF exposure were recorded. Results: Excess weight gain according to BMI during pregnancy was related to an increased risk of CAKUT (p=0.012). Folic acid use before pregnancy was protective for CAKUT (p = 0.028). The call time of mothers of the CAKUT group was significantly longer than the control (p = 0.001). An association was observed between higher effective SAR values and increased risk of CAKUT (p = 0.03). However the proximity of the mobile phone to the mother's body when not in use was not found as a risk factor. Conclusion: The etiology of CAKUT is multifactorial. Our results suggest that prolonged phone call and higher EMF exposure during pregnancy increases the risk of CAKUT in the offspring.

First episode of febrile urinary tract infection in children, detection and risk factors of kidney scarring: A prospective cohort study.

AIMS: This prospective study aimed to evaluate the characteristics and findings of children who presented with acute pyelonephritis (APN) and to determine the independent risk factors for kidney scarring. MATERIAL AND METHODS: Patients who satisfied the following criteria were enrolled in the study: first known episode of APN; at least two of the following findings: fever ≥ 38.5 °C, white blood cell count ≥ 10,000/mm3, erythrocyte sedimentation rate ≥ 20 mm/h, C-reactive protein ≥ 20 mg/dL; absence of congenital abnormalities or other kidney and systemic diseases, except vesicoureteral reflux (VUR); no APN relapses until the time of kidney scar detection. 99mTc-Dimercaptosuccinic acid kidney scintigraphy (99mTc-DMSA) was performed at admission, along with a kidney ultrasound. Follow-up 99mTc-DMSA took place after 6 months. Radiographic cystourethrography for VUR detection and grading was performed 1 month after the acute infection. RESULTS: We enrolled 70 children in the study. The kidney ultrasound failed to diagnose more than half of the cases of APN. VUR was found in 21.5% of children. 75% had findings of APN in the acute phase through 99mTc-DMSA, while in the second 99mTc-DMSA, there was a complete remission in 68% of them. Scars were observed more frequently in older children, children with VUR grade ≥ III, and children not on antibiotic prophylaxis. CONCLUSION: VUR did not appear to be associated with the first episode of APN, and children older than 1 year of age had a higher risk of scarring. Antibiotic prophylaxis may prevent kidney scarring due to host immunomodulatory effects, but more studies are needed so that conclusions can be drawn.

Robotic-assisted native pyeloureterostomy with indocyanine green, after kidney transplantation.

INTRODUCTION: Postoperative ureteral strictures and vesicoureteral reflux after ureteroneocystostomy for kidney transplant can be managed by endoscopic procedures like balloon dilation and endoscopic injections. Complicated/recurrent cases, however, are usually managed by reconstructive surgery. We hereby highlight our technique of robotic-assisted native pyeloureterostomy with indocyanine green (ICG). MATERIALS AND SURGICAL TECHNIQUE: A 57-year-old woman, diagnosed with grade 4 vesicoureteral reflux on her transplanted kidney, was considered a candidate for ureteral reimplantation. After an endoscopic part, where the ICG is inserted into the renal pelvis, we proceed with the robotic native pyeloureterostomy. The renal pelvis of the transplanted kidney was identified with the help of the ICG in firefly mode. After the dissection of the graft pelvis, we performed a tension-free pyeloureterostomy using the native ureter. The postoperative course was uneventful and the patient was discharged on the third postoperative day. DISCUSSION: Robotic-assisted pyelo-ureterostomy appears as a safe and efficient technique for management of complicated urological complications postrenal transplantation using the native ureter. Intrapelvic ICG injection, not possible with open surgery, helps identifying the grafted pelvis thus reducing operative time and avoiding unnecessary dissection of the vascular hilum of the graft. Because of minimal dissection and the short operative time, abdominal drainage is unnecessary and the postoperative course is usually uneventful with a fast discharge from the hospital.

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.