Search Results (145)

Histopathological staining remains the fibrosis diagnostic gold standard yet suffers from staining artifacts and variability. Nonlinear optical techniques (e.g., spontaneous fluorescence, Second Harmonic Generation) enhance accuracy but struggle with rapid trace-level detection of fibrosis. To address these limitations, a dual-channel nonlinear optical imaging system with excitation wavelengths at 780 nm and 820 nm was developed, enabling simultaneous spontaneous fluorescence and second-harmonic generation imaging through grid localization. This study applies dual-modality nonlinear imaging to achieve label-free, high-resolution visualization of pulmonary and renal fibrosis at the ECM microstructure scale. Through leveraging this system, it is demonstrated that collagen can be rapidly detected via spontaneous fluorescence at 780 nm, whereas the spatial distribution of collagen fibrils is precisely mapped using Second Harmonic Generation at 820 nm. This approach allows for the rapid and sensitive detection of trace fibrosis in a 5-day unilateral ureteral obstruction mouse model. Additionally, we identify that the elastic fibers, which can also be visualized, provide a foundation for staging diagnosis and delivering accurate and quantitative data for pathological studies and analysis. The research findings underscore the potential of this dual-channel nonlinear optical imaging system as a powerful tool for rapid, precise, and noninvasive fibrosis detection and staging. Full article

The use of ileum for ureteral reconstruction was first described in 1906. Since then, its utilization has evolved considerably. Early in the history of ileal ureters, urologists were limited by a lack of familiarity with bowel harvesting and handling. The popularization of ileal conduits for urinary diversions, however, allowed urologists to familiarize themselves with the use of ileum and paved the way for broader applications. With the emergence of laparoscopy and, later, robotic-assisted surgery, the application of ileal ureteral replacement expanded the capabilities of reconstructive urologists. This article describes the historical development of surgical techniques for ileal ureter replacement and the integration of new technologies aiding in improved outcomes, and anticipates potential future directions. In contemporary practice, robotic-assisted ileal ureteral replacement is used in cases of extensive ureteral obstruction or damage. Advantages of the robotic platform include reduced blood loss, shorter recovery time and hospital length of stay, and superior operative ergonomics. Although robotic ileal ureter replacement is a complex and challenging surgery with notable complications, studies have demonstrated the efficacy and safety of this technique in patients with an otherwise end-stage ureter. In addition, the robotic approach has provided urologists the ability to conduct complex reconstructive surgeries including bilateral ureteral replacement in conjunction with bladder augmentation or a urinary diversion. Long-term studies and continued innovation are necessary to further improve the surgical techniques, outcomes, and scope of ileal ureter reconstruction. Full article

Background: Chronic kidney disease (CKD) is a global health problem marked by a persistent deterioration in the function of the nephrons and kidneys. To identify novel therapies for CKD, we investigated the molecular targets associated with the initiation and progression of the disease. Methods: The transcriptional profile dataset of GSE42303 was downloaded from GEO (The Gene Expression Omnibus). Utilizing the R package limma, the differentially expressed genes (DEGs) were identified between control (Con) and unilateral ureteral obstruction (UUO) mice. Then, functional enrichment, protein–protein interactions (PPI) and subsequent hub genes were identified by multiple bioinformatics approaches. Further validations of these hub genes were confirmed through the GSE118339 dataset and in vivo experiments. Results: We found 381 DEGs between Con and UUO mice (308 up-regulated genes and 73 down-regulated genes). GO functions and pathway analysis indicated that DEGs were mainly enriched in activities associated with inflammation and fibrosis. The mRNA expressions of nine hub genes were identified and confirmed by dataset GSE118339 and in vivo experiments. Conclusions: The hub genes Fgg, Penk, Ckap4, and Gpc3 may be new prospective targets for the treatment of the initiation and progression of CKD. Full article

In chronic kidney disease (CKD) research, animal models such as the unilateral ureteral obstruction (UUO) rodent model are crucial to understanding disease progression, particularly renal fibrosis. Despite its widespread use, the molecular mechanisms driving CKD remain incompletely understood. Given the interplay between metabolism and fibrosis, a comprehensive metabolomic analysis of UUO renal tissue is necessary. This study involved untargeted multiplatform analysis using liquid chromatography (LC), gas chromatography (GC), and capillary electrophoresis (CE) coupled with mass spectrometry (MS) to examine murine kidney tissue from the UUO model. The results highlight metabolic changes associated with tubulointerstitial fibrosis, which affect pathways such as the tricarboxylic acid (TCA) cycle, the urea cycle, and lipid metabolism. In particular, fibrosis impacts the lipidomic profile, with decreases in most lipid classes and increases in specific glycerophospholipids, hexosylceramides, and cholesterol esters. These findings demonstrate the value of a multiplatform approach in elucidating metabolic alterations in CKD, providing information on the underlying molecular mechanisms and paving the way for further research. Full article

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/Objectives: Acute obstructive pyelonephritis caused by ureteral calculi is a severe urological emergency that can rapidly progress to life-threatening complications, including urosepsis. Early risk stratification is critical for timely intervention and improved patient outcomes. Although Hu’s nomogram has been proposed as a predictive tool for urosepsis, its external validation remains limited. This study aims to validate Hu’s nomogram in an independent cohort and identify novel clinical and imaging predictors of urosepsis. Methods: This retrospective cohort study included 341 patients diagnosed with ureteral calculi who underwent surgical intervention at a single institution between January 2019 and October 2023. Clinical, laboratory, and imaging data were collected. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of urosepsis. The predictive accuracy of Hu’s nomogram was evaluated using receiver operating characteristic curve analysis. Results: Among 341 patients, 66 (19.4%) developed urosepsis. Multivariate analysis identified female gender, corticosteroid use, lower platelet count, elevated C-reactive protein levels, positive urine white blood cell count, lower computed tomography attenuation values of calculi, and higher computed tomography attenuation values of hydronephrosis as independent predictors of urosepsis. Hu’s nomogram demonstrated a strong predictive performance (area under the curve: 0.761; 95% CI: 0.701–0.821), reaffirming its clinical utility for risk stratification. Conclusions: This study provides an external validation of Hu’s nomogram and identifies novel risk factors for urosepsis prediction, including corticosteroid use and imaging-based parameters. Incorporating these findings into clinical practice may enhance early risk stratification, facilitate timely interventions, and ultimately improve patient outcomes. Full article

Cisplatin is a highly cytotoxic drug used for the treatment of head, neck, and soft tissue cancers; however, it has nephrotoxic effects that can lead to acute kidney injury. Protocatechuic acid (PCA) is a natural widely available antioxidant found in many fruits such as kiwi, mango, and berries. We have recently shown that PCA reduced renal injury in a mouse model of unilateral ureteral obstruction. The current study aims to investigate the protective effects of PCA in Cisplatin-induced inflammation in vitro in Boston University Mouse Proximal Tubular (BUMPT) cells. BUMPT cells were cultured in complete DMEM. Confluent BUMPT cells were then treated with 20 μM Cisplatin ± PCA 50 or 100 μM for 24 h. PCA treatment showed a dose-depending increase in % cell viability in Cisplatin-treated BUMPT cells. PCA treatment also dose-dependently decreased Cisplatin-induced increases in oxidative stress (ROS and TBARS), inflammation (p-NF-κB and IL-6), and apoptosis (cleaved caspase-3 and % of TUNEL⁺ cells) compared to Cisplatin-only treatment. The reduction in oxidative stress, inflammation, and apoptosis with PCA treatment in Cisplatin-treated BUMPT cells was associated with decreases in tubular physical barrier resistance and the expression of the tight junction protein zonula occludens-1 (ZO-1) when compared to BUMPT cells treated with Cisplatin alone. The current findings suggest that PCA treatment improves tubular barrier function in Cisplatin-treated BUMPT cells via reductions in oxidative stress, inflammation, and apoptosis. Full article

Iatrogenic ureteral strictures are uncommon but challenging to manage. We present our expertise in laparoscopic and robot-assisted laparoscopic ureteroureterostomy (LUU and RAUU) for lumbar and iliac strictures and laparoscopic ureteral reimplantation for pelvic strictures. A descriptive study was conducted on nine adult patients who underwent minimally invasive procedures. Six had lumbar or iliac ureteral strictures—five due to ureterorenoscopy and one following pancreaticoduodenectomy for pancreatic cancer. Three developed pelvic strictures after ureterorenoscopy. Preoperative evaluation included a medical history review, abdominal ultrasound, and CT scan. Success was characterized by the absence of symptoms and the lack of obstruction on follow-up imaging at one year. All procedures were technically feasible, with a median operating time of 105 min and a median hospital stay of four days. No major complications occurred. One patient experienced ureteral stricture recurrence following a laparoscopic approach for a lumbar stricture, and required a permanent double-J stent. At a median follow-up of 38 months, 88.88% of patients remained asymptomatic with preserved renal function. Our findings suggest that robotic and laparoscopic ureteral reconstruction performed by experienced surgeons at a tertiary center is a safe and effective option with a low complication rate. Full article

Background/Objectives: Primary obstructive megaureter (POM) is a rare congenital urological condition usually diagnosed prenatally or in early childhood. Conservative management is increasingly preferred due to a high potential for spontaneous resolution. However, reliable predictors of spontaneous resolution remain controversial, complicating clinical decision-making. This study aimed to identify the demographic, clinical, and imaging parameters predictive of spontaneous resolution in patients with primary obstructive megaureter. Methods: We retrospectively analyzed 21 pediatric patients diagnosed with primary obstructive megaureter, who were treated conservatively at the Maria Sklodowska Curie Emergency Clinical Hospital for Children from January 2015 to December 2024. Clinical parameters, imaging findings, and renal function were evaluated. Statistical analyses included univariate comparisons and multivariate logistic regression modeling. Results: Spontaneous resolution occurred in 12 (57%) patients, at a median age of 45.75 months. The only statistically significant predictor identified was the initial hydronephrosis grade (p = 0.046). Patients with mild-to-moderate dilation (Grades I–II) had a significantly higher resolution rate (11 of 15 cases) compared with those with severe dilation (1 of 6 cases). Ureteral diameter showed a trend toward predicting outcomes, with unresolved cases having larger median diameters (15 mm vs. 10.5 mm, p ≈ 0.08). Age at diagnosis, sex, bilateral involvement, and history of urinary infections did not significantly influence resolution rates. Conclusions: The initial severity of hydronephrosis significantly predicts spontaneous resolution in primary obstructive megaureter. Conservative management is particularly justified in mild-to-moderate cases, whereas patients with severe dilation may require early intervention due to lower resolution likelihood. Full article

Background and Objectives: Congenital urological malformations are among the most frequent causes of pediatric chronic kidney disease. Endoscopic balloon dilation and ureteral stenting can be considered less invasive options compared to conventional surgery for primary obstructive megaureter (POM). Nevertheless, the long-term results and side effects of these methods have not yet been well documented. The purpose of this study is to analyze the effectiveness and safety of the endoscopic treatment of POM in children, with the aim of assisting clinical decision making and improving treatment plans. Materials and Methods: A retrospective longitudinal study was performed at the Pediatric Surgery Department of the “M.S. Curie” Emergency Clinical Hospital for Children in Bucharest between October 2020 and September 2024. Eleven endoscopic interventions were performed in five pediatric patients (four boys and one girl) who had six affected ureters, with a median age of 22 months. The inclusion criteria were retrovesical ureter dilation > 7 mm and no prior surgeries of the ureterovesical junction. Cases with secondary megaureters were excluded from the study. The procedures comprised HPEBD and temporary double-J (DJ) stent placement, with systematic postoperative monitoring. Success was defined as improvements in symptoms, a decrease in hydronephrosis, and the preservation of renal function. Results: A final success rate of 83.3% was achieved with endoscopic treatment. Complications were noted in 73% of cases: Clavien–Dindo Grade I (30%); Clavien–Dindo Grade II (20%); Clavien–Dindo Grade IIIb (50%). The documented complications consisted of balloon rupture, stent migration, restenosis, and febrile urinary tract infections (UTIs). Nonetheless, no major complications were observed. The postoperative monitoring showed that renal function was stable and that hydronephrosis had improved gradually. Conclusions: Endoscopic procedures offer a promising, minimally invasive treatment for POM in children with a good success rate. However, the high complication risk necessitates careful patient selection, post-surgery monitoring, and clear guidelines. Full article

Obstructive nephropathy (ON), characterized by urine flow disruption, can induce chronic kidney disease (CKD). Although the release of the obstruction is performed as the primary intervention, renal pathology often persists and progresses. Accordingly, the murine model of releasing unilateral ureteral obstruction (RUUO) is valuable for investigating the molecular events underlying renal damage after obstruction release. Remarkably, after RUUO, disturbances such as oxidative stress, inflammation, lipid accumulation, and fibrosis continue to increase. Mitochondrial dysfunction contributes to fibrosis in the UUO model, but its role in RUUO remains unclear. Additionally, the impact of using antioxidants to restore mitochondrial function and prevent renal fibrosis in RUUO has not been determined. This study aimed to determine the therapeutic effect of pre-administering the antioxidant sulforaphane (SFN) in the RUUO model. SFN was administered 1 day before RUUO to evaluate mitochondrial biogenesis, fatty acids (FA) metabolism, bioenergetics, dynamics, and mitophagy/autophagy mechanisms in the kidney. Our data demonstrated that SFN enhanced mitochondrial biogenesis and reestablished mitochondrial oxygen consumption and β-oxidation. These effects collectively reduced lipid accumulation and normalized mitochondrial dynamics, mitophagy, and autophagy, thereby mitigating fibrosis after obstruction. Our findings suggest that SFN holds promise as a potential therapeutic agent in ON-induced CKD progression in RUUO and opens new avenues in studying antioxidant molecules to treat this disease. Full article

Background and Objectives: This study evaluated the safety and efficacy of long-term indwelling self-expandable covered metallic stents (UVENTA; Taewoong Medical Co., Ltd., Seoul, Republic of Korea) used to manage benign and malignant ureteral strictures. Materials and Methods: We retrospectively identified and analyzed the medical records of all patients who underwent metallic stent insertion at our institution since September 2012. Additionally, we evaluated the technical and clinical success rates and complications of patients who underwent follow-up for more than 36 months. Results: A total of 25 patients underwent metallic stent insertion for ureteral obstructions at our institution. Among them, 18 underwent follow-up for more than 36 months. A total of 21 ureters (15 unilateral and 3 bilateral) were ultimately included in this study. Metallic stents were successfully placed in all ureters using a retrograde approach, with a technical success rate of 100%. The mean follow-up duration was 58.6 months (range, 36–107 months). However, the clinical success rates were 85.7% (18/21 ureters) by 12 months, 61.9% (14/21 ureters) by 24 months, and 52.4% (11/21 ureters) after 36 months. During follow-up, obstructions could not be resolved using metallic stents in eleven ureters (median time to failure, 18.4 months; range, 2−40 months); therefore, they were treated with nephrectomy (three ureters because of a nonfunctional kidney) or percutaneous nephrostomy and double J stent placement (four ureters). Major complications included the encrustation of the metallic stent, flank pain, and gross hematuria. A uretero-enteric fistula occurred in one ureter. In two patients, existing metallic stents were removed and patency was maintained. In another two patients, new metallic stents were inserted without complications. Conclusions: Benign and malignant ureteral obstructions may be treated effectively and safely with metallic stents. However, the patency rate drastically decreased and major complications occurred during long-term follow-up. Therefore, careful patient selection is necessary to achieve better results. Full article

Chronic kidney disease (CKD) progresses through mechanisms involving inflammation, fibrosis, and oxidative stress, leading to the gradual structural and functional deterioration of the kidneys. Tormentic acid (TA), a triterpenoid compound with known anti-inflammatory and antioxidant properties, shows significant potential in counteracting these pathological processes. This study explored the protective role of TA in a unilateral ureteral obstruction (UUO)-induced CKD model. Mice received TA through intraperitoneal injections at a dosage of 5 mg/kg per day for 8 consecutive days, commencing a day before the UUO procedure. The TA treatment significantly improved both structural and functional kidney injury. It suppressed cytokine expression and reduced immune cell infiltration, inhibited the activation of the mitogen-activated protein kinase cascade, and alleviated endoplasmic reticulum stress. Moreover, TA displayed potent anti-fibrotic effects by reversing epithelial-to-mesenchymal transition and inhibiting Smad2/3 activation, reducing extracellular matrix deposition. TA also mitigated oxidative stress by attenuating lipid peroxidation and boosting antioxidant defenses. Additionally, it inhibited apoptosis and ferroptosis by reducing oxidative stress and modulating key cell death markers. Collectively, these findings indicate that TA provides comprehensive renoprotection in the UUO model by effectively targeting inflammation, fibrosis, oxidative stress, and tubular cell death in CKD progression. Full article

Background and Objectives: Double-J stents are urinary catheters that are frequently used in urology. They are now also used in other specialist areas such as obstetrics and gynecology. However, the use of double-J stents is not without side effects. The aim of this review was to highlight the indications and possible adverse effects of the use of these stents in obstetrics and gynecology. Materials and Methods: We analyzed works published after 1995 in the PUBMED, SCOPUS, and Web of Science databases related to the use of double-J stents in obstetrics and gynecology, as well as reported adverse events. We carried out a narrative review of the available literature on this topic. Results: We identified 69 relevant publications that we included in the review. In obstetrics, indications include the treatment of gestational hydronephrosis, some urological conditions during pregnancy, such as obstructive urinary calculi, with or without superinfection, or intraoperative use for cesarean section or hysterectomy after cesarean section, to protect from, or to solve, ureteral lesions. In gynecology, they are used preoperatively or intraoperatively to protect the ureter during gynecological operations in the pelvic area or postoperatively to repair some ureteral injuries. They are also indicated for ureteral obstructions that occur after pelvic radiotherapy for gynecological neoplasms. Complications associated with the use of double-J stents include more frequent urinary tract infections, lower urinary tract symptoms, calcifications and misplacements. Conclusions: Double-J stents are widely used in obstetrics and gynecology and are characterized by good efficiency and safety, although some side effects may occur (lower urinary tract symptoms, hematuria, complications in birth outcomes), which do not limit their use. Summary of evidence: In this review, we analyzed the indications and complications of double-J ureteral stenting in obstetric and gynecologic patients. We found that the procedure is safe, both in the treatment of ureteral obstruction and in the resolution of postoperative complications. No serious complications of ureteral stenting have been noted that would constitute a contraindication to its use. Future prospective studies in large patient cohorts are necessary to validate our data. Full article

Kidney fibrosis is the common pathological pathway in progressive chronic kidney disease (CKD), and current treatments are largely ineffective. The C-X-C chemokine receptor 4 (CXCR4) is crucial to fibrosis development. By using neural cell adhesion molecules as scaffolds with binding loops that mimic the shape of shark antibodies, fully humanized single-domain i-bodies have been developed. The first-generation i-body, AD-114, demonstrated antifibrotic effects in a mouse model of folic acid (FA)-induced renal fibrosis. The second-generation i-body, AD-214, is an Fc-fusion protein with an extended half-life, enhanced activity, and a mutated Fc domain to prevent immune activation. To investigate the renoprotective mechanisms of AD-214, RPTEC/TERT1 cells (a human proximal tubular cell line) were incubated with TGF-b1 with/without AD-214 and the supernatant was collected to measure collagen levels by Western blot. Mice with unilateral ureteral obstruction (UUO) received AD-214 intraperitoneally (i.p.) every two days for 14 days. Kidney fibrosis markers and kidney function were then analyzed. AD-214 suppressed TGF-b1-induced collagen overexpression in RPTEC/TERT1 cells. In UUO mice, AD-214 reduced extracellular matrix (ECM) deposition, restored kidney function, and limited leukocyte infiltration. In a scratch assay, AD-214 also inhibited macrophage migration. To conclude, i-body AD-214 attenuates UUO-induced kidney fibrosis by inhibiting leukocyte infiltration and macrophage migration. Full article