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Puri P, Friedmacher F, Farrugia MK, Sharma S, Esposito C, Mattoo TK. Primary vesicoureteral reflux. Nat Rev Dis Primers 2024; 10:75. [PMID: 39389958 DOI: 10.1038/s41572-024-00560-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/12/2024] [Indexed: 10/12/2024]
Abstract
Primary vesicoureteral reflux (VUR) is one of the most common urological abnormalities in infants and children. The association of VUR, urinary tract infection (UTI) and renal parenchymal damage is well established. The most serious complications of VUR-associated reflux nephropathy are hypertension and proteinuria with chronic kidney disease. Over the past two decades, our understanding of the natural history of VUR has improved, which has helped to identify patients at increased risk of both VUR and VUR-associated renal injury. The main goals in the treatment of paediatric patients with VUR are the prevention of recurrent UTIs and minimizing the risk of renal scarring and long-term renal impairment. Currently, there are four options for managing primary VUR in infants and children: surveillance or intermittent treatment of UTIs with management of bladder and bowel dysfunction; continuous antibiotic prophylaxis; endoscopic subureteral injection of tissue-augmenting substances; and ureteral reimplantation via open, laparoscopic or robotic-assisted surgery. Current debates regarding key aspects of management include when to perform diagnostic imaging and how to best identify the paediatric patients that will benefit from continuous antibiotic prophylaxis or surgical intervention, including endoscopic injection therapy and minimally invasive ureteral reimplantation. Evolving technologies, such as artificial intelligence, have the potential to assist clinicians in the decision-making process and in the individualization of diagnostic imaging and treatment of infants and children with VUR in the future.
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Affiliation(s)
- Prem Puri
- University College Dublin, Dublin, Ireland.
| | - Florian Friedmacher
- Department of Paediatric Surgery and Paediatric Urology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany
| | - Marie-Klaire Farrugia
- Department of Paediatric Urology, Chelsea and Westminster Hospital (West London Children's Healthcare), London, UK
- Imperial College, London, UK
| | - Shilpa Sharma
- Department of Paediatric Surgery, All India Institute of Medical Sciences, New Delhi, India
| | - Ciro Esposito
- Division of Paediatric Surgery, Federico II University Hospital, Naples, Italy
| | - Tej K Mattoo
- Departments of Paediatrics (Nephrology) and Urology, Wayne State University School of Medicine, Detroit, MI, USA
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Prakash P, Verma S, Gupta S. Influence of microbiome in intraprostatic inflammation and prostate cancer. Prostate 2024; 84:1179-1188. [PMID: 38899408 DOI: 10.1002/pros.24756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Revised: 05/22/2024] [Accepted: 06/10/2024] [Indexed: 06/21/2024]
Abstract
BACKGROUND Chronic infection and inflammation have been linked to the development of prostate cancer. Dysbiosis of the oral and gut microbiomes and subsequent microbial translocation can lead to pathogenic prostate infections. Microbial-produced metabolites have also been associated with signaling pathways that promote prostate cancer development. A comprehensive discussion on the mechanisms of microbiome infection and the prostate microenvironment is essential to understand prostate carcinogenesis. METHODS Published studies were used from the National Center for Biotechnology Information (NCBI) database to conduct a narrative review. No restrictions were applied in the selection of articles. RESULTS Microbiome-derived short-chain fatty acids (SCFAs) have been found to upregulate multiple signaling pathways, including MAPK and PI3K, through IGF-1 signaling and M2 macrophage polarization. SCFAs can also upregulate Toll-like receptors, leading to chronic inflammation and the creation of a pro-prostate cancer environment. Dysbiosis of oral microbiota has been correlated with prostate infection and inflammation. Additionally, pathogenic microbiomes associated with urinary tract infections have shown a link to prostate cancer, with vesicoureteral reflux potentially contributing to prostate infection. CONCLUSIONS This review offers a comprehensive understanding of the impact of microbial infections linked to intraprostatic inflammation as a causative factor for prostate cancer. Further studies involving the manipulation of the microbiome and its produced metabolites may provide a more complete understanding of the microenvironmental mechanisms that promote prostate carcinogenesis.
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Affiliation(s)
- Pranav Prakash
- College of Arts and Sciences, Case Western Reserve University, Cleveland, Ohio, USA
- Department of Urology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
| | - Shiv Verma
- Department of Urology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
- The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
| | - Sanjay Gupta
- Department of Urology, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
- The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
- Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA
- Department of Nutrition, Case Western Reserve University, Cleveland, Ohio, USA
- Division of General Medical Sciences, Case Comprehensive Cancer Center, Cleveland, Ohio, USA
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Colceriu MC, Aldea PL, Bulată B, Delean D, Sevastre-Berghian A, Clichici S, Boț (Răchişan) AL, Mocan T. Nadir Creatinine in Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): A Single-Center Experience. CHILDREN (BASEL, SWITZERLAND) 2024; 11:928. [PMID: 39201862 PMCID: PMC11352228 DOI: 10.3390/children11080928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 07/28/2024] [Accepted: 07/30/2024] [Indexed: 09/03/2024]
Abstract
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.
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Affiliation(s)
- Marius-Cosmin Colceriu
- Discipline of Physiology, Department of Functional Biosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.S.-B.); (S.C.); (T.M.)
- Second Pediatric Discipline, Department of Mother and Child, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400177 Cluj-Napoca, Romania;
| | - Paul Luchian Aldea
- Discipline of Public Health and Management, Department of Community Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Bogdan Bulată
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (B.B.); (D.D.)
| | - Dan Delean
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (B.B.); (D.D.)
| | - Alexandra Sevastre-Berghian
- Discipline of Physiology, Department of Functional Biosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.S.-B.); (S.C.); (T.M.)
| | - Simona Clichici
- Discipline of Physiology, Department of Functional Biosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.S.-B.); (S.C.); (T.M.)
| | - Andreea-Liana Boț (Răchişan)
- Second Pediatric Discipline, Department of Mother and Child, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400177 Cluj-Napoca, Romania;
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (B.B.); (D.D.)
| | - Teodora Mocan
- Discipline of Physiology, Department of Functional Biosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (A.S.-B.); (S.C.); (T.M.)
- Nanomedicine Department, Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania
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Cai PY, Kurtz MP, Nelson CP. Urology Mythbusters: Does prevalence of vesicoureteral reflux in children vary by race? J Pediatr Urol 2024; 20:514-518. [PMID: 38383275 DOI: 10.1016/j.jpurol.2024.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 02/05/2024] [Indexed: 02/23/2024]
Abstract
In this edition of Mythbusters, we examine the premise that prevalence of vesicoureteral reflux (VUR) in children varies by race. Specifically, we consider whether there is evidence supporting the contention that VUR is more common in White children and less common in Black children. Statements regarding the lower prevalence of VUR in Black children are ubiquitous in both research papers and reviews. Many of the references cited in support of these statements do not actually support the existence of racial variation in VUR, due to uncontrolled single-arm study designs, highly selected samples at risk for bias, or simply not addressing VUR prevalence at all. There is a small group of studies which directly compared VUR prevalence among children undergoing cystography, and these studies have found VUR to be less common among Black children compared to White children. However, the results of such papers can only be considered in the context of a system in which systemic bias and racism may impact access and care delivery in profound ways. Given that race is a social construct that bears little relationship to shared genetic ancestry or underlying biological characteristics, these findings must be approached with extreme caution. The goals of pediatric urological care should be to confer equitable care to all young children regardless of race.
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Affiliation(s)
- Peter Y Cai
- Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Michael P Kurtz
- Boston Children's Hospital and Harvard Medical School, Boston, MA, USA
| | - Caleb P Nelson
- Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
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Saraga M, Saraga-Babić M, Arapović A, Vukojević K, Pogorelić Z, Simičić Majce A. The Intrarenal Reflux Diagnosed by Contrast-Enhanced Voiding Urosonography (ceVUS): A Reason for the Reclassification of Vesicoureteral Reflux and New Therapeutic Approach? Biomedicines 2024; 12:1015. [PMID: 38790977 PMCID: PMC11117776 DOI: 10.3390/biomedicines12051015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 04/30/2024] [Accepted: 05/02/2024] [Indexed: 05/26/2024] Open
Abstract
Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result in reflux nephropathy when accompanied by urinary tract infection (UTI). The prevalence of IRR in patients with diagnosed VUR is 1-11% when using voiding cystourethrography (VCUG), while 11.9-61% when applying the contrast-enhanced voiding urosonography (ceVUS). The presence of IRR diagnosed by VCUG often correlates with parenchymal scars, when diagnosed by a 99mTc dimercaptosuccinic acid scan (DMSA scan), mostly in kidneys with high-grade VURs, and when diagnosed by ceVUS, it correlates with the wide spectrum of parenchymal changes on DMSA scan. The study performed by both ceVUS and DMSA scans showed IRRs associated with non-dilated VURs in 21% of all detected VURs. A significant difference regarding the existence of parenchymal damage was disclosed between the IRR-associated and IRR-non-associated VURs. A higher portion of parenchymal changes existed in the IRR-associated VURs, regardless of the VUR grade. That means that kidneys with IRR-associated VURs represent the high-risk group of VURs, which must be considered in the future classification of VURs. When using ceVUS, 62% of places where IRR was found were still unaffected by parenchymal changes. That was the basis for our recommendation of preventive use of long-term antibiotic prophylaxis until the IRR disappearance, regardless of the VUR grade. We propose a new classification of VURs using the ceVUS method, in which each VUR grade is subdivided based on the presence of an IRR.
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Affiliation(s)
- Marijan Saraga
- School of Medicine, University of Split, 21000 Split, Croatia; (Z.P.)
| | - Mirna Saraga-Babić
- Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia;
| | - Adela Arapović
- Department of Pediatric, University Hospital of Split, 21000 Split, Croatia; (A.A.); (A.S.M.)
| | - Katarina Vukojević
- Department of Anatomy, Histology and Embryology, School of Medicine, University of Split, 21000 Split, Croatia;
| | - Zenon Pogorelić
- School of Medicine, University of Split, 21000 Split, Croatia; (Z.P.)
- Department of Pediatric Surgery, University Hospital of Split, 21000 Split, Croatia
| | - Ana Simičić Majce
- Department of Pediatric, University Hospital of Split, 21000 Split, Croatia; (A.A.); (A.S.M.)
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Kabir S, Pippi Salle JL, Chowdhury MEH, Abbas TO. Quantification of vesicoureteral reflux using machine learning. J Pediatr Urol 2024; 20:257-264. [PMID: 37980211 DOI: 10.1016/j.jpurol.2023.10.030] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 10/17/2023] [Accepted: 10/21/2023] [Indexed: 11/20/2023]
Abstract
INTRODUCTION The radiographic grading of voiding cystourethrogram (VCUG) images is often used to determine the clinical course and appropriate treatment in patients with vesicoureteral reflux (VUR). However, image-based evaluation of VUR remains highly subjective, so we developed a supervised machine learning model to automatically and objectively grade VCUG data. STUDY DESIGN A total of 113 VCUG images were gathered from public sources to compile the dataset for this study. For each image, VUR severity was graded by four pediatric radiologists and three pediatric urologists (low severity scored 1-3; high severity 4-5). Ground truth for each image was assigned based on the grade diagnosed by a majority of the expert assessors. Nine features were extracted from each VCUG image, then six machine learning models were trained, validated, and tested using 'leave-one-out' cross-validation. All features were compared and contrasted, with the highest-ranked then being used to train the final models. RESULTS F1-score is a metric that is often used to indicate performance accuracy of machine learning models. When using the highest-ranked VCUG image features, F1-scores for the support vector machine (SVM) and multi-layer perceptron (MLP) classifiers were 90.27 % and 91.14 %, respectively, indicating a high level of accuracy. When using all features combined, F1 scores were 89.37 % for SVM and 90.27 % for MLP. DISCUSSION These findings indicate that a distorted pattern of renal calyces is an accurate predictor of high-grade VUR. Machine learning protocols can be enhanced in future to improve objective grading of VUR.
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Affiliation(s)
- Saidul Kabir
- Department of Electrical and Electronic Engineering, University of Dhaka, Dhaka, 1000, Bangladesh
| | | | | | - Tariq O Abbas
- Urology Division, Surgery Department, Sidra Medicine, Qatar.
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Quiring ME, Son Y, Thaker R, Davidson N, Wu E, Fink BA, Thomas B, Gentry NB, Yossef A, DeMario VK, Earnshaw L, Weldekidan B, Dean G. Vesicoureteral reflux severity is not associated with unplanned urinary catheterization or length of hospital stay after ureteroneocystostomy. J Pediatr Urol 2024; 20:183-190. [PMID: 37770341 DOI: 10.1016/j.jpurol.2023.08.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Revised: 08/10/2023] [Accepted: 08/31/2023] [Indexed: 09/30/2023]
Abstract
INTRODUCTION Vesicoureteral reflux (VUR) is a common urologic condition affecting approximately 1% of all children. Surgical success often depends on the grade of VUR, as patients with grades 4 or 5 have been have a greater risk for postoperative complications. Unplanned urinary catheter placement (UCP) postoperatively and prolonged length of hospital stay (LOS) are indicative of unexpected complications. The association between VUR severity and such metrics remain unclear. OBJECTIVE The study's objective is to determine if the severity of VUR is associated with higher rates of UCP or prolonged LOS after ureteroneocystostomy (UNC). STUDY DESIGN The 2020 National Surgical Quality Improvement Program Pediatric database was analyzed for patients with VUR. A total of 1742 patients were initially evaluated with 1373 meeting exclusion criteria. The patients were divided into 3 groups of varying voiding cystourethrogram (VCUG) or radionuclide cystogram (RNC) severity: VCUG Grade 1 or RNC Grade 1 (Group A), VCUG Grade 2 or 3 or RNC Grade 2 (Group B), and VCUG Grade 4 or 5 or RNC Grade 3 (Group C). Basic statistical analysis was performed, and logistic regression was performed with both UCP and LOS as dependent variables. RESULTS Among the 1373 patients, 2.9% were included in Group A, 32.5% were in Group B, and 64.6% were in Group C. Significant differences were found among the groups for mean age, gender, inpatient status, rate of congenital malformation, ureteral stents, and ASA classification. Regarding surgical treatment, differences were also found comparing mean operative time, LOS, laterality and type of procedure, urine culture results, rates of UTI, surgical site infections, postoperative returns to the emergency department, and unplanned procedures and catheterization. Multivariate analysis demonstrated no significant association between the rate of UCP and VUR severity, while postoperative UTI and unplanned procedure were both independent factors associated with UCP postoperatively. Additionally, postoperative UTI, ASA classification, mean operation time, ureteral stent placement, unplanned procedure, and UCP were independent factors found to contribute to LOS. CONCLUSION Greater VUR severity does not appear to increase the need for catheterization or prolong hospital stay, while the development of a UTI postoperatively or having an additional unplanned procedure are associated with an increased likelihood of both. The postoperative course after UNC also appears to be influenced more so by other factors such as the operative approach and whether complications arise.
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Affiliation(s)
- Mark E Quiring
- University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX 76107, USA.
| | - Young Son
- Jefferson Health New Jersey, Department of Urology, 18 E Laurel Rd, Stratford, NJ 08084, USA.
| | - Ranel Thaker
- Lake Erie College of Osteopathic Medicine, 1858 W Grandview Blvd, Erie, PA 16509, USA.
| | - Noah Davidson
- Lake Erie College of Osteopathic Medicine, 1858 W Grandview Blvd, Erie, PA 16509, USA.
| | - Edward Wu
- Alabama College of Osteopathic Medicine, 445 Health Sciences Blvd, Dothan, AL 36303, USA.
| | - Benjamin A Fink
- Jefferson Health New Jersey, Department of Urology, 18 E Laurel Rd, Stratford, NJ 08084, USA; Rowan University, School of Osteopathic Medicine, 113 E Laurel Rd, Stratford, NJ 08084, USA.
| | - Brian Thomas
- Rowan University, School of Osteopathic Medicine, 113 E Laurel Rd, Stratford, NJ 08084, USA.
| | - Nathaniel B Gentry
- New York Institute of Technology College of Osteopathic Medicine, 2405 Aggie Rd, Jonesboro, AR 72401, USA.
| | - Angie Yossef
- Pacific Northwest University of Health Sciences College of Osteopathic Medicine, 200 University Parkway, Yakima, WA 98901, USA.
| | - Virgil K DeMario
- University of the Incarnate Word, School of Osteopathic Medicine, 7615 Kennedy Hill Dr, San Antonio, TX 78235, USA.
| | - Lance Earnshaw
- Jefferson Health New Jersey, Department of Urology, 18 E Laurel Rd, Stratford, NJ 08084, USA.
| | - Blen Weldekidan
- Nationwide Children's Hospital, 700 Children's Dr, Columbus, OH 43205, USA.
| | - Gregory Dean
- Temple University, Department of Urology, 3401 N Broad St, Philadelphia, PA 19140, USA.
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Colceriu MC, Aldea PL, Boț (Răchişan) AL, Bulată B, Delean D, Grama A, Mititelu A, Decea RM, Sevastre-Berghian A, Clichici S, Pop TL, Mocan T. The Utility of Noninvasive Urinary Biomarkers for the Evaluation of Vesicoureteral Reflux in Children. Int J Mol Sci 2023; 24:17579. [PMID: 38139407 PMCID: PMC10743802 DOI: 10.3390/ijms242417579] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/10/2023] [Accepted: 12/15/2023] [Indexed: 12/24/2023] Open
Abstract
Vesicoureteral reflux (VUR) is one of the most important disorders encountered in pediatric nephrology due to its frequency and potential evolution to chronic kidney disease (CKD). The aim of our study was to identify noninvasive and easy-to-determine urinary markers to facilitate the diagnosis and staging of VUR. We performed a cross-section study including 39 patients with VUR followed over three years (August 2021-September 2023) and 39 children without urinary disorder (the control group). We measured the urinary concentration of interleukin-6 (IL-6), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in VUR and healthy controls. Moreover, we analyzed the correlation between these biomarkers and the presence of renal scars (RS), reflux nephropathy (RN), and CKD. The NGAL concentrations were significantly higher in patients with VUR than in the controls (p = 0.02). Regarding the severity of the reflux, NGAL/creatinine and LL-37/creatinine were positively correlated with severe reflux (p = 0.04, respectively, p = 0.02). In patients with VUR and RS, LL-37/creatinine was significantly lower (p = 0.01). LL-37/creatinine with an AUC of 0.71 and NGAL/creatinine with an AUC of 0.72 could be acceptable diagnostic tests for severe VUR. In conclusion, urinary IL-6, NGAL, and LL-37 could serve as valuable markers for diagnosing and predicting outcomes in patients with VUR and RN.
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Affiliation(s)
- Marius-Cosmin Colceriu
- Discipline of Physiology, Department of Functional Biosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (R.M.D.); (A.S.-B.); (S.C.); (T.M.)
- Second Pediatric Discipline, Department of Mother and Child, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400177 Cluj-Napoca, Romania (A.G.); (A.M.); (T.L.P.)
| | - Paul Luchian Aldea
- Discipline of Public Health and Management, Department of Community Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania;
| | - Andreea-Liana Boț (Răchişan)
- Second Pediatric Discipline, Department of Mother and Child, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400177 Cluj-Napoca, Romania (A.G.); (A.M.); (T.L.P.)
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (B.B.)
| | - Bogdan Bulată
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (B.B.)
| | - Dan Delean
- Pediatric Nephrology, Dialysis and Toxicology Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania; (B.B.)
| | - Alina Grama
- Second Pediatric Discipline, Department of Mother and Child, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400177 Cluj-Napoca, Romania (A.G.); (A.M.); (T.L.P.)
- Second Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Alexandra Mititelu
- Second Pediatric Discipline, Department of Mother and Child, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400177 Cluj-Napoca, Romania (A.G.); (A.M.); (T.L.P.)
| | - Roxana Maria Decea
- Discipline of Physiology, Department of Functional Biosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (R.M.D.); (A.S.-B.); (S.C.); (T.M.)
| | - Alexandra Sevastre-Berghian
- Discipline of Physiology, Department of Functional Biosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (R.M.D.); (A.S.-B.); (S.C.); (T.M.)
| | - Simona Clichici
- Discipline of Physiology, Department of Functional Biosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (R.M.D.); (A.S.-B.); (S.C.); (T.M.)
| | - Tudor Lucian Pop
- Second Pediatric Discipline, Department of Mother and Child, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400177 Cluj-Napoca, Romania (A.G.); (A.M.); (T.L.P.)
- Second Pediatric Clinic, Emergency Clinical Hospital for Children, 400177 Cluj-Napoca, Romania
| | - Teodora Mocan
- Discipline of Physiology, Department of Functional Biosciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania; (R.M.D.); (A.S.-B.); (S.C.); (T.M.)
- Nanomedicine Department, Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania
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Parry CM, Taylor A, Williams R, Lally H, Corbett HJ. Antimicrobial resistance of breakthrough urinary tract infections in young children receiving continual antibiotic prophylaxis. Eur J Pediatr 2023; 182:4087-4093. [PMID: 37401978 DOI: 10.1007/s00431-023-05087-w] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 06/21/2023] [Accepted: 06/24/2023] [Indexed: 07/05/2023]
Abstract
Continual antibiotic prophylaxis (CAP) can reduce the risk of recurrent UTI (rUTI). However, antimicrobial resistance in subsequent UTIs is a concern. This study aimed to explore antimicrobial resistance in young children prescribed CAP for rUTIs. A retrospective review of patient records/microbiology results was undertaken for children < 2 years of age, on CAP, with 2-3 clean catch/mid-stream/supra-pubic aspirate urine cultures with a pure growth of bacteria, between January 2017 and December 2019. One hundred twenty-four urine specimens from 54 patients (26 (48%) males, median age 6 months) were analysed. CAP prescribed was trimethoprim in 37 (69%), cefalexin in 11 (29%), and nitrofurantoin in 6 (11%). Based on antimicrobial susceptibility of the index UTI within the study period, 41 patients (76%) grew organisms on urine culture classified as sensitive and 13 (24%) resistant. Thirty-five (65%) children had congenital anomaly of the kidneys and urinary tract (CAKUT); they were more likely to be in the resistant group (P = 0.032). Escherichia coli (37/54, 69%) was the commonest index uropathogen. The resistant group had a higher proportion of non-E. coli index UTI pathogens (P = 0.098). Breakthrough UTI with a CAP-resistant organism was more likely in the resistant group (P = 0.010). Age, sex, and kidney scarring on DMSA (dimercaptosuccinic acid) scan were not significantly different between groups. Conclusion: Over a 3-year period, the proportion of children on CAP with resistant organism UTI doubled and resistant infections were more likely in children with CAKUT. Development of non-antimicrobial prophylaxis options is required. What is Known: • Recurrent urinary tract infections are common in children, particularly in those with underlying anatomical abnormalities of the kidneys and urinary tract. • Continuous antibiotic prophylaxis is used frequently in these children, however there is a lack of consensus on whether the potential benefits of CAP outweigh the harms. What is New: • This study adds further evidence towards the consequences of using continuous antibiotic prophylaxis in recurrent UTI; specifically, a 2-fold increase in antimicrobial resistance was seen in subsequent UTIs following long-term use of CAP, providing further vigour for the need for non-antibiotic alternatives.
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Affiliation(s)
- Christopher M Parry
- NIHR Alder Hey Clinical Research Facility, East Prescot Road, Liverpool, UK.
- Department of Women's and Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
| | - Andrew Taylor
- Department of Pharmacy, Alder Hey Children's Hospital, Liverpool, UK
| | - Ruby Williams
- Department of Paediatric Surgery, Alder Hey Children's Hospital, Liverpool, UK
| | - Hayley Lally
- Department of Paediatric Surgery, Alder Hey Children's Hospital, Liverpool, UK
| | - Harriet J Corbett
- Department of Paediatric Surgery, Alder Hey Children's Hospital, Liverpool, UK
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10
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Oguz F, Yildiz T, Gecit I, Gungor H, Ciftci H, Aksoy Y, Yagmur I. Efficacy and safety of Hyadex for treatment of vesicoureteral reflux: a multicenter experience. J Int Med Res 2023; 51:3000605231195165. [PMID: 37646623 PMCID: PMC10469260 DOI: 10.1177/03000605231195165] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 07/31/2023] [Indexed: 09/01/2023] Open
Abstract
OBJECTIVE This study was performed to evaluate the efficacy and safety of dextranomer/cross-linked hyaluronic acid (Hyadex) in patients with a clinical diagnosis of vesicoureteral reflux (VUR). METHODS In this cross-sectional multicenter observational study, Hyadex was used in four different centers for the endoscopic treatment of VUR from 2020 to 2022. The study involved 74 patients (93 renal units) who were diagnosed with VUR according to voiding cystourethrography (VCUG) findings and were considered suitable for subureteric endoscopic treatment. The follow-up time (control VCUG time) was 3 months. RESULTS In the VCUG evaluation, grade I VUR was found in 13 renal units, grade II in 23 renal units, grade III in 42 renal units, and grade IV in 12 renal units. The success rates of Hyadex treatment according to the degree of VUR were as follows: 84.6% for grade I, 82.6% for grade II, 71.4% for grade III, and 66.0% for grade IV. No major complications were observed. CONCLUSION Endoscopic subureteric Hyadex injection had high success rates in appropriately selected patients with VUR and may be used as the first-line treatment for children with VUR.
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Affiliation(s)
- Fatih Oguz
- Department of Urology, Inonu University Faculty of Medicine, Malatya, Türkiye
| | - Turan Yildiz
- Department of Pediatric Surgery, Inonu University Faculty of Medicine, Malatya, Türkiye
| | - Ilhan Gecit
- Department of Urology, Inonu University Faculty of Medicine, Malatya, Türkiye
| | - Hasan Gungor
- Department of Urology, Inonu University Faculty of Medicine, Malatya, Türkiye
| | - Halil Ciftci
- Department of Urology, Faculty of Medicine, Harran University, Malatya, Türkiye
| | - Yılmaz Aksoy
- Department of Urology, Atatürk University Faculty of Medicine, Malatya, Türkiye
| | - Ismail Yagmur
- Department of Urology, Faculty of Medicine, Harran University, Malatya, Türkiye
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11
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Ansari MS, Banthia R, Jain S, Kaushik VN, Danish N, Yadav P. Long term outcomes of Cohen's cross trigonal reimplantation for primary vesicoureteral reflux in poorly functioning kidney. World J Clin Cases 2023; 11:3750-3755. [PMID: 37383119 PMCID: PMC10294151 DOI: 10.12998/wjcc.v11.i16.3750] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/19/2023] [Accepted: 05/06/2023] [Indexed: 06/02/2023] Open
Abstract
BACKGROUND Open ureteric reimplantation by cross trigonal technique described by Cohen is considered a common surgical option for correction of vesicoureteral reflux (VUR). There is a lack of evidence in literature though for what happens to such kidneys, in the long run, particularly those which are poorly functioning. AIM To assess the long-term outcomes of ureteric reimplantation in poorly functioning kidneys in children with unilateral primary VUR. METHODS Children with unilateral primary VUR and a relative renal function of less than 35% who underwent open or laparoscopic ureteric reimplantation between January 2005 and January 2017 were included in the study. Patients who had a follow up of less than five years were excluded. Preoperative evaluation consisted of a voiding cystourethrogram and Dimercaptosuccinic acid (DMSA) scan. In the follow-up period, patients underwent a diuretic scan at 6 weeks and 6 months. Follow up ultrasound was done for change in grade of hydronephrosis and retrovesical ureteric diameter. Subsequent follow up was done at 6 monthly intervals with evaluation for proteinuria and hypertension and any recurrent urinary tract infection (UTI). For assessment of cortical function, DMSA was repeated annually for 5 years after surgery. A paired-samples t-test was used to test the mean difference of DMSA between pre-post observations. RESULTS During this period, 36 children underwent ureteric reimplantation for unilateral primary VUR. After excluding those with insufficient follow-up, 31 were included in the analysis. Most of the patients were males (n = 26/31, 83.8%). Patient's age (mean ± SD, range) was 5.21 ± 3.71, 1-18 years. The grades of VUR were grade II (1 patient), grade III (8 patients), grade IV (10 patients), and grade V (12 patients). The pre and postoperative DMSA was 24.064 ± 12.02 and 24.06 ± 10.93, which was almost the same (statistically equal, paired-samples t-test: P = 0.873). The median (range) follow-up duration was 82 (60-120) mo. One patient had persistent reflux after surgery (preoperative: grade IV, postoperative: grade III), and the very same patient developed recurrent UTI. The difference in the preoperative and postoperative DRF was less than 10% in 29 patients. In one patient, the DRF decreased by 17% (22% to 05%) while in another patient, the DRF increased by 12% (25% to 37%) after surgery. None of the patients had an increase in scarring after surgery. 15% of patients were hypertensive before surgery and all of them continued to be hypertensive after surgery while none developed hypertension after surgery. None of the patients had significant proteinuria (> 150 mg/d) during the follow-up period. CONCLUSION Children with unilateral primary VUR and poorly functioning kidney maintain the renal function over the long term in most cases. Hypertension and proteinuria do not progress over time in these patients.
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Affiliation(s)
- Mohd Sualeh Ansari
- Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Ravi Banthia
- Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Shrey Jain
- Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Vinay N Kaushik
- Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Nayab Danish
- Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
| | - Priyank Yadav
- Department of Urology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India
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Colceriu MC, Aldea PL, Răchișan AL, Clichici S, Sevastre-Berghian A, Mocan T. Vesicoureteral Reflux and Innate Immune System: Physiology, Physiopathology, and Clinical Aspects. J Clin Med 2023; 12:jcm12062380. [PMID: 36983379 PMCID: PMC10058356 DOI: 10.3390/jcm12062380] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/13/2023] [Accepted: 03/17/2023] [Indexed: 03/30/2023] Open
Abstract
Vesicoureteral reflux represents one of the most concerning topics in pediatric nephrology due to its frequency, clinical expression with the potential to evolve into chronic kidney disease, and last but not least, its socio-economic implications. The presence of vesicoureteral reflux, the occurrence of urinary tract infections, and the development of reflux nephropathy, hypertension, chronic kidney disease, and finally, end-stage renal disease represent a progressive spectrum of a single physiopathological condition. For the proper management of these patients with the best clinical outcomes, and in an attempt to prevent the spread of uropathogens' resistance to antibacterial therapy, we must better understand the physiopathology of urinary tract infections in patients with vesicoureteral reflux, and at the same time, we should acknowledge the implication and response of the innate immune system in this progressive pathological condition. The present paper focuses on theoretical aspects regarding the physiopathology of vesicoureteral reflux and the interconditionality between urinary tract infections and the innate immune system. In addition, we detailed aspects regarding cytokines, interleukins, antimicrobial peptides, and proteins involved in the innate immune response as well as their implications in the physiopathology of reflux nephropathy. New directions of study should focus on using these innate immune system effectors as diagnostic and therapeutic tools in renal pathology.
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Affiliation(s)
- Marius-Cosmin Colceriu
- Department of Functional Biosciences, Discipline of Physiology, Iuliu Haţieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Paul Luchian Aldea
- Department of Community Medicine, Discipline of Public Health and Management, Iuliu Haţieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Andreea-Liana Răchișan
- Department of Mother and Child, Discipline of Pediatrics II, Iuliu Haţieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Simona Clichici
- Department of Functional Biosciences, Discipline of Physiology, Iuliu Haţieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Alexandra Sevastre-Berghian
- Department of Functional Biosciences, Discipline of Physiology, Iuliu Haţieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
| | - Teodora Mocan
- Department of Functional Biosciences, Discipline of Physiology, Iuliu Haţieganu University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
- Nanomedicine Department, Regional Institute of Gastroenterology and Hepatology, 400158 Cluj-Napoca, Romania
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13
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Nishi M, Eura R, Hayashi C, Gohbara A, Yamazaki Y. Vesicoscopic ureteral reimplantation with a modified Glenn-Anderson technique for vesicoureteral reflux. J Pediatr Urol 2023:S1477-5131(23)00068-2. [PMID: 36959038 DOI: 10.1016/j.jpurol.2023.02.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 12/19/2022] [Accepted: 02/22/2023] [Indexed: 02/27/2023]
Abstract
INTRODUCTION Vesicoureteral reflux (VUR), commonly referred to as urinary reflux, is one of the most common congenital urological anomaly to occur during childhood. Historically, open vesicoureteral reimplantation has been the gold standard in the surgical treatment of VUR. Currently, vesicoscopic ureteral reimplantation is used as a minimally invasive alternative to open ureteral reimplantation. Most vesicoscopic procedures are performed using the transtrigonal Cohen technique. As a non-transtrigonal technique, the vesicoscopic Politano-Leadbetter technique is also performed, but requires dissection outside the bladder under a narrow surgical field, and in boy carries a risk of vas deferens injury. OBJECTIVE This study evaluated surgical outcomes and perioperative findings for vesicoscopic ureteral reimplantation using a modified Glenn-Anderson technique in children with VUR. STUDY DESIGN Eighteen consecutive children who underwent vesicoureteral ureteral reimplantation using a modified Glenn-Anderson technique were included in this study. The surgical procedure was explained and surgical outcomes and perioperative findings were evaluated. RESULTS Patients comprised 9 boys and 9 girls with 29 cases of ureteral reflux (7 unilateral cases, 11 bilateral cases). All procedures were performed laparoscopically, with no cases requiring conversion to open surgery. Median operative time was 143 min for unilateral VUR and 194 min for bilateral VUR. Only one case showed a complication (Clavien-Dindo grade 1). The remaining 17 cases showed no complications, with removal of the urethral catheter and discharge 2 days postoperatively. Seventeen of the 18 cases underwent postoperative voiding cystourethrography, showing no VUR in all cases. DISCUSSION Vesicoscopic ureteral reimplantation is a minimally invasive alternative to open surgery, with most procedures performed using a transtrigonal Cohen technique. Regardless of whether the surgery is open or laparoscopic, a disadvantage of the Cohen technique is that postoperative transureteral treatment may not be possible. The Politano-Leadbetter technique has been reported as a non-transtrigonal technique. However, this requires dissection outside the bladder under a narrow surgical field, and carries a risk of vas deferens injury in boys. In this study, vesicoscopic ureteral reimplantation using a modified Glenn-Anderson technique provided good surgical outcomes with minimal perioperative complications and easy manipulation under a wide field of view. CONCLUSION Although many minimally invasive treatments are available, vesicoscopic ureteral reimplantation using a modified Glenn-Anderson technique is safe and effective for patients with VUR 4 years old. To demonstrate the further utility of this procedure, long-term outcomes and safety evaluations are needed in a larger number of cases.
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Affiliation(s)
- Morihiro Nishi
- Department of Urology, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa, Minami-ku, Yokohama 232-8555, Japan.
| | - Rumiko Eura
- Department of Urology, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa, Minami-ku, Yokohama 232-8555, Japan
| | - Chihiro Hayashi
- Department of Urology, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa, Minami-ku, Yokohama 232-8555, Japan
| | - Ayako Gohbara
- Department of Urology, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa, Minami-ku, Yokohama 232-8555, Japan
| | - Yuichiro Yamazaki
- Department of Urology, Kanagawa Children's Medical Center, 2-138-4 Mutsukawa, Minami-ku, Yokohama 232-8555, Japan
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14
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Evaluation of renal oxygenation by near-infrared spectroscopy during endoscopic injection of bulking agents in children with vesicoureteral reflux. Pediatr Surg Int 2023; 39:116. [PMID: 36773203 DOI: 10.1007/s00383-023-05407-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/31/2023] [Indexed: 02/12/2023]
Abstract
BACKGROUND Near infrared spectroscopy (NIRS) is the measuring of regional tissue oxygenation (rSO2) by interpreting oxyhemoglobin and deoxyhemoglobin signals that come back by transmitting near infrared light to tissues. The effect of endourological interventions on renal perfusion in children is largely unknown. AIMS To evaluate the effects of endoscopic injection of bulking agents (EIBA) for vesicoureteral reflux (VUR) on renal oxygenation (RO) using renal NIRS monitoring, which shows renal perfusion and oxygenation changes. STUDY DESIGN Case-control study. METHODS Group I had bilateral inguinal surgery, Group II cystoscopy, and Group III, EIBA for VUR with 30 patients in each group. During the operation, vital signs, peripheral oxygen saturation, end-tidal carbon dioxide, and renal regional oxygen saturation index (rSO2) values by bilateral renal NIRS monitoring were recorded. NIRS values before induction (T0) to postoperative (Tend) were determined. A 20% or more reduction in renal rSO2 (%20↓rSO2) was considered significant. Group III was also evaluated as subgroup III-A (not having "%20↓rSO2") and subgroup III-B ("%20↓rSO2"). RESULTS The rSO2 decrease was observed in the first 5 min for both sides in group III. The most significant drop was at T30 for the right kidney and a significant decrease in rSO2, 20% or more, was observed in 6 renal units of 4 patients having higher SFU grading and renal scar in group III. CONCLUSION EIBA may transitionally impair renal oxygenation. Higher SFU grading and renal scar may increase the risk of renal hypoxia during EIBA.
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15
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CAKUT: A Pediatric and Evolutionary Perspective on the Leading Cause of CKD in Childhood. Pediatr Rep 2023; 15:143-153. [PMID: 36810342 PMCID: PMC9944871 DOI: 10.3390/pediatric15010012] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 02/05/2023] [Accepted: 02/07/2023] [Indexed: 02/12/2023] Open
Abstract
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.
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16
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Zadeh NE, Sadeghi-Bojd S, Ansari-Moghaddam A, Mashhadi A, Zadehmir M. Color Doppler Ultrasound's Utility in Detecting Vesicoureteral Reflux Using the Ureteral Jet Angle. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2023; 42:723-728. [PMID: 36190168 DOI: 10.1002/jum.16107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/05/2022] [Revised: 09/04/2022] [Accepted: 09/11/2022] [Indexed: 06/16/2023]
Abstract
OBJECTIVES This study hypothesizes using color Doppler ultrasound to measure ureteral jet angles (UJA) as a diagnostic screening tool for reflux. METHODS The present prospective cohort study included 122 patients and 238 renal unit pediatric patients suspected of VUR who presented to our hospital between 2019 and 2021. All patients underwent ultrasonography and VCUG, and the UJA was measured color Doppler evaluation of the ureteral jet. The UJA was compared with the VCUG findings in patients with and without reflux. SPSS 26 was used to analyze the data. RESULTS A total of 96 patients and 139 renal units exhibited reflux. The mean ureteral jet angle in refluxing units was 60.47 + 16.66 degrees, whereas, it was 42.59 + 13.26 degrees in non-refluxing units, a significant difference between the two groups (P < .001). The mean ureteral jet angle was 42.59, 45.89, 60.32, 68.23, and 56.16, for reflux grading from 0 to 5 (except grade 1), respectively. The angle value in each reflux grade increased significantly except for grade 5. For reflux detection (grade I-V), a cut-off angle of 50 degrees was associated with sensitivity and specificity of 70 and 79, respectively. Grade IV/V reflux can be diagnosed with a sensitivity of 70% and specificity of 84% using a cut-off angle of 68 degrees or greater. CONCLUSIONS UJA detection via color Doppler ultrasound demonstrates high accuracy, is non-invasive method can be utilized as an alternative primary diagnostic tool or in follow-up cases of VUR in children.
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Affiliation(s)
- Neda Enayati Zadeh
- Department of Radiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Simin Sadeghi-Bojd
- Children and Adolescents Health Research Center, Research Institute of Cellular and Molecular Science in Infectious Diseases, Zahedan University of Medical Science's, Zahedan, Iran
| | - Alireza Ansari-Moghaddam
- Health Promotion Research Center, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Amin Mashhadi
- Department of Radiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mohadeseh Zadehmir
- Department of Radiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
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17
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Abstract
Vesicoureteral reflux (VUR) is the commonest congenital anomaly of urinary tract in children. It is mostly diagnosed after a urinary tract infection or during evaluation for congenital anomalies of the kidney and urinary tract. High-grade VUR, recurrent pyelonephritis, and delayed initiation of antibiotic treatment are important risk factors for renal scarring. The management of VUR depends on multiple factors and may include surveillance only or antimicrobial prophylaxis; very few patients with VUR need surgical correction. Patients with renal scarring should be monitored for hypertension and those with significant scarring should also be monitored for proteinuria and chronic kidney disease.
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Affiliation(s)
- Tej K Mattoo
- Department of Pediatrics, Wayne State University School of Medicine, 400 Mack Avenue, Suite 1 East, Detroit, MI 48201, USA.
| | - Dunya Mohammad
- Pediatric Nephrology, University of South Alabama, 1601 Center Street, Suite 1271, Mobile, AL 36604, USA
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18
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Connaughton DM, Hildebrandt F. Disease mechanisms of monogenic congenital anomalies of the kidney and urinary tract American Journal of Medical Genetics Part C. AMERICAN JOURNAL OF MEDICAL GENETICS. PART C, SEMINARS IN MEDICAL GENETICS 2022; 190:325-343. [PMID: 36208064 PMCID: PMC9618346 DOI: 10.1002/ajmg.c.32006] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 07/14/2022] [Accepted: 09/16/2022] [Indexed: 11/05/2022]
Abstract
Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is a developmental disorder of the kidney and/or genito-urinary tract that results in end stage kidney disease (ESKD) in up to 50% of children. Despite the congenital nature of the disease, CAKUT accounts for almost 10% of adult onset ESKD. Multiple lines of evidence suggest that CAKUT is a Mendelian disorder, including the observation of familial clustering of CAKUT. Pathogenesis in CAKUT is embryonic in origin, with disturbances of kidney and urinary tract development resulting in a heterogeneous range of disease phenotypes. Despite polygenic and environmental factors being implicated, a significant proportion of CAKUT is monogenic in origin, with studies demonstrating single gene defects in 10%-20% of patients with CAKUT. Here, we review monogenic disease causation with emphasis on the etiological role of gene developmental pathways in CAKUT.
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Affiliation(s)
- Dervla M Connaughton
- Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada
- Department of Medicine, Division of Nephrology, London Health Sciences Centre, London, Ontario, Canada
| | - Friedhelm Hildebrandt
- Department of Pediatrics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
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19
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Gupta M, Phan TLT, Bunnell HT, Beheshti R. Obesity Prediction with EHR Data: A deep learning approach with interpretable elements. ACM TRANSACTIONS ON COMPUTING FOR HEALTHCARE 2022; 3:32. [PMID: 35756858 PMCID: PMC9221869 DOI: 10.1145/3506719] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Accepted: 12/01/2021] [Indexed: 06/07/2023]
Abstract
Childhood obesity is a major public health challenge. Early prediction and identification of the children at an elevated risk of developing childhood obesity may help in engaging earlier and more effective interventions to prevent and manage obesity. Most existing predictive tools for childhood obesity primarily rely on traditional regression-type methods using only a few hand-picked features and without exploiting longitudinal patterns of children's data. Deep learning methods allow the use of high-dimensional longitudinal datasets. In this paper, we present a deep learning model designed for predicting future obesity patterns from generally available items on children's medical history. To do this, we use a large unaugmented electronic health records dataset from a large pediatric health system in the US. We adopt a general LSTM network architecture and train our proposed model using both static and dynamic EHR data. To add interpretability, we have additionally included an attention layer to calculate the attention scores for the timestamps and rank features of each timestamp. Our model is used to predict obesity for ages between 3-20 years using the data from 1-3 years in advance. We compare the performance of our LSTM model with a series of existing studies in the literature and show it outperforms their performance in most age ranges.
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20
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Tang K, Liu M, Zhu Y, Zhang M, Niu C. The clinical application of ultrasonography with superb microvascular imaging-a review. JOURNAL OF CLINICAL ULTRASOUND : JCU 2022; 50:721-732. [PMID: 35358353 DOI: 10.1002/jcu.23210] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 03/19/2022] [Accepted: 03/22/2022] [Indexed: 06/14/2023]
Abstract
Superb microvascular imaging (SMI) is among the latest doppler ultrasound methods. It uses an advanced clutter filter to eliminate artifacts caused by breathing, movement and retains the low-speed blood signals in microvessels. The great advantage of SMI is that it can intuitively detect very slow blood signals in microvessels, providing clinicians with more significant information about flow distribution in the target area. Therefore, it is speculated that SMI has important application value. The purpose of this article is to outline the application of SMI in different parts of the body.
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Affiliation(s)
- Kui Tang
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Minghui Liu
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yun Zhu
- Department of Ultrasound Imaging, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Ming Zhang
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Chengcheng Niu
- Department of Ultrasound Diagnosis, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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The causes and consequences of paediatric kidney disease on adult nephrology care. Pediatr Nephrol 2022; 37:1245-1261. [PMID: 34389906 DOI: 10.1007/s00467-021-05182-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 05/29/2021] [Accepted: 06/01/2021] [Indexed: 10/20/2022]
Abstract
Adult nephrologists often look after patients who have been diagnosed with kidney disease in childhood. This does present unique challenges to the adult nephrologist, who may be unfamiliar with the underlying cause of kidney disease as well as the complications of chronic kidney disease (CKD) that may have accumulated during childhood. This review discusses common causes of childhood CKD, in particular congenital anomalies of the kidney and urinary tract (CAKUT), autosomal dominant tubulointerstitial kidney disease (ADTKD), polycystic kidney disease, hereditary stone disease, nephrotic syndrome and atypical haemolytic uraemic syndrome. The long-term consequences of childhood CKD, such as the cardiovascular consequences, cognition and education as well as bone health, nutrition and growth are also discussed.
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22
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Chang JW, Liu CS, Tsai HL. Vesicoureteral Reflux in Children with Urinary Tract Infections in the Inpatient Setting in Taiwan. Clin Epidemiol 2022; 14:299-307. [PMID: 35309102 PMCID: PMC8925909 DOI: 10.2147/clep.s346645] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 01/28/2022] [Indexed: 11/23/2022] Open
Abstract
Purpose Children with vesicoureteral reflux (VUR) are at an increased risk of recurrent urinary tract infections (UTIs). Early detection and treatment of VUR are important to prevent renal function impairment. Therefore, the aims of this study were to determine the epidemiology of VUR and to identify clinical factors associated with VUR in Taiwanese children with a first documented UTI. Patients and Methods We conducted this nationwide retrospective study using the Longitudinal Health Insurance Database 2010. Children ≤6 years of age who were admitted and received intravenous antibiotics for a newly diagnosed UTI were included. Multivariate logistic regression analysis was used to identify independent factors associated with VUR. Results Overall, 388 (10.2%) of the children had VUR. The median (interquartile range) age at diagnosis of VUR was 0.5 (0.3–1.3) years. Among the children with VUR, the age at first UTI and the age at diagnosis of VUR were significant lower in the males than in the females. Age ≤1 year at the first UTI (odds ratio (OR), 1.3; 95% confidence interval (CI): 1.0–1.7), renal agenesis and dysgenesis (OR, 4.1; 95% CI: 1.3–13.1), hydronephrosis (OR, 2.2; 95% CI: 1.7–2.9), duplex collecting system/ectopic kidney/ectopic ureter (OR, 13.0; 95% CI: 8.1–20.8), neuropathic bladder (OR, 4.7; 95% CI: 2.0–11.1) and spina bifida (OR, 5.9; 95% CI: 1.3–27.8) were independent factors for VUR. Conclusion The children with VUR were more likely to have small kidneys and progression to end-stage renal disease. VUR was common in the children with a UTI and who were ≤1 year of age. Clinicians should arrange ultrasound to diagnose urinary tract anomalies. Infants with urinary tract anomalies, neuropathic bladder and spina bifida should receive further voiding cystourethrography to diagnose VUR early, as this may help to prevent renal damage.
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Affiliation(s)
- Jei-Wen Chang
- Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chin-Su Liu
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Hsin-Lin Tsai
- Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
- Correspondence: Hsin-Lin Tsai, Division of Pediatric Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou District, Taipei City, Taiwan, Tel +886-2-2875-2101, Fax +886-2-2875-7105, Email
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Development and Validation of a Scoring System for Assessment of Clinical Failure after Pediatric Robot-Assisted Laparoscopic Extravesical Ureteral Reimplantation: A Multi-Center Study. J Clin Med 2022; 11:jcm11051327. [PMID: 35268417 PMCID: PMC8910908 DOI: 10.3390/jcm11051327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Revised: 02/17/2022] [Accepted: 02/25/2022] [Indexed: 02/04/2023] Open
Abstract
We aimed to develop and validate a scoring system as an objective assessment tool for predicting clinical failure after pediatric robotic extravesical ureteral reimplantation. Data for this multi-institutional retrospective cohort was obtained from two tertiary referral hospitals. We defined clinical failure as incomplete radiographic resolution or post-operative febrile UTI. Patients were stratified into low, intermediate, and high-risk groups according to the score. External validation was performed using the model projected to the external validation cohort. An amount of 115 renal units in the development cohort and 46 renal units in the validation cohort were analyzed. The prediction score was calculated with weighted points to each variable according to their regression coefficient as age (year) + BMI + BBD times 10 + VUR grade times 7 + console time (h) + hospital stay times 6. The C-index of our scoring system was 0.850 and 0.770 in the development and validation cohorts, respectively. Clinical failure was significantly different among risk groups: 0% (low-risk), 3.3% (intermediate-risk), and 22.2% (high-risk) (p = 0.004) in the development cohort. A novel scoring system using multiple pre- and intra-operative variables provides a prediction of children at risk of failure after robotic extravesical ureteral reimplantation.
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Brescacin A, Iesari S, Guzzo S, Alfieri CM, Darisi R, Perego M, Puliatti C, Ferraresso M, Favi E. Allograft Vesicoureteral Reflux after Kidney Transplantation. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:81. [PMID: 35056389 PMCID: PMC8780114 DOI: 10.3390/medicina58010081] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/31/2021] [Accepted: 01/04/2022] [Indexed: 01/06/2023]
Abstract
Allograft vesicoureteral reflux (VUR) is a leading urological complication of kidney transplantation. Despite the relatively high incidence, there is a lack of consensus regarding VUR risk factors, impact on renal function, and management. Dialysis vintage and atrophic bladder have been recognized as the most relevant recipient-related determinants of post-transplant VUR, whilst possible relationships with sex, age, and ureteral implantation technique remain debated. Clinical manifestations vary from an asymptomatic condition to persistent or recurrent urinary tract infections (UTIs). Voiding cystourethrography is widely accepted as the gold standard diagnostic modality, and the reflux is generally graded following the International Reflux Study Committee Scale. Long-term transplant outcomes of recipients with asymptomatic grade I-III VUR are yet to be clarified. On the contrary, available data suggest that symptomatic grade IV-V VUR may lead to progressive allograft dysfunction and premature transplant loss. Therapeutic options include watchful waiting, prolonged antibiotic suppression, sub-mucosal endoscopic injection of dextranomer/hyaluronic acid copolymer at the site of the ureteral anastomosis, and surgery. Indication for specific treatments depends on recipient's characteristics (age, frailty, compliance with antibiotics), renal function (serum creatinine concentration < 2.5 vs. ≥ 2.5 mg/dL), severity of UTIs, and VUR grading (grade I-III vs. IV-V). Current evidence supporting surgical referral over more conservative strategies is weak. Therefore, a tailored approach should be preferred. Properly designed studies, with adequate sample size and follow-up, are warranted to clarify those unresolved issues.
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Affiliation(s)
- Alessandra Brescacin
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (A.B.); (S.I.); (S.G.); (R.D.); (M.P.); (E.F.)
| | - Samuele Iesari
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (A.B.); (S.I.); (S.G.); (R.D.); (M.P.); (E.F.)
- Pôle de Chirurgie Expérimentale et Transplantation, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200 Brussels, Belgium
| | - Sonia Guzzo
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (A.B.); (S.I.); (S.G.); (R.D.); (M.P.); (E.F.)
| | - Carlo Maria Alfieri
- Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy
| | - Ruggero Darisi
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (A.B.); (S.I.); (S.G.); (R.D.); (M.P.); (E.F.)
| | - Marta Perego
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (A.B.); (S.I.); (S.G.); (R.D.); (M.P.); (E.F.)
| | - Carmelo Puliatti
- Division of General Surgery, Transplant Surgery Unit, Parma University Hospital, 43126 Parma, Italy;
| | - Mariano Ferraresso
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (A.B.); (S.I.); (S.G.); (R.D.); (M.P.); (E.F.)
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy
| | - Evaldo Favi
- General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; (A.B.); (S.I.); (S.G.); (R.D.); (M.P.); (E.F.)
- Department of Clinical Sciences and Community Health, Università degli Studi di Milano, 20122 Milan, Italy
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Majumdar S, Gupta S, Krishnamurthy S. Multifarious applications of bioactive glasses in soft tissue engineering. Biomater Sci 2021; 9:8111-8147. [PMID: 34766608 DOI: 10.1039/d1bm01104a] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Tissue engineering (TE), a new paradigm in regenerative medicine, repairs and restores the diseased or damaged tissues and eliminates drawbacks associated with autografts and allografts. In this context, many biomaterials have been developed for regenerating tissues and are considered revolutionary in TE due to their flexibility, biocompatibility, and biodegradability. One such well-documented biomaterial is bioactive glasses (BGs), known for their osteoconductive and osteogenic potential and their abundant orthopedic and dental clinical applications. However, in the last few decades, the soft tissue regenerative potential of BGs has demonstrated great promise. Therefore, this review comprehensively covers the biological application of BGs in the repair and regeneration of tissues outside the skeleton system. BGs promote neovascularization, which is crucial to encourage host tissue integration with the implanted construct, making them suitable biomaterial scaffolds for TE. Moreover, they heal acute and chronic wounds and also have been reported to restore the injured superficial intestinal mucosa, aiding in gastroduodenal regeneration. In addition, BGs promote regeneration of the tissues with minimal renewal capacity like the heart and lungs. Besides, the peripheral nerve and musculoskeletal reparative properties of BGs are also reported. These results show promising soft tissue regenerative potential of BGs under preclinical settings without posing significant adverse effects. Albeit, there is limited bench-to-bedside clinical translation of elucidative research on BGs as they require rigorous pharmacological evaluations using standardized animal models for assessing biomolecular downstream pathways.
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Affiliation(s)
- Shreyasi Majumdar
- Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, India.
| | - Smriti Gupta
- Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, India.
| | - Sairam Krishnamurthy
- Neurotherapeutics Laboratory, Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi-221005, India.
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Bartik Z, Sillén U, Östensson M, Fransson S, Djos A, Sjöberg R, Martinsson T. A genome‑wide scan to locate regions associated with familial vesicoureteral reflux. Exp Ther Med 2021; 23:92. [PMID: 34976134 PMCID: PMC8674978 DOI: 10.3892/etm.2021.11015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 07/06/2021] [Indexed: 11/05/2022] Open
Abstract
Vesicoureteral reflux (VUR) is a congenital malformation carrying a high risk of recurrent urinary tract infections (UTI) and, at worst, chronic renal failure. Familial clustering implies a genetic etiology, but studies during the past few decades have demonstrated a causal gene variant in <10% of patients with VUR. The aim of the present study was to search for fully or partially shared ancestral haplotypes in 14 families from south-western Sweden with at least three affected members. High-density single nucleotide polymorphism microarray was used for genotyping prior to analysis with a compatibility matching method developed in-house, and the analysis of copy number variations (CNV). No single unique haplotype was revealed to be shared by the families, thereby excluding a common ancestry and founder mutations as a probable cause of VUR. After evaluation of haplotypes shared by subsets of families, a haplotype shared by nine families was found to be of particular interest. This haplotype, located at chromosomal region 4q21.21, harbours two tentative candidate genes (bone morphogenetic protein 3 and fibroblast growth factor 5), both expressed in metanephros and with known functions during nephrogenesis. As to CNV, only one family had a specific CNV shared by all affected members. This was a focal deletion at 5q31.1 including follistatin-like 4, a gene without a previous known connection to VUR. These data demonstrated the genetic heterogeneity of VUR and indicated that an interaction of environmental and genetic factors, including non-coding and epigenetic regulators, all contribute to the complexity of VUR.
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Affiliation(s)
- Zsuzsa Bartik
- Department of Pediatric Surgery, Pediatric Uronephrology Center, The Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE‑41685 Gothenburg, Sweden
| | - Ulla Sillén
- Department of Pediatric Surgery, Pediatric Uronephrology Center, The Queen Silvia Children's Hospital, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE‑41685 Gothenburg, Sweden
| | - Malin Östensson
- Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, SE‑40530 Gothenburg, Sweden
| | - Susanne Fransson
- Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE‑40530 Gothenburg, Sweden
| | - Anna Djos
- Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE‑40530 Gothenburg, Sweden
| | - Rosmarie Sjöberg
- Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE‑40530 Gothenburg, Sweden
| | - Tommy Martinsson
- Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, SE‑40530 Gothenburg, Sweden
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Hsu CN, Tain YL. The First Thousand Days: Kidney Health and Beyond. Healthcare (Basel) 2021; 9:1332. [PMID: 34683012 PMCID: PMC8544398 DOI: 10.3390/healthcare9101332] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Revised: 09/25/2021] [Accepted: 10/03/2021] [Indexed: 12/12/2022] Open
Abstract
The global burden of chronic kidney disease (CKD) is rising. A superior strategy to advance global kidney health is required to prevent and treat CKD early. Kidney development can be impacted during the first 1000 days of life by numerous factors, including malnutrition, maternal illness, exposure to chemicals, substance abuse, medication use, infection, and exogenous stress. In the current review, we summarize environmental risk factors reported thus far in clinical and experimental studies relating to the programming of kidney disease, and systematize the knowledge on common mechanisms underlying renal programming. The aim of this review is to discuss the primary and secondary prevention actions for enhancing kidney health from pregnancy to age 2. The final task is to address the potential interventions to target renal programming through updating animal studies. Together, we can enhance the future of global kidney health in the first 1000 days of life.
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Affiliation(s)
- Chien-Ning Hsu
- Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan;
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - You-Lin Tain
- Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
- Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
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I El-Hallous E, Alharthi AA, Gaber A, M Hassan M. Molecular Screening of PAX2 Gene Polymorphism in Primary Vesicoureteral Reflux Patients in Taif Governorate, KSA. Pak J Biol Sci 2021; 24:492-499. [PMID: 34486308 DOI: 10.3923/pjbs.2021.492.499] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
<b>Background and Objective:</b> Primary Nonsyndromic Vesicoureteral Reflux (PVUR) is a widespread genetic malformation and considered a prevalent Congenital Abnormality of the Kidney and Urinary Tract (CAKUT). Mutations in the <i>PAX2 </i>gene have been associated with abnormalities in the kidney extending from CAKUT to oncogenic processes. The present study analyzes the <i>PAX2</i> polymorphisms and their association with primary VUR in Saudi children patients from the Taif governorate. <b>Materials and Methods:</b> Fifteen children with primary VUR were identified and screened for gene mutations in the <i>PAX2</i> gene by direct sequencing method of purified Polymerase Chain Reaction (PCR) products of all exons to elucidate the correlation between <i>PAX2</i> gene and VUR. <b>Results:</b> Seven new variants have been defined. Three polymorphic missense variants in homozygous genotype form were found in intron 8 and detected in eight patients, One missense mutation was found in exon 10 in the site of transactivation domain and detected in ten patients and <i>in-silico</i> analysis predicted it as a pathogenic one, Three mutations were found in exon 11 and detected in all patients as a compound homozygous. <b>Conclusion:</b> <i>PAX2</i>is important for normal kidney development and mutations in the gene possibly lead to disturbance in the protein structure and could be non-functional thus mutations in <i>PAX2</i> may be one of the causes of PVUR in Saudi Arabia. Further investigation is necessary to understand the aetiology of disease and maybe other genes implicated in VUR.
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Yang SS, Tsai JD, Kanematsu A, Han CH. Asian guidelines for urinary tract infection in children. J Infect Chemother 2021; 27:1543-1554. [PMID: 34391623 DOI: 10.1016/j.jiac.2021.07.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 06/08/2021] [Accepted: 07/11/2021] [Indexed: 11/25/2022]
Abstract
The followings are the level of evidence (LE) and grade of recommendation (GR) on pediatric UTI in Asia. Classification according to the sites of infection (lower versus upper tract), the number of episode (first versus recurrent), the severity (simple versus severe), or the existence of complicating factor (uncomplicated versus complicated) is useful to differentiate children with UTI whether they are at risk of renal damage or not (LE: 2, GR: B). Diagnosis of UTI requires both urinalysis that suggests infection and positive urine culture (LE:3, GR B). For pre-toilet trained children, urine specimen for culture should be collected by urethral catheterization or suprapubic aspiration. For toilet trained children, midstream clean catch urine is reliable (LE: 3, GR: A). Urine culture is considered positive if it demonstrates growth of a single bacterium with the following colony counts: (1) any growth by suprapubic aspiration, (2) >5 × 104 CFU/ml by urethral catheterization, or (3) >105 CFU/ml by midstream clean catch (LE:3, GR: B). For children with febrile UTI, renal and bladder ultrasonography (RBUS) should be routinely performed as soon as possible (LE: 3, GR: C). RBUS should be followed up 6 months later in children with acute pyelonephritis and/or VUR (LE: 3, GR: C). Acute DMSA scan can be performed when severe acute pyelonephritis or congenital hypodysplasia is noted on RBUS or when the diagnosis of UTI is in doubt by the clinical presentation (LE: 3, GR: C). Late DMSA scan (>6 months after the febrile UTI) can be performed in children with severe acute pyelonephritis, high-grade VUR, recurrent febrile UTIs, or abnormal renal parenchyma on the follow-up RBUS (LE: 3, GR: C). Top-down or bottom-up approach for febrile UTI is suggested for the diagnosis of VUR. For top-down approach, VCUG should not be performed routinely for children after the first febrile UTI. VCUG is indicated when abnormalities are apparent on either RBUS or DMSA scan or both (LE: 2, GR: B). VCUG is also suggested after a repeat febrile UTI (LE:2, GR: B). Appropriate antibiotic should be given immediately after urine specimen for culture has been obtained (LE:2, GR: A). Initiating therapy with oral or parenteral antibiotics is equally efficacious for children (>3 months) with uncomplicated UTI (LE: 2: GR: A). The choice of empirical antibiotic agents is guided by the expected pathogen and the local resistance patterns (LE: 2, GR: A). For children with febrile UTI, the total course of antibiotic therapy should be 7-14 days (LE: 2, GR: B). Circumcision may, but not definitively, reduce the risk of febrile UTI in males and breakthrough febrile UTI in males with VUR. Circumcision should be offered to uncircumcised boys with febrile UTI and VUR in countries where circumcision is accepted by the general population (LE: 3, GR: B), while in countries where childhood circumcision is rarely performed, other measures for febrile UTI/VUR should be the preferred choice (LE: 4, GR: C). Bladder bowel dysfunction (BBD) is one of the key factors of progression of renal scarring (LE: 2). Early recognition and management of BBD are important in prevention of UTI recurrence (LE:2, GR: A). Antibiotic prophylaxis to prevent recurrent febrile UTI is indicated in children with moderate to high grade (III-V) VUR (LE: 1b, GR: A). Surgical intervention may be used to treat VUR in the setting of recurrent febrile UTI because it has been shown to decrease the incidence of recurrent pyelonephritis (LE: 2, GR: B).
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Affiliation(s)
- Stephen S Yang
- Division of Urology, Taipei Tzu Chi Hospital, Medical Foundation, New Taipei, Taiwan; Buddhist Tzu Chi University, Hualien, Taiwan.
| | - Jeng-Daw Tsai
- Department of Medicine, Mackay Medical College, Taiwan; Department of Pediatric Nephrology, MacKay Children's Hospital, Taiwan; Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan; Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taiwan
| | | | - Chang-Hee Han
- Department of Urology, Uijeongbu ST. Mary's Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Republic of Korea
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Radiation exposure to infants undergoing voiding cystourethrography: The importance of the digital imaging technology. Phys Med 2021; 85:123-128. [PMID: 34000681 DOI: 10.1016/j.ejmp.2021.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2021] [Revised: 04/22/2021] [Accepted: 05/03/2021] [Indexed: 11/21/2022] Open
Abstract
PURPOSE To determine the radiation burden to infants undergoing voiding cystourethrography (VCUG) in a single institution and investigate the effect of shifting from analogue to digital imaging that allowed the use of a radiography-free examination protocol. METHODS Anthropometric and exposure data were prospectively collected for 35 consecutive infants undergoing VCUG on a digital system with a standardized examination protocol not including radiographs. Thermoluminescent dosimeters were used to determine entrance-skin dose. Monte Carlo simulations and patient-specific anthropomorphic phantoms were employed to determine organ/tissue doses and effective dose (ED). The associated theoretical risk of radiation-induced cancer was determined and compared to the nominal risk of cancer induction. The radiation burden from VCUG on a modern digital system with a contemporary examination protocol was compared to corresponding data reported previously for an analogue system in the same institution. RESULTS The median ED from VCUG was found 47 μSv. The associated total life attributable risk of radiation-induced cancer was found 10x10-6 and 13x10-6 for boys and girls, respectively. VCUG was found to increase the nominal risk of cancer by a factor of 1.000025 in boys and 1.000034 in girls. Shifting from analogue to digital imaging system resulted in 89% reduction of the radiation burden from VCUG. CONCLUSION The theoretical radiation risks for infants undergoing VCUG using a modern digital imaging system and a radiography-free protocol were found to be minor. The transition from analogue to digital equipment resulted in considerable reduction of the radiation burden from VCUG.
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Akarken I, Tarhan H, Arslan FD, Sarıtas S, Yavascan O, Sahin H, Tekgul S. Is endothelial glycocalyx damage a cause of renal scarring in vesicoureteral reflux with febrile urinary tract infection? Nephrol Ther 2021; 17:175-179. [PMID: 33941491 DOI: 10.1016/j.nephro.2021.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 01/01/2021] [Accepted: 01/05/2021] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Endothelial glycocalyx is a luminal layer which can be damaged by inflammatory agents or pathogens. The endothelial glycocalyx damage is thought to have a role in the formation of renal scars in children who have febrile urinary tract infection and vesicoureteral reflux. This study aimed to compare the blood levels of endothelial glycocalyx components heparan sulfate and Syndecan-1 in children with and without renal scarring due to vesicoureteral reflux-associated febrile urinary tract infection. MATERIALS AND METHODS Data of the patients diagnosed with vesicoureteral reflux without renal scarring (Group 1), patients with vesicoureteral reflux and renal scarring (Group 2), and completely healthy children (Group 3) were retrospectively reviewed. Blood levels of heparan sulfate and Syndecan-1 were measured and the results were compared. RESULTS The entire cohort consisted of 90 patients; there were 30 patients in each group. Mean patient age was 49.7±18.0 months. Mean serum heparan sulfate (42.90±18.90 ng/mL) and Syndecan-1 (37.59±13.77 ng/mL) levels of Group 2 were significantly higher than those of other groups. The cut-off value for heparan sulfate was 35.17 ng/mL, with a 63% sensitivity and 86% specificity. The cut-off value for Syndecan-1 was 29.99 ng/mL with a 70% sensitivity and 80% specificity. CONCLUSION Our findings indicate that blood levels of heparan sulfate and Syndecan-1 could be related with renal scarring in patients with vesicoureteral reflux, especially in the setting of febrile urinary tract infection. However, due to their low sensitivity, these biomarkers should be used along with clinical data.
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Affiliation(s)
- Ilker Akarken
- Mugla Sıtkı Kocman University, School of medicine, Department of urology, Turkey
| | - Huseyin Tarhan
- Mugla Sıtkı Kocman University, School of medicine, Department of urology, Turkey.
| | - Fatma Demet Arslan
- Izmir Tepecik Education and Research Hospital, Department of biochemistry, Turkey
| | - Serdar Sarıtas
- Izmir Tepecik Education and Research Hospital, Department of pediatric nephrology, Turkey
| | - Onder Yavascan
- Medipol University, School of medicine, Department of pediatric nephrology, Turkey
| | - Hayrettin Sahin
- Mugla Sıtkı Kocman University, School of medicine, Department of urology, Turkey
| | - Serdar Tekgul
- Hacettepe University, School of medicine, Department of urology, Turkey
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Verbitsky M, Krithivasan P, Batourina E, Khan A, Graham SE, Marasà M, Kim H, Lim TY, Weng PL, Sánchez-Rodríguez E, Mitrotti A, Ahram DF, Zanoni F, Fasel DA, Westland R, Sampson MG, Zhang JY, Bodria M, Kil BH, Shril S, Gesualdo L, Torri F, Scolari F, Izzi C, van Wijk JA, Saraga M, Santoro D, Conti G, Barton DE, Dobson MG, Puri P, Furth SL, Warady BA, Pisani I, Fiaccadori E, Allegri L, Degl'Innocenti ML, Piaggio G, Alam S, Gigante M, Zaza G, Esposito P, Lin F, Simões-e-Silva AC, Brodkiewicz A, Drozdz D, Zachwieja K, Miklaszewska M, Szczepanska M, Adamczyk P, Tkaczyk M, Tomczyk D, Sikora P, Mizerska-Wasiak M, Krzemien G, Szmigielska A, Zaniew M, Lozanovski VJ, Gucev Z, Ionita-Laza I, Stanaway IB, Crosslin DR, Wong CS, Hildebrandt F, Barasch J, Kenny EE, Loos RJ, Levy B, Ghiggeri GM, Hakonarson H, Latos-Bieleńska A, Materna-Kiryluk A, Darlow JM, Tasic V, Willer C, Kiryluk K, Sanna-Cherchi S, Mendelsohn CL, Gharavi AG. Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux. J Am Soc Nephrol 2021; 32:805-820. [PMID: 33597122 PMCID: PMC8017540 DOI: 10.1681/asn.2020050681] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 12/04/2020] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Vesicoureteral reflux (VUR) is a common, familial genitourinary disorder, and a major cause of pediatric urinary tract infection (UTI) and kidney failure. The genetic basis of VUR is not well understood. METHODS A diagnostic analysis sought rare, pathogenic copy number variant (CNV) disorders among 1737 patients with VUR. A GWAS was performed in 1395 patients and 5366 controls, of European ancestry. RESULTS Altogether, 3% of VUR patients harbored an undiagnosed rare CNV disorder, such as the 1q21.1, 16p11.2, 22q11.21, and triple X syndromes ((OR, 3.12; 95% CI, 2.10 to 4.54; P=6.35×10-8) The GWAS identified three study-wide significant and five suggestive loci with large effects (ORs, 1.41-6.9), containing canonical developmental genes expressed in the developing urinary tract (WDPCP, OTX1, BMP5, VANGL1, and WNT5A). In particular, 3.3% of VUR patients were homozygous for an intronic variant in WDPCP (rs13013890; OR, 3.65; 95% CI, 2.39 to 5.56; P=1.86×10-9). This locus was associated with multiple genitourinary phenotypes in the UK Biobank and eMERGE studies. Analysis of Wnt5a mutant mice confirmed the role of Wnt5a signaling in bladder and ureteric morphogenesis. CONCLUSIONS These data demonstrate the genetic heterogeneity of VUR. Altogether, 6% of patients with VUR harbored a rare CNV or a common variant genotype conferring an OR >3. Identification of these genetic risk factors has multiple implications for clinical care and for analysis of outcomes in VUR.
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Affiliation(s)
- Miguel Verbitsky
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - Priya Krithivasan
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | | | - Atlas Khan
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - Sarah E. Graham
- Department of Internal Medicine, Cardiology, University of Michigan, Ann Arbor, Michigan
| | - Maddalena Marasà
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - Hyunwoo Kim
- Department of Urology, Columbia University, New York, New York
| | - Tze Y. Lim
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - Patricia L. Weng
- Department of Pediatric Nephrology, University of California, Los Angeles Medical Center and University of California, Los Angeles Medical Center-Santa Monica, Los Angeles, California
| | | | - Adele Mitrotti
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
- Section of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Dina F. Ahram
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - Francesca Zanoni
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - David A. Fasel
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - Rik Westland
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
- Department of Pediatric Nephrology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands
| | - Matthew G. Sampson
- Division of Nephrology, Boston Children’s Hospital, Boston, Massachusetts
| | - Jun Y. Zhang
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - Monica Bodria
- Division of Nephrology, Dialysis, Transplantation, and Laboratory on Pathophysiology of Uremia, Istituto G. Gaslini, Genoa, Italy
| | - Byum Hee Kil
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - Shirlee Shril
- Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
| | - Loreto Gesualdo
- Section of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Fabio Torri
- Department of Pediatric Surgery, Spedali Civili Children’s Hospital of Brescia, Brescia, Italy
| | - Francesco Scolari
- Chair and Division of Nephrology, University and Spedali Civili Hospital, Brescia, Italy
| | - Claudia Izzi
- Division of Nephrology and Department of Obstetrics and Gynecology, ASST Spedali Civili of Brescia, Brescia, Italy
| | - Joanna A.E. van Wijk
- Department of Pediatric Nephrology, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands
| | - Marijan Saraga
- Department of Pediatrics, University Hospital of Split, Split, Croatia
- School of Medicine, University of Split, Split, Croatia
| | - Domenico Santoro
- Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Giovanni Conti
- Department of Pediatric Nephrology, Azienda Ospedaliera Universitaria “G. Martino,” Messina, Italy
| | - David E. Barton
- University College Dublin School of Medicine, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland
- Department of Clinical Genetics, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland
| | - Mark G. Dobson
- Department of Clinical Genetics, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland
- National Children’s Research Centre, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland
| | - Prem Puri
- National Children’s Research Centre, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland
- Department of Pediatric Surgery, Beacon Hospital, University College Dublin, Dublin, Ireland
| | - Susan L. Furth
- Division of Nephrology, Departments of Pediatrics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Bradley A. Warady
- Division of Nephrology, Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Children’s Mercy Kansas City, Kansas City, Missouri
| | - Isabella Pisani
- Nephrology Unit, Parma University Hospital and Department of Medicine and Surgery, Parma University Medical School, Parma, Italy
| | - Enrico Fiaccadori
- Nephrology Unit, Parma University Hospital and Department of Medicine and Surgery, Parma University Medical School, Parma, Italy
| | - Landino Allegri
- Nephrology Unit, Parma University Hospital and Department of Medicine and Surgery, Parma University Medical School, Parma, Italy
| | - Maria Ludovica Degl'Innocenti
- Division of Nephrology, Dialysis, Transplantation, and Laboratory on Pathophysiology of Uremia, Istituto G. Gaslini, Genoa, Italy
| | - Giorgio Piaggio
- Division of Nephrology, Dialysis, Transplantation, and Laboratory on Pathophysiology of Uremia, Istituto G. Gaslini, Genoa, Italy
| | - Shumyle Alam
- Department of Pediatric Urology, Columbia University College of Physicians and Surgeons, New York, New York
| | - Maddalena Gigante
- Section of Nephrology, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Gianluigi Zaza
- Renal and Dialysis Unit, Department of Medicine, School of Medicine, University of Verona, Verona, Italy
| | - Pasquale Esposito
- Department of Internal Medicine, Nephrology, Dialysis and Transplantation Clinics, Genoa University and IRCCS Policlinico San Martino, Genova, Italy
| | - Fangming Lin
- Division of Pediatric Nephrology, Department of Pediatrics, Columbia University, New York, New York
| | - Ana Cristina Simões-e-Silva
- Department of Pediatrics, Unit of Pediatric Nephrology, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Andrzej Brodkiewicz
- Department of Pediatrics, Child Nephrology, Dialysotheraphy and Management of Acute Poisoning, Pomeranian Medical University, Szczecin, Poland
| | - Dorota Drozdz
- Department of Pediatric Nephrology and Hypertension, Jagiellonian University Medical College, Krakow, Poland
| | - Katarzyna Zachwieja
- Department of Pediatric Nephrology and Hypertension, Jagiellonian University Medical College, Krakow, Poland
| | - Monika Miklaszewska
- Department of Pediatric Nephrology and Hypertension, Jagiellonian University Medical College, Krakow, Poland
| | - Maria Szczepanska
- Department of Pediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Katowice, Poland
| | - Piotr Adamczyk
- Department of Pediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, Katowice, Poland
| | - Marcin Tkaczyk
- Department of Pediatrics, Immunology and Nephrology, Polish Mother’s Memorial Hospital Research Institute, Lodz, Poland
| | - Daria Tomczyk
- Department of Pediatrics, Immunology and Nephrology, Polish Mother’s Memorial Hospital Research Institute, Lodz, Poland
| | - Przemyslaw Sikora
- Department of Pediatric Nephrology, Medical University of Lublin, Lublin, Poland
| | | | - Grazyna Krzemien
- Department of Pediatrics and Nephrology, Medical University of Warsaw, Poland
| | | | - Marcin Zaniew
- Department of Pediatrics, University of Zielona Góra, Zielona Góra, Poland
| | - Vladimir J. Lozanovski
- University Clinic for General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- University Children’s Hospital, Medical Faculty of Skopje, Skopje, Macedonia
| | - Zoran Gucev
- University Children’s Hospital, Medical Faculty of Skopje, Skopje, Macedonia
| | | | - Ian B. Stanaway
- Department of Biomedical Informatics and Medical Education, University of Washington School of Medicine, Seattle, Washington
| | - David R. Crosslin
- Department of Biomedical Informatics and Medical Education, University of Washington School of Medicine, Seattle, Washington
| | - Craig S. Wong
- Division of Pediatric Nephrology, University of New Mexico Children’s Hospital, Albuquerque, New Mexico
| | - Friedhelm Hildebrandt
- Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts
| | - Jonathan Barasch
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
- Department of Urology, Columbia University, New York, New York
| | - Eimear E. Kenny
- Institute for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York
- Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
- Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Ruth J.F. Loos
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York
| | - Brynn Levy
- Department of Pathology and Cell Biology, Columbia University, New York, New York
| | - Gian Marco Ghiggeri
- Division of Nephrology, Dialysis, Transplantation, and Laboratory on Pathophysiology of Uremia, Istituto G. Gaslini, Genoa, Italy
| | - Hakon Hakonarson
- Center for Applied Genomics, The Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Anna Latos-Bieleńska
- Department of Medical Genetics, Poznan University of Medical Sciences, and NZOZ Center for Medical Genetics GENESIS, Poznan, Poland
| | - Anna Materna-Kiryluk
- Department of Medical Genetics, Poznan University of Medical Sciences, and NZOZ Center for Medical Genetics GENESIS, Poznan, Poland
| | - John M. Darlow
- Department of Clinical Genetics, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland
- National Children’s Research Centre, Our Lady’s Children’s Hospital Crumlin, Dublin, Ireland
| | - Velibor Tasic
- University Children’s Hospital, Medical Faculty of Skopje, Skopje, Macedonia
| | - Cristen Willer
- Department of Internal Medicine, Cardiology, University of Michigan, Ann Arbor, Michigan
- Department of Human Genetics, University of Michigan, Ann Arbor, Michigan
- Department of Computational Medicine and Bioinformatics, Ann Arbor, Michigan
| | - Krzysztof Kiryluk
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | - Simone Sanna-Cherchi
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
| | | | - Ali G. Gharavi
- Division of Nephrology, Department of Medicine, Columbia University, New York, New York
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Evaluation of the Diagnostic Value of Contrast-Enhanced Voiding Urosonography with Regard to the Further Therapy Regime and Patient Outcome-A Single-Center Experience in an Interdisciplinary Uroradiological Setting. ACTA ACUST UNITED AC 2021; 57:medicina57010056. [PMID: 33435420 PMCID: PMC7826578 DOI: 10.3390/medicina57010056] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2020] [Revised: 01/03/2021] [Accepted: 01/06/2021] [Indexed: 01/11/2023]
Abstract
Background and Objectives: Vesicoureteral reflux (VUR) describes a common pediatric anomaly in pediatric urology with a prevalence of 1-2%. In diagnostics, in addition to the gold standard of voiding cystourethrography (VCUG), contrast-enhanced urosonography (ceVUS) offers a radiation-free procedure, which, despite its advantages, is not yet widely used. In the present single-center study, subsequent therapeutic procedures and outcomes after ceVUS of 49 patients were investigated. The aim of the study is to investigate the efficacy of ceVUS with the intention of broader clinical implementation. Materials and Methods: Between 2016 and 2020, 49 patients were retrospectively included and received a ceVUS to evaluate VUR. With a distribution of 47:2 (95.9%), a clear female predominance was present. The age of the patients varied between 5 months and 60 years at the time of ceVUS. All examinations were all performed and subsequently interpreted by a single experienced radiologist (EFSUMB level 3). Results: Compared to intraoperative findings, ceVUS shows a sensitivity of 95.7% with a specificity of 100%. Allergic reactions to the contrast medium could not be observed. Conclusion: With its high sensitivity and intraoperative validation, ceVUS offers an excellent alternative to VCUG, the gold standard in the diagnosis of VUR. In addition, ceVUS is a radiation-free examination method with a low risk profile that offers an exceptional diagnostic tool in the diagnostic clarification of recurrent urinary tract infections with the suspected diagnosis of VUR and should also be included in the consideration of a diagnosis next to the established VCUG, especially in younger children.
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Siregar S, Kurniawan A, Mustafa A. Conservative management of vesicoureteral reflux: A literature review. UROLOGICAL SCIENCE 2021. [DOI: 10.4103/uros.uros_132_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Ureterovesical junction deformation during urine storage in the bladder and the effect on vesicoureteral reflux. J Biomech 2020; 113:110123. [DOI: 10.1016/j.jbiomech.2020.110123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Revised: 10/20/2020] [Accepted: 11/03/2020] [Indexed: 11/19/2022]
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36
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Kim YJ, Cho BS, Lee J, Ryu H, Byun H, Yeon M, Park Y, Oh C, Jeon Y. The ABCs of Voiding Cystourethrography. JOURNAL OF THE KOREAN SOCIETY OF RADIOLOGY 2020; 81:101-118. [PMID: 36238127 PMCID: PMC9432100 DOI: 10.3348/jksr.2020.81.1.101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 06/13/2019] [Accepted: 07/31/2019] [Indexed: 11/30/2022]
Abstract
Voiding cystourethrography (VCUG) demonstrates the anatomy of the urinary system and is used to detect the presence/absence of vesicoureteral reflux. It is the most important modality for urological fluoroscopic examination in children. For improved patient care, it is important to understand and perform VCUG appropriately. Therefore, an in-depth review of VCUG protocols and techniques has been presented herein. In addition, tips, tricks, and pitfalls associated with the technique have also been addressed.
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Affiliation(s)
- Yu Jin Kim
- Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea
| | - Bum Sang Cho
- Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea
- Department of Radiology, College of Medicine, Chungbuk National University, Cheongju, Korea
| | - Junghwan Lee
- Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea
| | - Hyeonmi Ryu
- Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea
| | - Honggwon Byun
- Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea
| | - Miran Yeon
- Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea
| | - Yeongtae Park
- Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea
| | - Changhoon Oh
- Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea
| | - Younghun Jeon
- Department of Radiology, Chungbuk National University Hospital, Cheongju, Korea
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Bilge I. Symptomatology and Clinic of Hydronephrosis Associated With Uretero Pelvic Junction Anomalies. Front Pediatr 2020; 8:520. [PMID: 33102401 PMCID: PMC7554633 DOI: 10.3389/fped.2020.00520] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Accepted: 07/22/2020] [Indexed: 12/25/2022] Open
Abstract
The most common cause of hydronephrosis in the pediatric age group is ureteropelvic junction-type hydronephrosis (UPJHN). Since the advent of widespread maternal ultrasound screening, clinical presentation of hydronephrosis associated with UPJ anomalies has changed dramatically. Today most cases are diagnosed in the prenatal period, and neonates present without signs or symptoms. For those who are not detected at birth, UPJHN eventually presents throughout childhood and even adulthood with various symptoms. Clinical picture of UPJHN highly depends on the presence and severity of obstruction, and whether it affects single or both kidneys. Abdominal or flank pain, abdominal mass, hematuria, kidney stones, urinary tract infections (UTI), and gastrointestinal discomfort are the main symptoms of UPJHN in childhood. Other less common findings in such patients are growth retardation, anemia, and hypertension. UTI is a relatively rare condition in UPJHN cases, but it may occur as pyelonephritis. Vesicoureteric reflux should be kept in mind as a concomitant pathology in pediatric UPJHN that develop febrile UTI. Although many UPJHN cases are known to improve over time, close clinical observation is critical in order to avoid irreversible kidney damage. The most appropriate approach is to follow-up the patients considering the presence of symptoms, the severity of hydronephrosis and the decrease in kidney function and, if necessary, to decide on early surgical intervention.
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Affiliation(s)
- Ilmay Bilge
- Division of Pediatric Nephrology, Department of Pediatrics, School of Medicine, Koc University, Istanbul, Turkey
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Voiding cystourethrography and 99MTC-MAG3 renal scintigraphy in pediatric vesicoureteral reflux: what is the role of indirect cystography? J Pediatr Urol 2019; 15:514.e1-514.e6. [PMID: 31285138 DOI: 10.1016/j.jpurol.2019.06.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2019] [Accepted: 06/06/2019] [Indexed: 11/21/2022]
Abstract
BACKGROUND Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children. Voiding cystourethrography (VCUG) is considered the reference standard for the diagnosis of VUR. Even if it is a secure and standardized technique, it is still an invasive method, hence, the effort to find an alternative method to diagnose VUR. The aim of the study is to evaluate the diagnostic accuracy of 99mTC-MAG3 scintigraphy with indirect cystography in detecting VUR and to estimate any interobserver variability in 99mTC-MAG3 scintigraphy interpretation. METHODS The authors retrospectively reviewed all the pediatric patients who underwent both a VCUG and a 99mTC-MAG3 renal scintigraphy at the study institution between 2012 and 2016. RESULTS A total of 86 children (and 168 renal units) were included. MAG3 scan revealed a sensitivity of 54% and a specificity of 90% with positive predictive value of 79% and negative predictive value of 73%. Each MAG3 scintigraphy was then independently and blindly evaluated by a pediatric urologist and two nuclear physicians. After revision, the concordance between VCUG and MAG3 in reflux cases dropped from 54% to 27% (on average), and the reviewers reclassified most examinations as non-conclusive. CONCLUSIONS 99mTC-MAG3 renal scintigraphy with indirect cystography showed low sensitivity in detecting VUR of any grade and cannot, therefore, be proposed as completely alternative to VCUG in the diagnosis of VUR. Moreover, MAG3 scintigraphy interpretation for the diagnosis of VUR has a very high interobserver variability, mostly because of the lack of a correct and complete voiding phase.
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Liang D, McHugh KM, Brophy PD, Shaikh N, Manak JR, Andrews P, Hakker I, Wang Z, Schwaderer AL, Hains DS. DNA copy number variations in children with vesicoureteral reflux and urinary tract infections. PLoS One 2019; 14:e0220617. [PMID: 31404082 PMCID: PMC6690579 DOI: 10.1371/journal.pone.0220617] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 07/19/2019] [Indexed: 11/18/2022] Open
Abstract
Vesicoureteral reflux (VUR) is a complex, heritable disorder. Genome-wide linkage analyses of families affected by VUR have revealed multiple genomic loci linked to VUR. These loci normally harbor a number of genes whose biologically functional variant is yet to be identified. DNA copy number variations (CNVs) have not been extensively studied at high resolution in VUR patients. In this study, we performed array comparative genomic hybridization (aCGH) on a cohort of patients with a history of both VUR and urinary tract infection (UTI) with the objective of identifying genetic variations responsible for VUR and/or UTI susceptibility. UTI/VUR-associated CNVs were identified by aCGH results from the 192 Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) patients compared to 683 controls. Rare, large CNVs that are likely pathogenic and lead to VUR development were identified using stringent analysis criteria. Because UTI is a common affliction with multiple risk factors, we utilized standard analysis to identify potential disease-modifying CNVs that can contribute to UTI risk. Gene ontology analysis identified that CNVs in innate immunity and development genes were enriched in RIVUR patients. CNVs affecting innate immune genes may contribute to UTI susceptibility in VUR patients and may provide the first step in assisting clinical medicine in determining adverse outcome risk in children with VUR.
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Affiliation(s)
- Dong Liang
- Department of Pediatrics, Indiana University, Indianapolis, IN, United States of America
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States of America
| | - Kirk M. McHugh
- Division of Anatomy, The Ohio State University, Columbus, OH, United States of America
| | - Pat D. Brophy
- Department of Pediatrics, University of Rochester Medical Center, Rochester, NY, United States of America
| | - Nader Shaikh
- Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, United States of America
| | - J. Robert Manak
- Departments of Biology and Pediatrics, University of Iowa, Iowa City, IA, United States of America
| | - Peter Andrews
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States of America
| | - Inessa Hakker
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States of America
| | - Zihua Wang
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States of America
| | - Andrew L. Schwaderer
- Department of Pediatrics, Indiana University, Indianapolis, IN, United States of America
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States of America
- Riley Hospital for Children at Indiana University Health, Indianapolis, IN, United States of America
| | - David S. Hains
- Department of Pediatrics, Indiana University, Indianapolis, IN, United States of America
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States of America
- Riley Hospital for Children at Indiana University Health, Indianapolis, IN, United States of America
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Friedmacher F, Puri P. Ureteral Obstruction After Endoscopic Treatment of Vesicoureteral Reflux: Does the Type of Injected Bulking Agent Matter? Curr Urol Rep 2019; 20:49. [DOI: 10.1007/s11934-019-0913-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Becerir T, Yüksel S, Evrengül H, Ergin A, Enli Y. Urinary excretion of pentraxin-3 correlates with the presence of renal scar following acute pyelonephritis in children. Int Urol Nephrol 2019; 51:571-577. [PMID: 30796728 DOI: 10.1007/s11255-019-02102-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 02/08/2019] [Indexed: 12/21/2022]
Abstract
PURPOSE Acute pyelonephritis is associated with considerable morbidity and potential for renal scarring. Pentraxin3 (PTX3) is a recently discovered mediator of inflammation. The objective of this study was to investigate the changes in serum and urine PTX3 levels in children who had a history of pyelonephritis and were diagnosed with renal parenchymal scar (RPS) and/or vesicoureteral reflux (VUR). METHODS The study included 88 children (31 males, 57 females) aged between 3 months and 18 years. The children included in the study were divided into four groups: VUR with RPS (Group 1), RPS without VUR (Group 2), VUR without RPS (Group 3), and healthy children without a history of hydronephrosis or UTI history (Group 4). After the initial evaluation, the participants were further divided into two more groups and re-evaluated: Children with RPS (Group 1 + 2), children without RPS (Group 3 + 4), children with VUR (Group 1 + 3), and children without VUR (Group 2 + 4). RESULTS We found that urine pentraxin 3 (uPTX3) and uPTX3/Creatinine levels were significantly higher in the groups with renal scar with or without VUR than the ones without RPS [mean uPTX3, 3.5 pg/ml (min-max 0.0022-12.3668) vs. 2.2 pg/ml (min-max 0.0022-18.5868) and uPTX3/creatinine, 10.5 pg/mg (min-max 0.0035-51.1) vs. 5.8 pg/mg (min-max 0.0004-78.7), p < 0.01]. uPTX3 levels were not different among the groups with and without VUR. In addition, serum PTX3 levels were not different among the groups. CONCLUSIONS We showed that urinary PTX3 increased only in patients with scarred kidneys. These results might be helpful to predict RPS due to past pyelonephritis.
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Affiliation(s)
- Tülay Becerir
- Department of Pediatric Nephrology, Namık Kemal University School of Medicine, 59030, Tekirdağ, Turkey
| | - Selcuk Yüksel
- Department of Pediatric Rheumatology and Nephrology, Pamukkale University School of Medicine, 20070, Kınıklı Yerleşkesi/Denizli, Turkey.
| | - Havva Evrengül
- Department of Pediatric Nephrology, Pamukkale University School of Medicine, 20070, Kınıklı Yerleşkesi/Denizli, Turkey
| | - Ahmet Ergin
- Department of Social Pediatrics, Pamukkale University School of Medicine, 20070, Kınıklı Yerleşkesi/Denizli, Turkey
| | - Yaşar Enli
- Department of Biochemistry, Pamukkale University School of Medicine, 20070, Kınıklı Yerleşkesi/Denizli, Turkey
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Widening the lens to childhood: relevance and lifetime risk of kidney failure. Curr Opin Nephrol Hypertens 2019; 28:233-237. [PMID: 30844883 DOI: 10.1097/mnh.0000000000000494] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Lifetime risk of outcomes is emerging as a highly relevant health indicator, even in the context of low absolute risk of disease progression in short time frames. Evidence to support this concept for kidney failure is increasing, with growing emphasis on the long-term impact of risk factors occurring early in life. RECENT FINDINGS Proteinuria and stage of chronic kidney disease (CKD) are now established predictors of CKD progression in children, and youth with type 2 diabetes are emerging as a group at significant risk. Recent population-based studies have also examined the lifetime risk of end-stage renal disease in individuals with any childhood CKD. A recent study found that even in the absence of biomarkers of renal injury, childhood CKD can increase the lifetime risk of end-stage renal disease four-fold, and up to 10-fold in adults less than 40 years of age. SUMMARY Children with CKD are at high lifetime risk of kidney failure and require follow-up. Identifying children at highest lifetime risk through the use of biomarkers and risk equations, and determining the optimal duration and intensity of follow-up requires further research.
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Woolf AS, Lopes FM, Ranjzad P, Roberts NA. Congenital Disorders of the Human Urinary Tract: Recent Insights From Genetic and Molecular Studies. Front Pediatr 2019; 7:136. [PMID: 31032239 PMCID: PMC6470263 DOI: 10.3389/fped.2019.00136] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2018] [Accepted: 03/22/2019] [Indexed: 12/13/2022] Open
Abstract
The urinary tract comprises the renal pelvis, the ureter, the urinary bladder, and the urethra. The tract acts as a functional unit, first propelling urine from the kidney to the bladder, then storing it at low pressure inside the bladder which intermittently and completely voids urine through the urethra. Congenital diseases of these structures can lead to a range of diseases sometimes associated with fetal losses or kidney failure in childhood and later in life. In some of these disorders, parts of the urinary tract are severely malformed. In other cases, the organs appear grossly intact yet they have functional deficits that compromise health. Human studies are beginning to indicate monogenic causes for some of these diseases. Here, the implicated genes can encode smooth muscle, neural or urothelial molecules, or transcription factors that regulate their expression. Furthermore, certain animal models are informative about how such molecules control the development and functional differentiation of the urinary tract. In future, novel therapies, including those based on gene transfer and stem cell technologies, may be used to treat these diseases to complement conventional pharmacological and surgical clinical therapies.
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Affiliation(s)
- Adrian S Woolf
- Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom.,Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom
| | - Filipa M Lopes
- Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom
| | - Parisa Ranjzad
- Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom
| | - Neil A Roberts
- Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology Medicine and Health, School of Biological Sciences, University of Manchester, Manchester, United Kingdom
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Jain S, Chen F. Developmental pathology of congenital kidney and urinary tract anomalies. Clin Kidney J 2018; 12:382-399. [PMID: 31198539 PMCID: PMC6543978 DOI: 10.1093/ckj/sfy112] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Indexed: 12/18/2022] Open
Abstract
Congenital anomalies of the kidneys or lower urinary tract (CAKUT) are the most common causes of renal failure in children and account for 25% of end-stage renal disease in adults. The spectrum of anomalies includes renal agenesis; hypoplasia; dysplasia; supernumerary, ectopic or fused kidneys; duplication; ureteropelvic junction obstruction; primary megaureter or ureterovesical junction obstruction; vesicoureteral reflux; ureterocele; and posterior urethral valves. CAKUT originates from developmental defects and can occur in isolation or as part of other syndromes. In recent decades, along with better understanding of the pathological features of the human congenital urinary tract defects, researchers using animal models have provided valuable insights into the pathogenesis of these diseases. However, the genetic causes and etiology of many CAKUT cases remain unknown, presenting challenges in finding effective treatment. Here we provide an overview of the critical steps of normal development of the urinary system, followed by a description of the pathological features of major types of CAKUT with respect to developmental mechanisms of their etiology.
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Affiliation(s)
- Sanjay Jain
- Division of Nephrology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
| | - Feng Chen
- Division of Nephrology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA
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Sivasubramanian K, Periyasamy V, Dienzo RA, Pramanik M. Hand-held, clinical dual mode ultrasound - photoacoustic imaging of rat urinary bladder and its applications. JOURNAL OF BIOPHOTONICS 2018; 11:e201700317. [PMID: 29341418 DOI: 10.1002/jbio.201700317] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Revised: 12/11/2017] [Accepted: 01/12/2018] [Indexed: 05/07/2023]
Abstract
Urinary bladder imaging is critical to diagnose urinary tract disorders, and bladder cancer. There is a great need for safe, non-invasive, and sensitive imaging technique which enables bladder imaging. Photoacoustic imaging is a rapidly growing imaging technique for various biological applications. It can be combined with clinical ultrasound imaging system for hand-held, dual modal ultrasound-photoacoustic real-time imaging. Structural (bladder wall) and functional (accretion of nanoparticles) bladder imaging is shown here with combined ultrasound and photoacoustic imaging in rats. Photoacoustic images of bladder wall is shown using black ink as the contrast agent. Chicken tissues were stacked on the abdomen of the animal to demonstrate the feasibility of photoacoustic imaging till a depth of 2 cm. Also, the feasibility of photoacoustic imaging for a common bladder disorder, vesicoureteral reflux is studied using urinary tract mimicking phantom. It is also shown that a clinical ultrasound system can be used for photoacoustic imaging of non-invasive clearance study of gold nanorods from circulation by monitoring the gradual accumulation of the gold nanorods in the bladder. The time taken for accumulation of nanorods in the bladder can be used as an indicator of the clearance rate of the nanoparticle circulation from the body.
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Affiliation(s)
| | - Vijitha Periyasamy
- School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore
| | - Rhonnie Austria Dienzo
- School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore
| | - Manojit Pramanik
- School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore
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Friedmacher F, Colhoun E, Puri P. Endoscopic Injection of Dextranomer/Hyaluronic Acid as First Line Treatment in 851 Consecutive Children with High Grade Vesicoureteral Reflux: Efficacy and Long-Term Results. J Urol 2018; 200:650-655. [PMID: 29551405 DOI: 10.1016/j.juro.2018.03.074] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2018] [Indexed: 10/17/2022]
Abstract
PURPOSE Endoscopic injection of dextranomer/hyaluronic acid is widely acknowledged as first line treatment of lower grade vesicoureteral reflux. We demonstrate its long-term efficacy and safety in eradicating high grade reflux. MATERIALS AND METHODS A total of 518 girls and 333 boys with a median age of 2.3 years (range 2 months to 13.7 years) underwent endoscopic correction of high grade vesicoureteral reflux using dextranomer/hyaluronic acid. Reflux was unilateral in 415 cases and bilateral in 436, comprising 1,287 refluxing units. Reflux was grade IV in 1,153 ureters (89.6%) and grade V in 134 (10.4%). 99mTechnetium-dimercaptosuccinic acid scintigraphy identified renal scarring in 317 patients (37.3%). Followup ultrasound and voiding cystourethrogram were performed 3 months after intervention and renal ultrasound yearly thereafter. Median followup was 8.5 years (range 6 months to 16 years). RESULTS Overall resolution rate after the first endoscopic injection was 69.5% (895 of 1,287 cases), with resolution in 70.4% of grade IV and 61.9% of grade V cases. Reflux resolved after a second injection in 259 cases (20.1%) and after a third injection in 133 (10.4%). Persistent reflux after initial treatment was significantly more common in patients younger than age 1 year and in individuals with renal scarring. No significant postoperative complications were observed and no patient required ureteral reimplantation. Following reflux resolution febrile urinary tract infection developed in 43 children (5.1%), including 24 (55.8%) during the first year, 15 (34.9%) during the second year and 4 (9.3%) during year 3 or later. Of these patients 6 had reflux recurrence and 8 had neocontralateral grade III reflux, which was successfully treated with a single endoscopic injection of dextranomer/hyaluronic acid. CONCLUSIONS Endoscopic injection of dextranomer/hyaluronic acid is an efficient and safe long-term treatment for grade IV and V vesicoureteral reflux, and can easily be repeated in patients with treatment failure with a high subsequent resolution rate.
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Affiliation(s)
- Florian Friedmacher
- National Children's Hospital, Tallaght, Ireland; National Children's Research Center, Our Lady's Children's Hospital, Crumlin, Ireland.
| | | | - Prem Puri
- National Children's Hospital, Tallaght, Ireland; National Children's Research Center, Our Lady's Children's Hospital, Crumlin, Ireland; Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland
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47
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Kaplan YC, Keskin-Arslan E, Küçüksolak G, Akyol F, Karadas B, Görgel SN, Kaya-Temiz T. Pregnancy outcomes after maternal use of thiocolchicoside: A case series. Reprod Toxicol 2018; 76:103-108. [PMID: 29378258 DOI: 10.1016/j.reprotox.2018.01.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2017] [Revised: 12/26/2017] [Accepted: 01/23/2018] [Indexed: 11/29/2022]
Abstract
OBJECTIVE The 2014 report by European Medicines Agency (EMA) restricted the use of thiocolchicoside for all reproductive-age women. In this study, we aim to expand the systematically-collected human data and discuss it within the frame provided by this report. METHODS We identified and evaluated the outcomes of 48 prospectively recorded pregnancies referred to Terafar (Teratology Information Service, Izmir, Turkey). RESULTS Of 42 pregnancies with first-trimester exposure and known outcomes, 31 resulted in live births, four in miscarriage and seven ended with elective terminations. There were 26 normal outcomes, two major and three minor congenital malformations among the live births. CONCLUSIONS Despite a number of limitations, our results and previous case series collectively strengthen the view that thiocolchicoside is unlikely to be a major teratogen. EMA's 2014 report should be revised to reflect this finding, while current restrictions on use should continue until more detailed safety information is available.
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Affiliation(s)
- Yusuf C Kaplan
- Terafar - Izmir Katip Celebi University Teratology Information, Training and Research Center, Izmir, Turkey; Izmir Katip Celebi University School of Medicine, Department of Pharmacology, Izmir, Turkey.
| | - Elif Keskin-Arslan
- Terafar - Izmir Katip Celebi University Teratology Information, Training and Research Center, Izmir, Turkey; Izmir Katip Celebi University School of Medicine, Department of Pharmacology, Izmir, Turkey
| | - Gözde Küçüksolak
- Terafar - Izmir Katip Celebi University Teratology Information, Training and Research Center, Izmir, Turkey
| | - Fatih Akyol
- Terafar - Izmir Katip Celebi University Teratology Information, Training and Research Center, Izmir, Turkey
| | - Barış Karadas
- Terafar - Izmir Katip Celebi University Teratology Information, Training and Research Center, Izmir, Turkey; Izmir Katip Celebi University School of Medicine, Department of Pharmacology, Izmir, Turkey
| | - Sacit Nuri Görgel
- Izmir Katip Celebi University School of Medicine, Department of Urology, Izmir, Turkey
| | - Tijen Kaya-Temiz
- Terafar - Izmir Katip Celebi University Teratology Information, Training and Research Center, Izmir, Turkey; Izmir Katip Celebi University School of Medicine, Department of Pharmacology, Izmir, Turkey
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Genome-wide linkage and association study implicates the 10q26 region as a major genetic contributor to primary nonsyndromic vesicoureteric reflux. Sci Rep 2017; 7:14595. [PMID: 29097723 PMCID: PMC5668427 DOI: 10.1038/s41598-017-15062-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 10/06/2017] [Indexed: 12/29/2022] Open
Abstract
Vesicoureteric reflux (VUR) is the commonest urological anomaly in children. Despite treatment improvements, associated renal lesions – congenital dysplasia, acquired scarring or both – are a common cause of childhood hypertension and renal failure. Primary VUR is familial, with transmission rate and sibling risk both approaching 50%, and appears highly genetically heterogeneous. It is often associated with other developmental anomalies of the urinary tract, emphasising its etiology as a disorder of urogenital tract development. We conducted a genome-wide linkage and association study in three European populations to search for loci predisposing to VUR. Family-based association analysis of 1098 parent-affected-child trios and case/control association analysis of 1147 cases and 3789 controls did not reveal any compelling associations, but parametric linkage analysis of 460 families (1062 affected individuals) under a dominant model identified a single region, on 10q26, that showed strong linkage (HLOD = 4.90; ZLRLOD = 4.39) to VUR. The ~9Mb region contains 69 genes, including some good biological candidates. Resequencing this region in selected individuals did not clearly implicate any gene but FOXI2, FANK1 and GLRX3 remain candidates for further investigation. This, the largest genetic study of VUR to date, highlights the 10q26 region as a major genetic contributor to VUR in European populations.
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Modulation of apoptotic response by LAR family phosphatases-cIAP1 signaling during urinary tract morphogenesis. Proc Natl Acad Sci U S A 2017; 114:E9016-E9025. [PMID: 29073098 DOI: 10.1073/pnas.1707229114] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
The elimination of unwanted cells by apoptosis is necessary for tissue morphogenesis. However, the cellular control of morphogenetic apoptosis is poorly understood, notably the modulation of cell sensitivity to apoptotic stimuli. Ureter maturation, the process by which the ureter is displaced to the bladder wall, represents an exquisite example of morphogenetic apoptosis, requiring the receptor protein tyrosine phosphatases (RPTPs): LAR and RPTPσ. Here we show that LAR-RPTPs act through cellular inhibitor of apoptosis protein 1 (cIAP1) to modulate caspase 3,7-mediated ureter maturation. Pharmacologic or genetic inactivation of cIAP1 reverts the apoptotic deficit of LAR-RPTP-deficient embryos. Moreover, Birc2 (cIAP1) inactivation generates excessive apoptosis leading to vesicoureteral reflux in newborns, which underscores the importance of apoptotic modulation during urinary tract morphogenesis. We finally demonstrate that LAR-RPTP deficiency increases cIAP1 stability during apoptotic cell death. Together these results identify a mode of cIAP1 regulation playing a critical role in the cellular response to apoptotic pathway activation in the embryo.
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Iqbal S, Raiz I, Faiz I. Bilateral Hydroureteronephrosis with a Hypertrophied, Trabeculated Urinary Bladder. Malays J Med Sci 2017; 24:106-115. [PMID: 28894411 DOI: 10.21315/mjms2017.24.2.14] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 08/02/2016] [Indexed: 10/19/2022] Open
Abstract
Bilateral hydroureteronephrosis involves the dilatation of the renal pelvis, calyces and ureter; it develops secondary to urinary tract obstruction and leads to a build-up of back pressure in the urinary tract, and it may lead to impairment of renal function and ultimately culminate in renal failure. Although clinically silent in most cases, it can be diagnosed as an incidental finding during evaluation of an unrelated cause. In a minority of patients, it presents with signs and symptoms. Renal calculus is the most common cause, but there are multiple non-calculus aetiologies, and they depend on age and sex. Pelviureteric junction obstruction, benign prostatic hypertrophy, urethral stricture, neurogenic bladder, retroperitoneal mass and bladder outlet obstruction are some of the frequent causes of hydroureteronephrosis in adults. The incidence of non-calculus hydronephrosis is more common in males than in females. Ultrasonography is the most important baseline investigation in the evaluation of patients with hydronephrosis. Here, we report a rarely seen case of bilateral hydroureteronephrosis associated with a hypertrophied, trabeculated bladder in an adult male cadaver, suspected to be due to a primary bladder neck obstruction, and analyse its various other causes, clinical presentations and outcomes.
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Affiliation(s)
- Showkathali Iqbal
- Amala Institute of Medical Sciences, Amala Nagar; Thrissur - 680555, Kerala, India
| | - Iqbal Raiz
- Government Medical College, Kozhikode, Kerala, India
| | - Iqbal Faiz
- Madras Medical College, Chennai, Tamil Nadu, India
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