The Intrarenal Reflux Diagnosed by Contrast-Enhanced Voiding Urosonography (ceVUS): A Reason for the Reclassification of Vesicoureteral Reflux and New Therapeutic Approach?

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).

Mouse and human studies support DSTYK loss of function as a low-penetrance and variable expressivity risk factor for congenital urinary tract anomalies.

Purpose: Previous work identified rare variants in DSTYK associated with human congenital anomalies of the kidney and urinary tract (CAKUT). Here, we present a series of mouse and human studies to clarify the association, penetrance, and expressivity of DSTYK variants.

Methods: We phenotypically characterized Dstyk knockout mice of 3 separate inbred backgrounds and re-analyzed the original family segregating the DSTYK c.

Bardet-Biedl syndrome caused by compound heterozygosity in BBS12 gene: a case report of one family with three affected members.

Introduction: Bardet-Biedl syndrome (BBS) is a rare genetic syndrome caused by a mutation in one of 26 different genes responsible for normal structure and/or function of primary cilia. The syndrome is characterized by multiorgan involvement with gradual onset of occurrence of clinical signs and symptoms resulting in great phenotypic variability and what is more important, often difficulties with establishing the timely diagnosis.

Case Report: We report a case of a one family with three members with BBS caused by a very rare mutation, a compound heterozygosity in gene.

Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome.

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown.

Rare Single Nucleotide and Copy Number Variants and the Etiology of Congenital Obstructive Uropathy: Implications for Genetic Diagnosis.

Significance Statement: Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.

The Spectrum of Parenchymal Changes in Kidneys Affected by Intrarenal Reflux, Diagnosed by Contrast-Enhanced Voiding Urosonography and DMSA Scan.

Purpose: To describe the parenchymal defects in kidneys with intrarenal reflux (IRR) diagnosed using contrast-enhanced voiding urosonography (ceVUS) and Tc-DMSA scintigraphy (DMSA scan).

Materials And Methods: A group of 186 uretero-renal units (URUs) was analyzed using ceVUS and DMSA scans: 47 without vesicoureteral reflux (VUR) (group A) and 139 with VURs, comprising 73 VURs without (group B), and 66 with IRR (group C). VURs included non-dilating (grades I-II), mildly non-dilating (grade III), and non-dilating (grades IV-V) grades.

Differences in Immunohistochemical and Ultrastructural Features between Podocytes and Parietal Epithelial Cells (PECs) Are Observed in Developing, Healthy Postnatal, and Pathologically Changed Human Kidneys.

During human kidney development, cells of the proximal nephron gradually differentiate into podocytes and parietal epithelial cells (PECs). Podocytes are terminally differentiated cells that play a key role in both normal and pathological kidney function. Therefore, the potential of podocytes to regenerate or be replaced by other cell populations (PECs) is of great interest for the possible treatment of kidney diseases.

Clinical and histopathological characteristics of COL4A3 c.2881+1G>A variant causing Alport spectrum disorders in Croatian population.

Alport syndrome (AS) and thin basement membrane nephropathy (TBMN) are part of the spectrum of kidney disorders caused by pathogenic variants in α3, α4, or α5 chains of the collagen type IV, the major structural component of the glomerular basement membrane (GBM). Using targeted next-generation sequencing (NGS), 34 AS/TBMN patients (58.8% male) from 12 unrelated families were found positive for heterozygous c.

A Remote Questionnaire-Based Study to Compare Alcohol Use in 1030 Final-Year High School Students in Split-Dalmatia County, Croatia Before and During the National Lockdown Due to the COVID-19 Pandemic.

BACKGROUND The COVID-19 pandemic affected drinking behaviors among adolescents. This remote questionnaire-based study aimed to compare alcohol use in 1030 final-year high school students in Split-Dalmatia County (SDC), Croatia before and during the national lockdown due to the COVID-19 pandemic. MATERIAL AND METHODS An online self-reported questionnaire survey was conducted among 1030 final-year high school students (57.

Expression of renal vitamin D receptors and metabolizing enzymes in IgA nephropathy.

Aim: One of the main causes of end-stage renal disease (ESRD) in the world is IgA nephropathy (IgAN). Since kidney is a key player in vitamin D metabolism, we investigated the expression of renal vitamin D receptors (VDR) and metabolizing enzymes in IgA nephropathy patients (IgAN-P).

Methods: The sample included twelve IgAN-P who underwent ultrasound-guided renal biopsies and five controls who underwent nephrectomy due to clear renal carcinoma.

Laser-puncture of the ureterocele in neonatal patients significantly decreases an incidence of de novo vesico-ureteral reflux than electrosurgical incision.

Introduction: Endoscopic laser-puncture or electrosurgical incision are the most commonly used minimaly invasive approaches for the treatment of the ureterocele. Both techniques are mainly successful in decompressing of ureteroceles, but the consequence of such treatment may be formation of de novo vesicoureteral reflux and febrile urinary tract infection which could impact the final results.

Objective: To compare outcomes of treatment of two endoscopic techniques used in management of neonatal patients with intravesical ureterocele.

Intrarenal Reflux in the Light of Contrast-Enhanced Voiding Urosonography.

The aim of this study was to analyze the incidence of intrarenal reflux (IRR) among vesicoureteral refluxes (VURs), diagnosed by contrast-enhanced voiding urosonography (ceVUS), to define VURs which are positive to IRR and their locations in the kidney. Seventy patients with VURs, including 103 uretero-renal units (URUs) with VURs of grades II-V (37 URUs were excluded because of renal anomalies or absence of VUR) were examined with ceVUS due to recurrent febrile UTI or first febrile UTI accompanied by abnormalities on renal ultrasonography. Patients were examined on GE Logiq S8 ultrasound machine, using second generation of ultrasound contrast agent.

Types of Parenchymal Changes Diagnosed on DMSA Scans of Kidneys Affected by Different Grades of Vesicoureteral Reflux.

BACKGROUND Renal parenchymal damage and scarring usually is associated with urinary tract infection (UTI), whereas the impact of vesicoureteral reflux (VUR) on the kidneys is unclear. We aimed to compare kidneys with all grades of VUR (grades Io-V) and those without VUR by using direct radionuclide cystography, voiding cystourethrography, and findings from 99mTc-DMSA scintigraphy (DMSA scan). MATERIAL AND METHODS The present analysis included 253 renal ureteral units (RUU) from 129 children with VUR and recurrent UTI and children with a single febrile UTI associated with abnormal ultrasonographic findings.

Copy Number Variant Analysis and Genome-wide Association Study Identify Loci with Large Effect for Vesicoureteral Reflux.

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.

Connexin Signaling in the Juxtaglomerular Apparatus (JGA) of Developing, Postnatal Healthy and Nephrotic Human Kidneys.

Our study analyzed the expression pattern of different connexins (Cxs) and renin positive cells in the juxtaglomerular apparatus (JGA) of developing, postnatal healthy human kidneys and in nephrotic syndrome of the Finnish type (CNF), by using double immunofluorescence, electron microscopy and statistical measuring. The JGA contained several cell types connected by Cxs, and consisting of macula densa, extraglomerular mesangium (EM) and juxtaglomerular cells (JC), which release renin involved in renin-angiotensin- aldosteron system (RAS) of arterial blood pressure control. During JGA development, strong Cx40 expression gradually decreased, while expression of Cx37, Cx43 and Cx45 increased, postnatally showing more equalized expression patterning.

Spatio-temporal patterning of different connexins in developing and postnatal human kidneys and in nephrotic syndrome of the Finnish type (CNF).

Connexins (Cxs) are membrane-spanning proteins which enable flow of information important for kidney homeostasis. Changes in their spatiotemporal patterning characterize blood vessel abnormalities and chronic kidney diseases (CKD). We analysed spatiotemporal expression of Cx37, Cx40, Cx43 and Cx45 in nephron and glomerular cells of developing, postnatal kidneys, and nephrotic syndrome of the Finnish type (CNF) by using immunohistochemistry, statistical methods and electron microscopy.

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

Background: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers.

Methods: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated.

Epidemiology of 10-year paediatric renal biopsies in the region of southern Croatia.

Background: Information about renal diseases in children is available from national registries of renal biopsies. Aim of the study was to compare the clinical presentation of glomerular diseases and tubulointerstitial space diseases with pathohistological diagnosis of indicated renal biopsies from pediatric population in the Croatian region of Dalmatia.

Methods: Out of 231 pediatric patients with suspected glomerular and tubulointerstitial diseases, 54 underwent ultrasound-guided renal biopsy at University Hospital of Split.

Expression and localization of DAB1 and Reelin during normal human kidney development.

Aim: To explore the spatial and temporal expression patterns of DAB1 and Reelin in the developing and postnatal healthy human kidneys as potential determinants of kidney development.

Methods: Paraffin-embedded fetal kidney tissue between the 13/14th and 38th developmental weeks (dw) and postnatal tissue at 1.5 and 7 years were stained with DAB1 and Reelin antibodies by double immunofluorescence.

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy.

Background: Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors.

Immunohistochemical expression pattern of RIP5, FGFR1, FGFR2 and HIP2 in the normal human kidney development.

Aim: Present study analyses the co-localisation of RIP5 with FGFR1, FGFR2 and HIP2 in the developing kidney, as RIP5 is a major determinant of urinary tract development, downstream of FGF-signaling.

Methods: Paraffin embedded human kidney tissues of 16 conceptuses between the 6th-22th developmental week were analysed using double-immunofluorescence method with RIP5/FGFR1/FGFR2 and HIP2 markers. Quantification of positive cells were performed using Kruskal-Wallis test.

Author Correction: The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

In the version of this article initially published, affiliation 38 incorrectly read "ICNU-Nephrology and Urology Department, Barcelona, Spain"; "Renal Division, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain" is the correct affiliation. The error has been corrected in the HTML and PDF versions of the article.

Association of Appendicitis, Helicobacter Pylori Positive Gastritis and Thrombotic Thrombocytopenic Purpura in an Adolescent.

BACKGROUND Thrombotic thrombocytopenic purpura (TTP) in children is a rare life-threatening syndrome, characterized by microangiopathic hemolytic anemia, thrombocytopenia with renal dysfunction, neurologic symptoms, and fever. TTP is usually caused by deficient activity of von Willebrand factor cleaving protease (ADAMTS13), due to either gene mutations or acquired via anti-ADAMTS13 autoantibodies. It can be triggered by bone marrow or solid organ transplantation, cardiothoracic-, abdominal-, and orthopedic surgeries, infections including very rarely Helicobacter pylori infection.

The copy number variation landscape of congenital anomalies of the kidney and urinary tract.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD).