Search Results (10)

Background/Objectives: The human kallikrein-related peptidase 6 (KLK6), a serine protease with trypsin-like properties, belongs to the 15-member kallikrein (KLK) gene family and is predominantly recognized for its role in oncogenesis, neurodegenerative disorders, and skin conditions. Aquaporins (AQPs) are integral membrane proteins that facilitate water transport across cell membranes. AQP1 is constitutively active in the kidneys and plays a crucial role in reabsorbing filtered water, while AQP2 is regulated by vasopressin and is essential for maintaining body fluid homeostasis. The primary objective of the present study is to investigate the spatio-temporal expression patterns of KLK6, AQP1, and AQP2 throughout normal human nephrogenesis and congenital kidney and urinary tract (CAKUT) abnormalities: duplex kidneys, horseshoe kidneys, and dysplastic kidneys. Methods: An immunofluorescence analysis of KLK6, AQP1, and AQP2 was performed on 37 paraffin-embedded fetal kidney samples. The area percentage of KLK6 in the kidney cortex was calculated in normal developing samples during developmental phases 2, 3, and 4 and compared with CAKUT samples. Results: KLK6 exhibits distinct spatiotemporal expression patterns during human kidney development, with consistent localization in proximal tubules. Its subcellular positioning shifts from the basolateral cytoplasm in early phases to the apical cytoplasm in later stages, which may be strategically positioned to act on its substrate in either the peritubular space or the tubular fluid. KLK6 expression followed a quadratic trajectory, peaking at Ph4. This marked increase in the final developmental phase aligns with its strong expression in mature kidneys, suggesting a potential role in proximal tubule differentiation and functional maturation through facilitating extracellular matrix remodeling and activating proteinase-activated receptors, modulating the signaling pathways that are essential for tubular development. In duplex kidneys, structural abnormalities such as ureteral obstruction and hydronephrosis may upregulate KLK6 as part of a reparative response, while its downregulation could impair epithelial remodeling and cytoskeletal integrity, exacerbating dysplastic phenotypes. Conclusions: These findings highlight the potential of KLK6 involvement in normal kidney development and the pathology of CAKUT. Full article

Background: Antenatal hydronephrosis (ANH) is the most common congenital renal and urinary tract anomaly, and parenchymal damage and renal fibrosis due to pathological hydronephrosis are the main causes of end-stage renal disease in children and chronic kidney disease in adults. At present, there is no validated biomarker for ANH, and diagnostic criteria other than prenatal ultrasonography (US) assessment are lacking. Therefore, we assessed to determine if biomarkers extracted from amniotic fluid small extracellular vesicles (sEVs) might be used as ANH diagnosis. Methods: With congenital ureteropelvic junction obstruction (UPJO) as the ultimate diagnosis, 10 pregnant women with Grade III-IV ANH and 10 normal pregnant women were recruited. The sEVs were extracted from amniotic fluid supernatant of all samples. Transcriptomic sequencing of sEVs in the discovery cohort identified the differential expression profiles for ANH. The known differentially expressed lncRNAs (DE-lncRNAs) were assessed by qRT–PCR in the validation cohort. Results: We explored the global RNA expression in sEVs from amniotic fluid. The differential expression profiles of both mRNAs and lncRNAs were related to fetal kidney development. Six known DE-lncRNAs were identified for ANH, and three of those with high expression were verified in more ANH samples. In particular, the upregulated LINC02863 and its target genes were associated with renal development and morphogenesis. The four predicted novel lncRNAs in high expression were also related to mesenchymal morphogenesis and the STAT3 signaling pathway and may play roles in ANH. Conclusions: We identified differentially expressed RNAs of all species in the sEVs from amniotic fluid, and the validated known DE-lncRNAs might serve as promising diagnostic biomarkers for ANH. Full article

The management of ureter hydronephrosis and urolithiasis during pregnancy has been changed by the adoption of ureteric stents. Despite their broad use for several other conditions, from emergency to elective settings, their complications cannot be ignored. Being most prevalent during pregnancy, urinary tract infections and stent encrustations are particularly common and can affect either fetal growth or maternal–fetal homeostasis, leading to obstetric complications. The main concern associated with ureteric stents is the indwelling time, which could represent the potential trigger of those complications. However, to ensure the optimal management of a ureteric stent during pregnancy, factors such as the grading of encrustations and the presence, size, and location of stones should be evaluated in pre-operative planning. As a consequence, a multimodal approach, including obstetrics, gynecologists, urologists, and nurses, is essential to ensure a complication-free procedure and successful ureteric stent removal. Finally, future research should focus on utilizing biodegradable and biocompatible materials to reduce and even eliminate the complications related to forgotten stents in order to reduce the financial burden associated with stent replacement and the management of stent-encrustation-related complications. Full article

(1) Background: To examine the incidence of the prenatal diagnosis of the renal double-collecting system (rDCS) and describe its clinical outcome and associated genetic abnormalities. (2) Methods: This retrospective study included women who attended the obstetric clinic for early fetal anatomic sonography with findings of a renal DCS. Diagnosis was conducted by an expert sonographer using defined criteria. (3) Results: In total, 29,268 women underwent early ultrasound anatomical screening at 14–16 weeks, and 383 cases of rDCS were diagnosed (prevalence: 1:76). Associated abnormalities were diagnosed in eleven pregnancies; four had chromosomal aberrations. No chromosomal abnormalities were reported in isolated cases. Ectopic uretrocele and dysplastic kidney were diagnosed in 6 (1.5%) and 5 (1.3%) fetuses, respectively. One girl was diagnosed with vesicoureteral reflux and recurrent UTIs, and two boys were diagnosed with undescended testis. The recurrence rate of rDCS was 8% in subsequent pregnancies. (4) Conclusions: In light of its benign nature, we speculate that isolated rDCS may be considered a benign anatomic variant, but a repeat examination in the third trimester is recommended to assess hydronephrosis. Full article

Background and Objectives: Urosepsis is a significant cause of maternal and fetal mortality. While certain risk factors for urinary tract infections (UTIs) in pregnant women are well established, those associated with an elevated risk of urosepsis in pregnant women with upper UTIs remain less defined. This study aims to identify factors linked to an increased risk of urosepsis and examine urologic treatment outcomes in such cases. Materials and Methods: We conducted a retrospective analysis on 66 pregnant women diagnosed with urosepsis over a nine-year period. A control group included 164 pregnant women with upper UTIs, excluding urosepsis, admitted during the same timeframe. This study highlights factors potentially contributing to urosepsis risk, including comorbidities like anemia, pregnancy-related hydronephrosis or secondary to reno-ureteral lithiasis, prior UTIs, coexisting urological conditions, and urologic procedures. Outcomes of urologic treatments, hospitalization duration, obstetric transfers due to fetal distress, and complications associated with double-J catheters were analyzed. Results: Pregnant women with urosepsis exhibited a higher prevalence of anemia (69.7% vs. 50.0%, p = 0.006), 2nd–3rd grade hydronephrosis (81.8% vs. 52.8%, p = 0.001), and fever over 38 °C (89.4% vs. 42.1%, p = 0.001). They also had a more intense inflammatory syndrome (leukocyte count 18,191 ± 6414 vs. 14,350 ± 3860/mmc, p = 0.001, and C-reactive protein (CRP) 142.70 ± 83.50 vs. 72.76 ± 66.37 mg/dL, p = 0.001) and higher creatinine levels (0.77 ± 0.81 vs. 0.59 ± 0.22, p = 0.017). On multivariate analysis, factors associated with increased risk for urosepsis were anemia (Odds Ratio (OR) 2.622, 95% CI 1.220–5.634), 2nd–3rd grade hydronephrosis (OR 6.581, 95% CI 2.802–15.460), and fever over 38 °C (OR 11.612, 95% CI 4.804–28.07). Regarding outcomes, the urosepsis group had a higher rate of urological maneuvers (87.9% vs. 36%, p = 0.001), a higher rate of obstetric transfers due to fetal distress (22.7% vs. 1.2%, p = 0.001), and migration of double-J catheters (6.1% vs. 0.6%, p = 0.016), but no maternal fatality was encountered. However, they experienced the same rate of total complications related to double-J catheters (19.69% vs. 12.80%, p > 0.05). The pregnant women in both groups had the infection more frequently on the right kidney, were in the second trimester and were nulliparous. Conclusions: Pregnant women at increased risk for urosepsis include those with anemia, hydronephrosis due to gestational, or reno-ureteral lithiasis, and fever over 38 °C. While the prognosis for pregnant women with urosepsis is generally favorable, urological intervention may not prevent a higher incidence of fetal distress and the need for obstetric transfers compared to pregnant women with uncomplicated upper UTIs. Full article

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by the arrest of fetal lung formation, resulting in neonatal death due to acute respiratory failure and pulmonary arterial hypertension. Heterozygous single-nucleotide variants or copy-number variant (CNV) deletions involving the FOXF1 gene and/or its lung-specific enhancer are found in the vast majority of ACDMPV patients. ACDMPV is often accompanied by extrapulmonary malformations, including the gastrointestinal, cardiac, or genitourinary systems. Thus far, most of the described ACDMPV patients have been diagnosed post mortem, based on histologic evaluation of the lung tissue and/or genetic testing. Here, we report a case of a prenatally detected de novo CNV deletion (~0.74 Mb) involving the FOXF1 gene in a fetus with ACDMPV and hydronephrosis. Since ACDMPV is challenging to detect by ultrasound examination, the more widespread implementation of prenatal genetic testing can facilitate early diagnosis, improve appropriate genetic counselling, and further management. Full article

Pyelectasis, also known as renal pelvic dilatation or hydronephrosis, is frequently found on fetal ultrasound. This study correlated prenatally-detected, moderate pyelectasis with postnatal outcomes. This retrospective, observational study was conducted at a tertiary medical center in Israel. The study group consisted of 54 fetuses with prenatal diagnosis of pyelectasis on ultrasound scan during the second trimester, defined as anteroposterior renal pelvic diameter (APRPD) 6–9.9 mm. Long-term postnatal outcomes and renal-related sequelae were obtained using medical records and telephone-based questionnaires. The control group included 98 cases with APRPD < 6 mm. Results indicate that fetal pyelectasis 6–9.9 mm was more frequent among males (68.5%) than females (51%, p = 0.034). We did not find significant correlations between 6–9.9 mm pyelectasis and other anomalies or chromosomal/genetic disorders. Pyelectasis resolved during the pregnancy in 15/54 (27.8%) cases. There was no change in 17/54 (31.5%) and 22/54 (40.7%) progressed to hydronephrosis Among the study group, 25/54 (46.3%) were diagnosed with neonatal hydronephrosis. There were more cases of renal reflux or renal obstruction in the study group compared to the control group 8/54 (14.8%) vs. 1/98 (1.0%), respectively; p = 0.002. In conclusion, most cases of 6–9.9 mm pyelectasis remained stable or resolved spontaneously during pregnancy. There was a higher rate of postnatal renal reflux and renal obstruction in this group; however, most did not require surgical intervention. Full article

A case of severe fetal hydronephrosis due to isolated bilateral stenosis of the pyelo-ureteral junction was diagnosed at our centre. Surprisingly, a negative renal ultrasound scan was performed on the 3rd postnatal day. An ultrasound follow-up showed severe bilateral pyelectasis a few weeks later. The infant underwent bilateral pyeloplasty at six months of age with an excellent outcome. Such a neonatal picture may be due to the reduction of urinary output secondary to excessive postnatal weight loss and dehydration. In this case, prenatal ultrasound result was more reliable than postnatal ultrasound, emphasizing the importance of postnatal urologic follow-up after prenatal indication. Full article

Background: Posterior urethral valves (PUVs) are usually suspected during antenatal sonograms or by postnatal evidence of bilateral hydronephrosis with enlarged bladder. Gross hematuria as an initial manifestation of PUV with a history of normal antenatal sonogram is very rare. Methods: This is a retrospective chart study. Results: We describe a nine-day-old male neonate who presented with gross hematuria and was later found to have a urinary tract infection (UTI) and severe acute kidney injury (AKI). The mother apparently had normal antenatal sonograms with no evidence of fetal hydronephrosis. The child did not have postnatal renal bladder sonogram done until gross hematuria occurred at Day 9 of life. Sonogram showed bilateral severe hydronephrosis and hydroureter with enlarged bladder. The patient underwent ablation of the PUVs after initial bladder decompression with indwelling urethral catheterization. His AKI resolved after prompt treatment of UTI and PUV ablation. Conclusions: This report emphasizes the importance of a high index of suspicion for obstructive uropathy in a newborn with gross hematuria irrespective of prenatal sonogram findings. Full article

Dioxins and related compounds induce morphological abnormalities in developing animals in an aryl hydrocarbon receptor (AhR)-dependent manner. Here we review the studies in which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is used as a prototypical compound to elucidate the pathogenesis of morphological abnormalities. TCDD-induced cleft palate in fetal mice involves a delay in palatogenesis and dissociation of fused palate shelves. TCDD-induced hydronephrosis, once considered to be caused by the anatomical obstruction of the ureter, is now separated into TCDD-induced obstructive and non-obstructive hydronephrosis, which develops during fetal and neonatal periods, respectively. In the latter, a prostaglandin E₂ synthesis pathway and urine concentration system are involved. TCDD-induced abnormal development of prostate involves agenesis of the ventral lobe. A suggested mechanism is that AhR activation in the urogenital sinus mesenchyme by TCDD modulates the wingless-type MMTV integration site family (WNT)/β-catenin signaling cascade to interfere with budding from urogenital sinus epithelium. TCDD exposure to zebrafish embryos induces loss of epicardium progenitor cells and heart malformation. AHR2-dependent downregulation of Sox9b expression in cardiomyocytes is a suggested underlying mechanism. TCDD-induced craniofacial malformation in zebrafish is considered to result from the AHR2-dependent reduction in SRY-box 9b (SOX9b), probably partly via the noncoding RNA slincR, resulting in the underdevelopment of chondrocytes and cartilage. Full article