Myricetin attenuates renal fibrosis by activating Nrf2/HO-1 pathway to inhibit oxidative stress / 药学学报

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL-1) were used to induce fibrotic model, and high glucose (30 mmol·L-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

Effects of obacunone on renal interstitial fibrosis and ferroptosis in unilateral ureteral obstruction model mice / 中国药房

OBJECTVE To study the improvement effects of obacunone on renal interstitial fibrosis （RIF） in unilateral ureteral obstruction （UUO） model mice， and to investigate its mechanism based on ferroptosis mediated by nuclear factor erythroid 2- related factor 2（Nrf2）/glutathione peroxidase 4 （GPx4） signaling pathway. METHODS Thirty mice were randomly divided into sham operation group， model group， irbesartan group （positive control， 20 mg/kg）， obacunone low-dose and high-dose groups （10， 40 mg/kg）， with 6 mice in each group. Except for sham operation group， UUO model was established by ligation of unilateral ureter in other groups. After operation， administration groups were given intraperitoneal injection of relevant medicine， and sham operation group and model group were given intraperitoneal injection of constant volume of normal saline， once a day， for 7 consecutive days. The levels of creatinine （Cr） and blood urea nitrogen （BUN）， the content of malondialdehyde （MDA） and the activities of total superoxide dismutase （T-SOD） in serum and the concentration of Fe2+ in renal tissue were all detected. HE staining and Masson staining were performed to observe the morphology and the fibrosis of renal tissues. Immunohisto- chemical staining was used to determine expressions of the fibronectin （Fn）， α-smooth muscle actin （α-SMA）， GPx4 964083717@qq.com and Nrf2 in renal tissue. Western blot and real-time quantitative polymerase chain reaction （RT-qPCR） were used E-mail：834300205@qq.com to detect the protein and mRNA levels of Fn， α-SMA， Nrf2， GPx4 and SLC7A11 in the renal tissues. RESULTS Compared with sham operation group， serum levels of Cr and BUN， the concentration of Fe2+ in renal tissue， the protein and mRNA levels of Fn and α-SMA in model group were increased significantly （P＜0.05）， while the activity of T-SOD in serum， protein and mRNA expressions of Nrf2， GPx4， SLC7A11 in kidney tissue were significantly decreased （P＜0.05）； in the kidney tissue， the renal tubules were dilated， the collagen deposition was obvious， the fibrous bands were thicker and darker， and the renal interstitial inflammatory cells infiltrated significantly. After intervened with obacunone， the levels of above indexes （except for mRNA expression of SLC7A11 in obacunone low-dose group） in serum and renal tissue were reversed significantly （P＜0.05）， and pathological damage and collagen deposition of kidney tissue were alleviated. CONCLUSIONS Obacunone can improve renal interstitial fibrosis of UUO model mice， the mechanism of which may be associated with activating the Nrf2/GPx4 pathway and then inhibiting ferroptosis to relieve RIF in UUO model mice.

Effect and Mechanism of Baoshen Prescription in Alleviating Renal Fibrosis in UUO Mice by Regulating ERK/p38 MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the protective effect of Baoshen prescription against renal fibrosis and explore its underlying mechanism through network pharmacology， molecular docking， and in vivo experiments. MethodAll mice were randomly divided into sham surgery group， model group， low-， medium-， and high-dose Baoshen prescription groups， and a benazepril hydrochloride group. Unilateral ureteral obstruction （UUO） was performed to establish a renal fibrosis model， and the administration of Baoshen prescription at low， medium， and high doses （0.455， 0.91， and 1.82 g·kg-1）， and benazepril hydrochloride （1.68 mg·kg-1） or distilled water began on the same day as model preparation. Mice in the model group and the sham surgery group were given an equal volume of distilled water. The intervention was carried out once daily for 14 days. Mouse serum levels of blood urea nitrogen （BUN） and creatinine （Cr） were measured. Hematoxylin-eosin （HE） staining and Masson staining were used to observe renal pathological changes. Western blot and immunohistochemistry were used to assess the expression of fibronectin （FN）， α-smooth muscle actin （α-SMA）， and E-cadherin， which are related to renal fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of transforming growth factor-β1 （TGF-β1）， tumor necrosis factor-α （TNF-α）， NOD-like receptor protein 3 （NLRP3）， and monocyte chemoattractant protein-1 （MCP-1） in renal tissues. The mechanism of Baoshen prescription in improving renal fibrosis was explored through network pharmacology， molecular docking， and Western blot experiments. ResultCompared with the sham surgery group， the model group showed significantly increased levels of BUN and Cr （P<0.01）. The model group exhibited abnormal renal glomerular morphology， loss of tubular brush borders， tubular dilation， and an enlarged area of blue collagen fibers. Mice in the model group showed significantly elevated levels of FN and α-SMA （P<0.01）， significantly decreased expression of E-cadherin （P<0.01）， and significantly increased expression of TGF-β1， TNF-α， NLRP3， and MCP-1 mRNA （P<0.05， P<0.01）. Compared with the model group， the Baoshen prescription groups showed significantly reduced BUN and Cr levels （P<0.01）， alleviated renal pathological damage， improved fibrosis， reduced expression of FN and α-SMA （P<0.01）， increased E-cadherin expression （P<0.01）， and downregulated mRNA expression of TGF-β1， TNF-α， NLRP3， and MCP-1 （P<0.05， P<0.01）. Network pharmacology and molecular docking predicted that Baoshen prescription could potentially improve renal fibrosis through the extracellular signal-regulated kinase （ERK）/p38 mitogen-activated protein kinase （MAPK） signaling pathway. Pharmacological research showed that compared with the sham surgery group， the model group exhibited significantly increased expression of phosphorylated （p）-ERK and p-p38 （P<0.05， P<0.01）. Compared with the model group， medium- and high-dose Baoshen prescription groups showed significantly downregulated expression of p-ERK and p-p38 proteins （P<0.05， P<0.01）. ConclusionBaoshen prescription can effectively improve renal fibrosis induced by UUO in mice， and its mechanism of action may be related to the ERK/p38 MAPK signaling pathway.

The efficacy of pedicled bladder muscle flap in the repair and reconstruction of urinary tract obstruction / 中华泌尿外科杂志

Objective:To explore the efficacy of pedicled bladder muscle flap in the repair of urinary tract obstruction.Methods:The data of 26 patients with urinary tract obstruction admitted to Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine from March 2016 to June 2021 were retrospectively reviewed. There were 14 males and 12 females, with the age ranged from 2 to 75 years old. Refractory bladder neck obstruction after prostatic hyperplasia surgery in 12 cases, with the age of (70.0±3.5) years old.They all experienced at least 2 times of transurethral stenosis incisionor resection. Transpubic cystostomy tube was placed in 9 patients. Posttraumatic pelvic fractures lead to bladder neck atresia and urethral injury in 6 girls, with the age of (10.5±2.1) years old. The bladder neck atresia and urethral obliteration length was 1-2 cm determined by urethrography. Eight cases suffered ureteral strictures after gynecological myomectomy or ureteroscopy holmium laser lithotripsy(4 cases of each type), including two males and six females, with the age of (55.0±3.2) years old. The length of ureteral stricture or defect was 5-6 cm determined by intravenous urography(IVU) or CT urography(CTU). The patients with bladder neck obstruction underwent the following surgery: The "Y" incision of the bladder and stenosis of the prostate urethra was performed and the pedicled bladder muscle flap was inserted into the normal urethral mucosa to complete the Y-V plasty. In the 6 girl patients, pedicled bladder muscle flap(2-4 cm) augmented reconstruction were performed. All above 18 patients, whose urethral catheter was indwelled for 3-4 weeks, urinary flow rate and urethroscopy examination were performed to evaluate the effect of surgery 4 weeks and 3 months after the operation. As the 8 cases with ureteral strictures, the pedicled bladder muscle flap (7-8 cm) ureteroplasty was performed and the ureteral stent was retained for 4 weeks. Ultrasonography and IVU/CTU were performed 4 weeks and 3 months postoperatively. The patency of the ureteral lumen and whether it is accompanied by hydronephrosis, lower back pain, and urinary tract infection were assessed.Results:All patients underwent pedicled bladder muscle flap reconstructive surgery successfully and no serious complications occurred postoperatively. The patients were followed up for (8.2± 2.2) months. As urethral catheters were removed, 10 patients with refractory neck obstruction could return to normal urination with the urinary flow Q max (17.2±2.8)ml/s, while 2 patient had dysuria and were treated with regular urethral dilatation. The catheter was removed 4 weeks after the reconstructive surgery in 6 girls with bladder neck atresia and urethral injury after posttraumatic pelvic fracture. Five could successfully urinate with the urinary flow Q max of (16.7±1.1)ml/s, and one girl had urinary incontinence, waiting for further operation.The ureteral stent was removed after ureteroplasty in 8 patients. CTU and IVU examination showed no ureters with obstruction.No one had low back pain, discomfort, or urinary tract infection. Conclusions:The reconstruction using the pedicled bladder muscle flap was a convenient, minimally invasive and effective technique for the management of adjacent lower ureters, bladder neck, and proximal urethra.

Effect of Liuwei Dihuang decoction on β-catenin and EMT in kidney tissue of UUO rats / 中国药理学通报

Aim To explore the effect of Liuwei Dihuang decoction ( LWDHD) on the expression of β-catenin, E-cadherin,α-SMA, the pathological changes of renal tissue, and the changes of an epithelial-mesen-chymal transformation ( EMT) in renal tissue of rats with unilateral ureteral obstruction ( UUO ) . Methods Forty-eight SPF grade SD rats were randomly divided into sham group ( Sham), model group ( UUO), Liuwei Dihuang decoction low, medium, and high groups ( LWDHD 3. 375, 6. 75, 13. 5 g · kg

Multicenter comparative study of open, laparoscopic, and robotic pyeloplasty in the pediatric population for the treatment of ureteropelvic junction obstruction (UPJO)

ABSTRACT Introduction: Dismembered open pyeloplasty described by Anderson and Hynes is the "gold standard" for the treatment of ureteropelvic junction obstruction. The aim of our study was to compare the results of open (OP) vs laparoscopic (LP) vs robotic (RALP) pyeloplasty. Material and Methods: A multicenter prospective review was conducted of pyeloplasty surgeries performed at five high-volume centers between 2014 and 2018. Demographic data, history of prenatal hydronephrosis, access type, MAG3 renogram and differential renal function, surgery time, length of hospital stay, and complication rate (Clavien-Dindo) were recorded. Access type was compared using the Kruskal-Wallis, Chi-square, or Fisher's exact tests. Results: A total of 322 patients were included: 62 OP, 86 LP, and 174 RALP. The mean age was 8.13 (r: 1-16) years, with a statistically significant lower age (mean 5 years) in OP (p < 0.001). There were no significant differences in the distribution of the side affected. Operative time was 110.5 min for OP, 140 min for LP, and 179 min for RALP (p < 0.0001). Hospital stay was significantly shorter in the RALP group than in the other groups (p < 0.0001). There were no differences in postoperative complications and reoperations between the three groups. Conclusions: Minimally invasive surgery for the management of UPJO in children is gaining more acceptance, even in patients younger than 1-year-old. Operative time continues to be significantly shorter in OP than in LP and RALP. Hospital stay was shorter in RALP compared to the other techniques. No differences were found in complication rates, type of complications, and reoperation rate.

Nephrostomy tube versus double J ureteral stent in patients with malignant ureteric obstruction. A systematic review and meta-analysis of comparative studies

ABSTRACT Purpose: We aimed to perform a systematic review to assess perioperative outcomes, complications, and survival in studies comparing ureteral stent and percutaneous nephrostomy in malignant ureteral obstruction. Materials and Methods: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. Meta-analyses were performed on procedural data; outcomes; complications (device-related, accidental dislodgement, febrile episodes, unplanned device replacement), dislodgment, and overall survival. Continuous variables were pooled using the inverse variance of the mean difference (MD) with a fixed effect, and 95% confidence interval (CI). The incidences of complications were pooled using the Cochran-Mantel-Haenszel method with the random effect model and reported as Odds Ratio (OR), and 95% CI. Statistical significance was set two-tail p-value <0.05 Results: Ten studies were included. Procedure time (MD −10.26 minutes 95%CI −12.40-8.02, p<0.00001), hospital stay (MD −1.30 days 95%CI −1.69 − −0.92, p<0.0001), number of accidental tube dislodgments (OR 0.25 95% CI 0.13 - 0.48, p<0.0001) were significantly lower in the stent group. No difference was found in mean fluoroscopy time, decrease in creatinine level post procedure, overall number of complications, interval time between the change of tubes, number of febrile episodes after diversion, unplanned device substitution, and overall survival. Conclusion: Our meta-analysis favors stents as the preferred choice as these are easier to maintain and ureteral stent placement should be recommended whenever feasible. If the malignant obstruction precludes a stent placement, then PCN is a safe alternative.

Immunoglobulin G4-related retroperitoneal fibrosis / Fibrosis retroperitoneal relacionada con IgG4

Abstract Some patients diagnosed with idiopathic retroperitoneal fibrosis could be reclassified as IgG4-related disease (IgG4-RD). Classification criteria have not been uniform and prevalence of IgG4-related retroperitoneal fibrosis (IgG4-RPF) is unknown in our region. We aimed to describe IgG4-RPF frequency relying on criteria published recently and comparing clinical, histopathologic and radiologic features with non-IgG4-RPF. From January, 2005 to December, 2020, nineteen adults with histopathologic diagnosis of idiopathic retroperitoneal fibrosis were included in a dynamic retrospective cohort at Hospital Italiano de Buenos Aires. Pathology slides were reviewed and immunohistochemistry was performed and assessed for each case. We used classification criteria described in 2019 American College of Rheumatology/European League Against Rheumatism to identify IgG4-RD cases. Ten of 19 patients met criteria for IgG4-RPF. Median age was similar in two subsets (61 versus 55, p = 0.2) and both had male predominance. Three out of 10 patients (p = 0.2) featured other manifestations of IgG4-RD in the IgG4-RPF group, and periaortic fibrosis was the most significant finding in images (p = 0.01). Corticosteroids were mostly used as therapy, followed by azathioprine and rituximab. Most patients did not receive specific treatment. IgG4-RPF patients had dense lymphocytic infiltrate and 8 out of 10 showed storiform fibrosis (p = 0.02). IgG4+ cells/hpf and IgG4/IgG ratio were significantly higher (p = 0.01). Over half of the patients in our cohort met the criteria of IgG4-RPF. New criteria may harmonize the identification of IgG4-RD. As IgG4-RD may be reversible at initial stages, these findings may lead to early recognition, treatment and integral follow-up.

Resumen Muchos pacientes con diagnóstico de fibrosis retroperitoneal idiopática (FRI) pueden ser reclasificados como enfermedad relacionada con IgG4 (ER- IgG4). Los criterios diagnósticos no han sido uniformes y la frecuencia de fibrosis retroperitoneal relacionada con IgG4 en nuestra región es desconocida. El objetivo fue describir la frecuencia de ER-IgG4 en pacientes clasificados como FRI y comparar características clínicas, histopatológicas y de laboratorio con aquellos que no reunían criterios de la enfermedad. Se incluyeron 19 adultos en un estudio de cohorte retrospectiva dinámica con diagnóstico anatomopatológico de FRI, en el Hospital Italiano de Buenos Aires, desde enero de 2005 hasta diciembre de 2020. Se revisaron las biopsias y se realizó inmun ohistoquímica en cada una. Se consideró caso al paciente que reunía los criterios de la American College of Rheumatology/European League Against Rheumatism 2019. Diez pacientes reunieron criterios de ER-IgG4. La mediana de edad fue similar en ambos grupos (61 vs. 55, p = 0.2) y en ambos hubo predominio masculino. Tres de 10 pacientes (p = 0.2) tuvieron otras manifestaciones de ER-IgG4 y la fibrosis periaórtica fue el hallazgo más significativo en los estudios por imágenes (p = 0.01). Los corticoides fueron las drogas más utilizadas seguidos por azatioprina y rituximab, pero la mayoría no reci bió tratamiento específico. Todos los pacientes con fibrosis retroperitoneal relacionada con IgG4 presentaron infiltrado linfocitario denso y 8/10 fibrosis estoriforme (p = 0.01), así como las células IgG4+/hpf y ratio IgG4/ IgG fueron significativamente mayores (p = 0.01). Más de la mitad de los pacientes con FRI cumplieron criterios de ER-IgG4. Los nuevos criterios diagnósticos podrían contribuir a homogeneizar la identificación de ER-IgG4. Dado que esta enfermedad puede ser reversible en estadios tempranos, estos resultados promueven aumentar el conocimiento de la entidad para tratamiento precoz y seguimiento integral.

Study about renal injury of unilateral ureteral obstruction model with time / 中国医师杂志

Objective:The unilateral (left) ureteral obstruction (UUO) model was established in mice to explore the changes of renal injury with time and the related mechanisms.Methods:Fifty mice were randomly divided into two groups: sham group and UUO group (UUO model was made by unilateral ureteral ligation). The biochemical indexes, left kidney weight/final weight (LR/BW) and right kidney weight/final weight (RR/BW) of the two groups at different time points were observed, and the left kidney weight/right kidney weight ratio (LR/RR) was calculated. Hematoxylin-eosin (HE), Masson and periodic acid-Schiff (PAS) staining were used to detect the pathological changes of the kidney in mice. Immunofluorescence staining was used to observe the loss of peritubular capillaries (PTC), proliferation of renal parenchymal cells (Ki67 + cells), macrophages (CD68 + markers), infiltration of fibroblasts and expression of Wnt/β-catenin in the kidney of mice. Results:The weight of mice in UUO group decreased rapidly [(18.2±1.1)g vs (22.4±1.2)g] on the third day of modeling, then slowly increased until the 28th day, and significantly decreased [(17.5±0.8)g] on the 60th day; LR/RR and LR/BW increased significantly in the third day, and then decreased gradually; Renal function of mice in UUO group deteriorated significantly on the 60th day [serum creatinine (0.89±0.09)mg/dl, urea nitrogen (41.26±5.65)mg/dl]. In UUO group, renal tubulointerstitial fibrosis and glomerulosclerosis were observed under light microscope in the obstructed kidney; with the passage of time, PTC loss gradually increased; macrophages increased significantly in the left renal parenchyma at first, but began to decrease 28 days later; the number of fibroblasts increased significantly in the first 14 days of the obstructed side (left side) kidney, and then decreased to the normal level; There was no significant difference in the cell number of the non obstructive kidney between UUO group and sham group; The immunofluorescence intensity expression of Wnt/β- catenin of obstructive side (left side) in UUO group was significantly up-regulated in the first 14 days after renal injury, and decreased after 28 days.Conclusions:The development of UUO renal fibrosis involves many changes, including PTC loss, macrophage infiltration, fibroblast activation and expression, but these changes weaken with time.

Effect of Yishen Huoxue Prescription on Endothelial Structure and Function in Mice with Renal Interstitial Fibrosis / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Yishen Huoxue prescription in renal interstitial fibrosis （RIF） from the perspective of endothelial cell and cell energy metabolism. MethodThe model was successfully established by unilateral ureteral obstruction （UUO）. Seventy-five SPF C57BL/6 mice were randomly divided into a model group， a resveratrol group （50 mg·kg-1·d-1）， three Yishen Huoxue prescription low， medium， and high-dose groups （7.1， 14.2， 28.4 g·kg-1·d-1）， with 15 mice in each group. In addition， another 15 mice were used to prepare sham operation model. Mice in the sham operation group and the model group were gavaged with equal volume of normal saline. All mice were sacrificed on 7， 14， and 21 d after modeling. The protein expression of platelet endothelial cell adhesion molecule 31 （CD31） was detected by immunohistochemical S-P method. The expression of α-smooth muscle actin （α-SMA）， collagen Ⅳ （Col-Ⅳ）， angiopoietin 1（Ang-1） and tyrosine kinase receptors 2 （Tie-2）， vascular endothelial growth factor （VEGF）， vascular endothelial cadherin （VE-cadherin）， and occludin in renal tissues was detected by Western blotting. The mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin in renal tissues were detected by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the levels of reactive oxygen species （ROS） in mice were detected by enzyme linked immunosorbent assay （ELISA）. ResultAs compared with the sham operation group， the expression of CD31 in renal tissues of the model group was significantly decreased and worsened with the extension of modeling time （P<0.05）， α-SAM and Col-Ⅳ protein expression levels were significantly increased （P<0.01）， but the expression of CD31 was stable in 14-21 d. ROS levels were significantly increased （P<0.01）， and the protein and mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin were significantly down-regulated （P<0.01）. As compared with the model group， the expression of CD31 was increased （P<0.05）， and α-SAM and Col-Ⅳ in the resveratrol group and the medium and high-dose Yishen Huoxue prescription groups were significantly decreased （P<0.01）. The ROS content was significantly decreased （P<0.01）， and the protein and mRNA expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin were up-regulated （P<0.01）， As compared with the resveratrol group， the protein expressions of Ang-1/Tie-2， VEGF， VE-cadherin， and occludin in the medium and low-dose Yishen Huoxue prescription groups were significantly different （P<0.01）. There was no significant difference in the mRNA expressions of CD31 and Ang-1/Tie-2 in the high-dose Yishen Huoxue prescription group， and no significant difference in the ROS level in the medium-dose Yishen Huoxue prescription group. ConclusionThe anti-RIF effect of Yishen Huoxue prescription may be related to promoting vascular endothelial repair， regulating mitochondrial ROS to reduce oxidative stress， protecting the integrity of renal endothelial structure， delaying cell apoptosis， and maintaining cell energy metabolism.

Efficacy and safety of laparoscopic nipple-inserted ureteral bladder reimplantation for the treatment of ureteral stricture in kidney recipients / 中华泌尿外科杂志

Objective:To evaluate the safety and efficacy of laparoscopic nipple-inserted ureteral bladder reimplantation in the treatment of ureteral stricture in kidney recipients.Methods:Two patients with ureteral stenosis after kidney transplantation who underwent laparoscopic nipple-inserted ureteral bladder reimplantation in our hospital in November 2020 and May 2021 were retrospectively analyzed. Case 1, Female, 54 years old, the patient found mild hydronephrosis in the transplanted kidney 2 years before the operation. Ultrasound showed aggravated hydronephrosis 1 week before the operation, and the width of the renal pelvis was 2.9 cm. Nephrostomy was performed before the operation, and antegrade radiography showed that the ureteral anastomosis was narrow, about 2 cm in length, and the grade of ureteral stenosis in the transplanted kidney was grade 3. Case 2, Male, 56 years old, the patient was previously diagnosed with transplanted kidney hydronephrosis, ureterolithiasis and ureteral stricture, and had undergone percutaneous nephrolithotripsy for transplanted kidney and balloon dilatation for ureteral stricture. However, the hydronephrosis and calculus of the transplanted kidney recurred. One month before the operation, due to sudden anuria, a nephrostomy was performed in our hospital. Ultrasound indicated that the transplanted renal pelvis was dilated, and the width of the renal pelvis was 3.1 cm. The grade of ureteral stricture of the transplanted kidney was grade 3. Both patients underwent transabdominal laparoscopy to dissociate and disconnect the ureter, and performed ureteral papillaplasty outside the abdominal cavity to complete ureteral reimplantation. Data on operation time, intraoperative blood loss, intraoperative and postoperative complications, and postoperative follow-up data were collected.Results:Both operations were successfully completed. The operation time was 145 and 180 minutes respectively. The intraoperative blood loss was 30 ml and 50 ml, respectively. The patient had no postoperative complications, and the renal function recovered compared with before. The double J tube was removed 12 weeks after the operation, and ultrasound showed that the width of the renal pelvis recovered to 0.8 cm and 1.1 cm respectively. The two patients were followed up for 18 and 12 months, respectively, and no recurrence of hydronephrosis was found.Conclusions:Laparoscopic nipple-inserted ureteral bladder reimplantation is a safe and effective method for the treatment of allograft ureteral stenosis, which has the advantages of minimally invasive, faster recovery, and fewer complications.

Amelioration of nebivolol on renal interstitial fibrosis in UUO rats based on proteomic analysis / 中国临床药理学与治疗学

AIM: To explore the effect and mechanism of nebivolol on renal interstitial fibrosis(RIF) in unilateral ureteral obstruction (UUO) model through TMT proteomics. METHODS: SD rats were divided into Sham group, UUO group, Neb group(UUO rats treated with nebivolol 10 mg·kg-1·d-1, i.g.). Left kidney was collected from rat on 7th, 14th and 21th day after modeling. HE staining was used to observe renal structure and Masson's staining was used to examine RIF. Proteomic and bioinformatics were conducted to screen and analysis the differential expressed proteins contrary regulated between UUO/Sham and Neb/UUO 21d after obstruction. Western blot were used to confirm protein expressions. RESULTS: Compared with Sham group, RIF in UUO rats aggravated gradually. Administration of nebivolol for 21 d ameliorated RIF in UUO rats. A total of 179 differential expressed proteins contrary regulated were identified shared between UUO/Sham and Neb/UUO groups. KEGG enrichment analysis and PPI showed that these differential expressed proteins were mainly involved in spliceosome pathway. Results of Western blot for Rbm8a, Srsf9 and Sart1 were in line with the results of proteomics. CONCLUSION: Spliceosome may play key role in the amelioration of nebivolol on RIF in UUO rats.

Antegrade double-J stenting as an alternative to the retrograde approach: experience of the first 150 cases at a single center in Brazil / Implante anterógrado de cateter duplo J como alternativa para abordagem retrógrada: experiência dos primeiros 150 casos em centro único no Brasil

Abstract Objective: To present our clinical experience with percutaneous antegrade ureteral stenting. Materials and Methods This was a single-center retrospective study in which we reviewed the electronic medical records of patients who underwent percutaneous image-guided antegrade ureteral stenting between January 2016 and August 2020. We evaluated 90 patients (48 men). The mean age was 61.4 ± 15 years (range, 30-94 years). Patients were divided into two main groups: those with malignant neoplasms; and those with non-neoplastic disease. Technical and clinical success of the procedure were defined, respectively, as maintenance of the patency of the urinary tract, with a reduction in the degree of hydronephrosis, and as a reduction in the level of nitrogenous waste. Postprocedural complications were categorized as major or minor according to the CIRSE classification. Results: The study sample comprised 150 antegrade stenting procedures performed in 90 patients, most of whom had previously undergone retrograde stenting that was unsuccessful. The stenting was bilateral in 60 patients and unilateral in 30. Technical success was achieved in 143 (95.3%) of the procedures, whereas seven procedures (4.6%) were unsuccessful. Failed procedures were characterized by inability to place a stent or migration of a stent after its placement. Complications occurred in 12 (8.0%) of the procedures. Of those 12 complications, two were classified as major (bleeding) and 10 were classified as minor (lumbar pain or infection). The most common techniques used were the over-the-wire technique and the modified technique (in 58.0% and 42.0% of the cases, respectively). In seven cases (4.7%), a nephrostomy tube was inserted. Conclusion: Percutaneous antegrade ureteral stenting is a safe, effective method for the management of ureteral injuries and obstructions, due to malignant or benign causes, when the retrograde approach has failed.

Resumo Objetivo: Apresentar os resultados clínicos de 150 casos de inserção anterógrada de cateter duplo J. Materiais e Métodos: Foram revisados os prontuários eletrônicos de pacientes submetidos a inserção percutânea de cateter duplo J guiada por imagem entre janeiro de 2016 e agosto de 2020. Um total de 90 pacientes (48 homens e 42 mulheres; faixa etária, 30-94 anos; idade média, 61,4 ± 15 anos) foi incluído no estudo. Os pacientes foram classificados em dois grupos principais: neoplasia maligna e doença não neoplásica. O sucesso técnico e clínico do procedimento foi definido como a manutenção da perviedade da via urinária com redução do grau de hidronefrose e redução dos níveis das escórias nitrogenadas. As complicações pós-procedimento foram classificadas em maiores e menores, de acordo com o sistema de classificação CIRSE. Resultados: Foram realizados 150 procedimentos (90 pacientes) no período, sendo bilateral em 60 pacientes e unilateral em 30. Houve sucesso técnico em 143 casos (95,3%) e falhas em sete (4,7%), caracterizadas por migração e não progressão do cateter. Nossas taxas de complicações foram de 8,0% (12 casos), sendo dois maiores (sangramento) e 10 menores (principalmente dor lombar). As técnicas mais utilizadas para a inserção foram over the wire (58,0%) e modificada (42,0%). Em sete pacientes (4,7%) foi realizada nefrostomia percutânea. Conclusão: A inserção anterógrada do cateter duplo J é um método seguro e eficaz para o tratamento de obstruções uretéricas devidas a causas e lesões malignas e benignas, quando há uma falha na abordagem cistoscópica (retrógrada).

Exclusión renal por endometriosis profunda ureteral: a propósito de un caso / Renal exclusion due to deep infiltrating ureteral endometriosis: a case report

INTRODUCCIÓN: La endometriosis ureteral es una afección rara que afecta al 0.01-1,7% de las mujeres con endometriosis. Hasta un 30% cursa de forma asintomática y un 11,5-14,7% pueden evolucionar con falla renal. La falta de diagnóstico de la enfermedad puede terminar en una uropatía obstructiva y falla renal irreversible. Se presenta el caso de una paciente con afectación grave de la función renal secundaria a endometriosis profunda con compromiso ureteral. CASO CLÍNICO: Mujer de 35 años con endometriosis que consultó por exacerbación de los síntomas. En su estudio destaca, en la resonancia magnética, el hallazgo de endometriosis pélvica profunda y compromiso endometriósico intrínseco del uréter distal derecho, provocando una acentuada hidroureteronefrosis. El cintigrama renal demuestra acentuado compromiso de la función renal derecha, con una función relativa del 7%. Se realizaron nefrectomía total derecha y resección de enfermedad pélvica profunda laparoscópica, sin incidentes. CONCLUSIONES: La endometriosis ureteral representa un desafío diagnóstico y terapéutico. El manejo multidisciplinario entre radiólogos, ginecólogos y urólogos, mediante el diseño de una estrategia quirúrgica individualizada, es imprescindible para definir el tratamiento óptimo de estas pacientes.

INTRODUCTION: Ureteral endometriosis is a rare entity that affects 0.01-1,7% of women with endometriosis. Up to 30% of the patients are asymptomatic and 11.5-14.7% will develop renal failure. Misdiagnosis can lead to obstructive uropathy and permanent renal failure. We present the case of a patient with severe compromise of renal function secondary to deep infiltrating endometriosis with ureteral involvement. CASE REPORT: A 35-year-old woman with endometriosis presented with exacerbation of symptoms. Magnetic resonance showed deep pelvic endometriosis and intrinsic endometriotic involvement of the right distal ureter, causing a marked hydroureteronephrosis. Renal scintigram showed a severe compromise of the right renal function, with a relative function of 7%. Through laparoscopy a total right nephrectomy and resection of deep infiltrating endometriosis was performed. The patient had a satisfactory recovery in the postoperative period. CONCLUSIONS: Ureteral endometriosis presents a diagnostic and therapeutical challenge. Joint multidisciplinary management between radiologists, gynecologists and urologists through the design of an individualized surgical strategy is essential to define the optimal treatment for these patients.

Comparison of retrograde ureterorenoscopy (URS) and percutaneous anterograde ureteroscopy for removal of impacted upper ureteral stones >10mm in the elderly population

ABSTRACT Purpose: We aimed to compare the success and complication rates of the anterograde and retrograde Ureterorenoscopy (URS) for impacted upper ureteral stones in patients > 65 years of age. Materials and Methods: Data of 146 patients >65 years of age and underwent anterograde URS (n=68) in supine position or retrograde URS (n=78) for upper ureteral impacted stones>10 mm between January 2014 and September 2018 were collected prospectively. The groups were compared for success and complication rates, duration of operation, hospital stay, and ancillary procedures. Results: Anterograde and retrograde URS groups were similar for demographic and stone related characteristics. The success rate of the anterograde URS group was significantly higher than the retrograde URS group (97.1% vs. 78.2%, p=0.0007). The complication rates were similar for the two groups (p=0.86). Clavien grade I and II complications were observed in 3 patients in each group. The mean hemoglobin drop was 0.5 g/dL in the anterograde URS group and blood transfusion was not performed in any of the patients. The mean duration of operation was 41.2±12.5 minutes in the mini-PNL group and 59.6±15.1 minutes in the RIRS group and the difference was statistically significant (p=0.02). The median duration of hospitalization was 1 day for both groups. Conclusions: Performing anterograde URS in supine position provided better success rates and similar complication rates compared to retrograde URS. Based on these results anterograde URS shall be considered as one of the primary treatment options for management of impacted upper ureteral stones in the elderly population.

Efficacy analysis of single-port intravesical laparoscopic Politano-Leadbetter for primary obstructive megaureter in adolescents / 中华泌尿外科杂志

Objective:To investigate the efficacy of single-port intravesical laparoscopic Politano-Leadbetter in the treatment of adolescent primary obstructive megaureter.Methods:Retrospective analysis was performed on the clinical data of 11 adolescents with primary obstructive megaureter who received single-port intravesical laparoscopic Politano-Leadbetter in Fujian Provincial Hospital from January 2018 to November 2019, including 7 males and 4 females, 8 patients with left stenosis and 3 patients with right stenosis. The mean age was (13.5±2.4) years old, and the mean weight was (49.4±11.2) kg. Before surgery, the anteroposterior diameter of the affected renal pelvis was (3.25±0.69) cm, the maximum diameter of the ureter was (2.25±0.48) cm, the thickness of the affected renal cortex was (1.34±0.52) cm, and the renal function was (36.00±2.86) %. All patients underwent Politano-Leadbetter by single-port intravesical laparoscopic. Suprapubic bladder approach was used to establish a single-hole air bladder channel, and the end of the ureter was dislocated and cut, the submucosal tunnel of the bladder was established, and the end of the ureter was re-embedded. The Politano-Leadbetter ureteral replantation was completed.The dilatation and tortuousness of the affected renal pelvis and ureter and the changes of renal function of the affected kidney were analyzed before and after operation.Results:All operations were completed successfully.The operative time was (95.6±18.5) min, the intraoperative blood loss was (6.8±2.3) ml, the postoperative indwelling catheter time was (4.5±1.8) d, and the average hospital stay was (6.2±2.4) d. Postoperative follow-up time was (13.6±4.3) months.12 months after surgery, the anteroposterior diameter of the affected renal pelvis and the maximum diameter of the ureter were (2.00±0.45) cm and (1.18±0.22) cm, which were significantly lower than those before surgery ( P< 0.05). The thickness of the renal cortex was (2.17±0.49) cm, and the renal function was (44.00±1.41) %, which was significantly increased compared with that before operation ( P<0.05). Diuretic nephrogram showed no mechanical obstruction or no obstruction curve. One patient developed urinary tract infection 6 weeks after operation and recovered after removal of double J tubes.The other patient presented degree I ureteral reflux 6 months and 1 year after surgery, without urinary tract infection and low back pain.All the other children recovered well without postoperative complications.All parents were satisfied with the incision. Conclusions:Single-port intravesical laparoscopic Politano-Leadbetter for the treatment of adolescents with primary obstructed megareter can improve hydronephelectasis of the renal pelvis and renal function of the affected kidney, and overcome the difficulty of injury due to fat pad hypertrophy in the bladder area above the pubic bone and the establishment of conventional pneumo-bladder laparoscopy, the operation effect is ideal, few complications, safe and feasible.

The study on bone marrow-derived mesenchymal stem cells in alleviating tubulointerstitial injury in unilateral ureteral obstruction model / 中国医师进修杂志

Objective:To investigate the effect and mechanism of bone marrow-derived mesenchymal stem cells (MSCs) in alleviating renal injury in unilateral ureteral obstruction (UUO) model.Methods:MSCs were cultured, and then transplanted into a UUO model through the tail vein. Histology, cell apoptosis, peritubular capillary (PTC) loss and β-catenin expression were examined on the fourteen day after surgery.Results:Renal interstitial fibrosis in the MSCs group was significantly attenuated compared with that in the UUO group (HE: 1.60 ± 0.35 vs. 3.34 ± 0.23; MASSON: 21.32 ± 7.54 vs. 51.08 ± 4.45). Moreover, MSCs treatment inhibited the loss of peritubular capillaries (PTC) (13.56 ± 4.65 vs. 60.16 ± 10.24), cell apoptosis (14.32 ± 3.54 vs. 28.16 ± 6.21) and β-catenin expression (29.33 ± 6.45 vs. 39.51 ± 8.42).Conclusions:MSCs infusion is a promising therapeutic strategy for promoting kidney repair in chronic renal fibrosis model. The mechanism maybe that it inhibits the loss of peritubular capillaries (PTC) , cell apoptosis and β-catenin expression.

MicroRNA-302b mitigates renal fibrosis via inhibiting TGF-ß/Smad pathway activation

Renal fibrosis is one of the most significant pathological changes after ureteral obstruction. Transforming growth factor-β (TGF-β) signaling pathway plays essential roles in kidney fibrosis regulation. The aims of the present study were to investigate effects of microRNA-302b (miR-302b) on renal fibrosis, and interaction between miR-302b and TGF-β signaling pathway in murine unilateral ureteral obstruction (UUO) model. Microarray dataset GSE42716 was downloaded by retrieving Gene Expression Omnibus database. In accordance with bioinformatics analysis results, miR-302b was significantly down-regulated in UUO mouse kidney tissue and TGF-β1-treated HK-2 cells. Masson's trichrome staining showed that miR-302b mimics decreased renal fibrosis induced by UUO. The increased mRNA expression of collagen I and α-smooth muscle actin (α-SMA) and decreased expression of E-cadherin were reversed by miR-302b mimics. In addition, miR-302b up-regulation also inhibited TGF-β1-induced epithelial mesenchymal transition (EMT) of HK-2 cells by restoring E-cadherin expression and decreasing α-SMA expression. miR-302b mimics suppressed both luciferase activity and protein expression of TGF-βR2. However, miR-302b inhibitor increased TGF-βR2 luciferase activity and protein expression. Meanwhile, miR-302b mimics inhibited TGF-βR2 mRNA expression and decreased Smad2 and Smad3 phosphorylation in vivo and in vitro. Furthermore, over-expression of TGF-βR2 restored the miR-302b-induced decrease of collagen I and α-SMA expression. In conclusion, this study demonstrated that miR-302b attenuated renal fibrosis by targeting TGF-βR2 to suppress TGF-β/Smad signaling activation. Our findings showed that elevating renal miR-302b levels may be a novel therapeutic strategy for preventing renal fibrosis.

Bilateral ureterolithiasis in a 7-month-old cat / Ureterolitíase bilateral em um gato de sete meses de idade

ABSTRACT: Feline ureteral obstruction can have several causes; however, ureterolithiasis has been increasing in occurrence. The restriction of urinary flow induced by the obstruction has harmful consequences to the body and can lead to acute renal failure. Calcium oxalate ureterolithiasis is reported in older cats, aged mean 12 years old. A case of bilateral ureteral obstruction in a 7-month-old mixed breed cat is described in this report. Imaging tests such as abdominal ultrasonography, radiography and excretory urography were performed to determine the diagnosis. The surgical procedure of bilateral ureterotomy was then performed, which allowed the improvement of the urinary flow of both kidneys and the resolution of clinical signs caused by uremia. The quantitative analysis of both uroliths revealed the composition of 100% monohydrate calcium oxalate. Calcium oxalate stones can also cause ureteral obstruction in young cats; although, are less common in this age. When conservative treatment fails, surgical intervention becomes necessary for the rapid return of renal function. To author's knowledge this is the first report of a ureterolithiasis caused by calcium oxalate in a young cat.

RESUMO: A obstrução ureteral em gatos pode ter diversas causas, entretanto, a ureterolitíase vem apresentando um aumento na sua ocorrência. A restrição do fluxo urinário induzida pela obstrução traz consequências graves ao organismo, podendo levar a insuficiência renal aguda. A ureterolitíase por cálculos de oxalato de cálcio é relatada em gatos mais velhos, com média de idade de 12 anos. Um caso de obstrução ureteral bilateral em um gato, SRD, com sete meses de idade é descrito nesse relato. Exames de imagem, como ultrassonografia e radiografia abdominais e urografia excretora, foram realizados para confirmar o diagnóstico. O procedimento cirúrgico de ureterotomia bilateral foi então realizado, permitindo a melhora do fluxo urinário de ambos os rins e dos sinais clínicos de uremia. A análise quantitativa de ambos os urólitos revelou a composição de 100% oxalato de cálcio monohidratado. Cálculos de oxalato de cálcio são um diagnóstico diferencial para obstrução ureteral também em gatos jovens, apesar de serem menos comuns. Quando há falha no tratamento conservador, a intervenção cirúrgica torna-se necessária para o rápido restabelecimento e preservação da função renal. No conhecimento dos autores, esse é o primeiro relato de ureterolitíase causada por oxalato de cálcio em um gato jovem.

Antegrade insertion of a double J catheter in the treatment of malignant ureteral obstruction: a retrospective analysis of the results obtained with a modified technique at a university hospital / Inserção anterógrada de cateter duplo J no tratamento de obstruções ureterais malignas: análise retrospectiva dos resultados de uma técnica modificada em um hospital universitário

Abstract Objective: To analyze the results obtained with a modified antegrade double J catheter insertion (JJ stenting) technique in patients with urinary tract obstruction due to malignancy. Materials and Methods: This was a retrospective analysis of data collected from patients undergoing antegrade JJ stenting for malignant ureteral obstruction in the interventional radiology department of our institution between March 1, 2017 and May 31, 2019. Results: Antegrade JJ stenting was performed in 32 patients (20 women and 12 men). The mean age was 66.2 years among the females and 61.5 years among the males. A total of 53 antegrade JJ stenting procedures were performed. The procedure was successful in 50 cases and failed in 3 (due to migration of the double J catheter in 2 and due to technical failure in 1). Complications occurred in 3 patients (low back pain, in 1, subcapsular hematoma, in 1, and pyelonephritis, in 1). The procedure time ranged from 14 min to 55 min. Conclusion: In patients with ureteral obstruction due to malignancy, antegrade JJ stenting is safe and effective. The technique selected in our study is easily reproduced and can be performed by a trained professional.

Artigos Objetivo: Análise retrospectiva dos resultados de uma técnica modificada de inserção anterógrada de cateter duplo J em pacientes com obstrução do trato urinário por causas oncológicas. Materiais e Métodos: Coleta e análise retrospectiva de dados de pacientes submetidos a inserção anterógrada de cateter duplo J por obstruções ureterais neoplásicas no departamento de radiologia intervencionista da instituição, entre 1º de março de 2017 e 31 de maio de 2019. Resultados: No total, 32 pacientes foram submetidos a inserção anterógrada de cateter duplo J, sendo 20 mulheres e 12 homens. A média de idade foi de 66,2 anos para o sexo feminino e 61,5 anos para o sexo masculino. Cinquenta e três inserções anterógradas de cateter duplo J foram realizadas. O número de procedimentos bem sucedidos foi 50 e houve 3 falhas (2 migrações do cateter duplo J e 1 insucesso técnico). As complicações ocorreram em 3 pacientes (1 dor lombar, 1 hematoma subcapsular e 1 pielonefrite). O tempo de procedimento variou entre 14 e 55 minutos. Conclusão: A inserção anterógrada de cateter duplo J em pacientes com obstrução ureteral por causas malignas é eficaz e segura. A técnica descrita no nosso estudo é de fácil reprodução, podendo ser executada por um profissional capacitado.