Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus (DM). Qianjin Wenwu decoction (QWD), a well-known traditional Korean medicine, has been used for the treatment of DKD, with satisfactory therapeutic effects. This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD. The results demonstrated that a total of 13 active components in five types were found in QWD, including flavonoids, flavonoid glycosides, phenylpropionic acids, saponins, coumarins, and lignins. Two key proteins, TGF-β1 and TIMP-1, were identified as the target proteins through molecular docking. Furthermore, QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction (UUO). Hematoxylin & eosin (H&E) and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice. We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF- β1 in DKD treatment. These findings explain the underlying mechanism of QWD for the treatment of DKD, and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.
Rats ; Mice ; Animals ; Ureteral Obstruction/metabolism* ; Kidney/metabolism* ; Tissue Inhibitor of Metalloproteinase-1/metabolism* ; Molecular Docking Simulation ; Rats, Sprague-Dawley ; Kidney Diseases/drug therapy* ; Extracellular Matrix/metabolism* ; Flavonoids/metabolism* ; Fibrosis

OBJECTIVES: To explore the mechanism of transforming growth factor-β1 (TGF-β1) induce renal fibrosis. METHODS: Renal fibroblast NRK-49F cells treated with and without TGF-β1 were subjected to RNA-seq analysis. DESeq2 was used for analysis. Differentially expressed genes were screened with the criteria of false discovery rate<0.05 and l o g 2 F C >1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for differentially expressed genes. Genes encoding transcription factors were further screened for differential expression genes. Then, the expression of these genes during renal fibrosis was verified using unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis model and a public gene expression dataset (GSE104954). RESULTS: After TGF-β1 treatment for 6, 12 and 24 h, 552, 1209 and 1028 differentially expressed genes were identified, respectively. GO analysis indicated that these genes were significantly enriched in development, cell death, and cell migration. KEGG pathway analysis showed that in the early stage of TGF-β1 induction (TGF-β1 treatment for 6 h), the changes in Hippo, TGF-β and Wnt signaling pathways were observed, while in the late stage of TGF-β1 induction (TGF-β1 treatment for 24 h), the changes of extracellular matrix-receptor interaction, focal adhesion and adherens junction were mainly enriched. Among the 291 up-regulated differentially expressed genes treated with TGF-β1 for 6 h, 13 genes (Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Ahr, Foxo1, Myc, Tcf7, Foxc2, Glis1) encoded transcription factors. Validation in a cell model showed that TGF-β1 induced expression of 9 transcription factors (encoded by Snai1, Irf8, Bhlhe40, Junb, Arid5a, Vdr, Lef1, Myc, Tcf7), while the expression levels of the other 4 genes did not significantly change after TGF-β1 treatment. Validation results in UUO-induced mouse renal fibrosis model showed that Snai1, Irf8, Bhlhe40, Junb, Arid5a, Myc and Tcf7 were up-regulated after UUO, Vdr was down-regulated and there was no significant change in Lef1. Validation based on the GSE104954 dataset showed that IRF8 was significantly overexpressed in the renal tubulointerstitium of patients with diabetic nephropathy or IgA nephropathy, MYC was highly expressed in diabetic nephropathy, and the expressions of the other 7 genes were not significantly different compared with the control group. CONCLUSIONS TGF-β1 induces differentially expressed genes in renal fibroblasts, among which Irf8 and Myc were identified as potential targets of chronic kidney disease and renal fibrosis.
Mice ; Animals ; Humans ; Transforming Growth Factor beta1/metabolism* ; Diabetic Nephropathies/pathology* ; Transcriptome ; Signal Transduction ; Kidney ; Ureteral Obstruction/pathology* ; Fibrosis ; Interferon Regulatory Factors ; Transforming Growth Factor beta/metabolism* ; DNA-Binding Proteins/metabolism* ; Transcription Factors/metabolism*

OBJECTIVE: To comprehensively evaluate the long-term efficacy and safety of coated metal stent implantation for ureteroscopic lithotripsy related refractory ureteral stricture (URL-rUS). METHODS: Electronic medical records of 30 patients (31 affected renal units) receiving coated metal stent implantation for URL-rUS from Sept. 2018 to Aug. 2021 at Peking University People' s Hospital were reviewed for analysis. Coated metal stents were implanted in retrograde approach via ureteroscope. Last outpatient follow-up was set as endpoint. Baseline information, stricture characteristics and decompression strategy before coated metal stent implantation were retrospectively collected. Serum creatinine (Scr) concentration and renal pelvis width (RPW) were used as renal function indicators. Peri-operative and long-term complications and according outcomes were recorded. For the patients who had double J tubes implanted for drainage before operation, Ureteral Stent Symptom Questionnaire (USSQ) was applied to evaluate the stent-related discomforts and quality of life (QoL) before and after surgery. Data analysis was conducted with SPSS (version 25.0; SPSS, Chicago, IL, USA). RESULTS: Totally 30 patients with 31 affected renal units were included. All the patients previously underwent unsuccessful traditional endoscopic balloon dilation or endoureterotomy before receiving coated metal stent implantation. The mean age was (45.5±9.3) years old. The median follow-up time were 14 (6-36) months. All coated metal stents were successfully placed with a median duration of 60 (30-195) min. No severe peri-operative complications occurred. At endpoint, 28 (90.3%) sides of coated metal stents remained unobstructed with a longest indwelling time of 36 months. Causes of failures included stent migration (1 case, 3.2%), encrustation (1 case, 3.2%) and repeated stent related urinary tract infection (1 case, 3.2%). When compared with the baseline, significant reductions were observed in both Scr concentration and RPW at endpoint [(90.7±19.5) mmol/L vs. (83.1±18.5) μmol/L, P < 0.01, for Scr; (2.5±1.3) cm vs. (1.9±0.8) cm, P < 0.01, for RPW], indicating good preservation of renal function and remission of hydronephrosis. For 26 patients with double J stents before operation, significant reduction of USSQ average score (100.4±6.6 vs. 82.1±4.9, P < 0.01) evidenced better life quality preserving ability of coated metal stent versus double J stent. CONCLUSION Coated metal stent implantation is a safe and minimally invasive management of ureteral stricture providing a satisfying long-term patency rate, after which the patients' quality of life and renal function could be both improved. This method could serve as a promising alternative long-term maintenance treatment option for patients with URL-US, especially when traditional endoscopic interventions failed.
Adult ; Constriction, Pathologic ; Humans ; Lithotripsy ; Metals ; Middle Aged ; Quality of Life ; Retrospective Studies ; Stents/adverse effects* ; Treatment Outcome ; Ureteral Obstruction/surgery* ; Ureteroscopy

OBJECTIVE: To study the trend of surgical type, surgical procedure and etiological distribution of upper urinary tract repair in recent 10 years. METHODS: The preoperative and perioperative variables and follow-up data of upper urinary tract reconstruction surgery in RECUTTER (Reconstruction of Urinary Tract: Technology, Epidemiology and Result) database from 2010 to 2021 were searched, collected and analyzed. The surgical type, surgical procedure, duration of hospitalization, time of operation, incidence of short-term complications, and proportion of the patients undergoing reoperations were compared between the two groups of 2010-2017 period and 2018-2021 period. RESULTS: A total of 1 072 patients were included in the RECUTTER database. Congenital factors and iatrogenic injuries were the main causes of upper urinary tract repair. Among them, 129 (12.0%) patients had open operation, 403 (37.6%) patients had laparoscopic surgery, 322 (30.0%) patients had robot-assisted laparoscopic surgery and 218 (20.3%) patients had endourological procedure. In the last decade, the total number of surgeries showed a noticeable increasing annual trend and the proportion of robot-assisted laparoscopic surgery in 2018-2021 was significantly higher than that in 2010-2017 (P < 0.001). The 1 072 patients included 124 (11.6%) cases of ileal ureter replacements, 440 (41.1%) cases of pyeloplasty, 229 (21.4%) cases of balloon dilation, 109 (10.2%) cases of ureteral reimplantation, 49 (4.6%) cases of boari flap-Psoas hitch surgery, 60 (5.6%) cases of uretero-ureteral anastomosis, 61 (5.7%) cases of lingual mucosal onlay graft ureteroplasty or appendiceal onlay flap ureteroplasty. Pyeloplasty and balloon dilatation had been the main types of surgery, while the proportion of lingual mucosal onlay graft ureteroplasty plus appendiceal onlay flap ureteroplasty had increased significantly in recent years (P < 0.05). In addition, the time of operation was significantly increased (P < 0.05) after 2018, which was considered to be related to the sharp increase in the proportion of robot-assisted laparoscopic surgery. We found that minimally invasive surgery (endourological procedure and robot-assisted laparoscopic surgery) as an independent risk factor (P=0.050, OR=0.472) could reduce the incidence of short-term post-operative complications. CONCLUSION We have justified the value of the RECUTTER database, created by the Institute of Urology, Peking University in data support for clinical research work, and provided valuable experience for the construction of other multi-center databases at home and abroad. In recent 10 years, we have observed that, in upper urinary tract reconstruction surgery, the surgery type tends to be minimally invasive and the surgery procedure tends to be complicated, suggesting the superiority of robot-assisted laparoscopic surgery.
Humans ; Laparoscopy/methods* ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome ; Ureter/surgery* ; Ureteral Obstruction/surgery* ; Urologic Surgical Procedures/methods*

OBJECTIVE: To investigate the efficacy and safety of laparoscopic pyeloplasty combined with ultrasonic lithotripsy via nephroscope in the treatment of ureteropelvic junction obstruction (UPJO) with renal calculi. METHODS: From June 2016 to January 2022, eight patients including five males and three females underwent laparoscopic pyeloplasty combined with ultrasonic lithotripsy via 19.5F(1F≈0.33 mm) nephroscope in Peking University People' s Hospital. The age ranged from 23-51 years (mean: 40.5 years) and the body mass index (BMI) ranged from 18.8-32.4 kg/m² (mean 27.0 kg/m²). The lesion located on the left side in all of the eight patients. Two patients had solitary kidney and one patient had horseshoe kidney. Solitary stone was seen in one patient and the other seven patients suffered multiple stones, with two patients had staghorn stones. The largest diameter of stones ranged from 0.6-2.5 cm (mean: 1.5 cm). CT or ultrasound showed that moderate nephrosis was seen in five patients and severe nephrosis was seen in three patients. During surgery, after exposure of renal pelvis and proximal ureter, a small incision of 1.5 cm was performed in the anterior wall of the renal pelvis, and a 19.5F nephroscope was introduced into renal pelvis through laparoscopic trocar and renal pelvis incision. Stones were fragmented and sucked out by 3.3 mm ultrasonic probe placed through nephroscope. After stones were removed, modified laparoscopic pyeloplasty was performed. RESULTS: Surgery was successfully completed in all of the eight patients without conversion to open surgery. The operation time ranged from 160-254 min (mean 213 min) and the time of nephroscopic management time was 25-40 min (mean: 33 min). The hemoglobin was decreased by 3-21 g/L (mean: 10.3 g/L). The stone-free rate was 75% (6/8 cases), stones were incompletely removed in two patients due to abnormal intrarenal structure. The modified Clavien classification system (MCCS) grade ⅢA complication occurred in one patient postoperatively, which was nephrosis due to intrarenal bleeding, and nephrostomy was performed. With the mean follow-up of 30 months (ranged from 2-68 months), there was no evidence of obstruction in all the patients, and one patient underwent percutaneous nephrolithotomy to treat residual calculi. CONCLUSION Laparoscopic pyeloplasty combined with ultrasonic lithotripsy via 19.5F nephroscope is feasible and safe, and could be a complementary method to treat UPJO and renal calculi.
Adult ; Female ; Humans ; Kidney Calculi/surgery* ; Kidney Pelvis ; Laparoscopy/methods* ; Lithotripsy ; Male ; Middle Aged ; Nephrosis/surgery* ; Ureter ; Ureteral Obstruction/surgery* ; Young Adult

Ureteral stenosis is a comparatively rare complication following hematopoietic stem cell transplantation (HSCT). The etiology is still unclear and most believe that this may be due to the reactivation of BK virus in a state of immunodeficiency. In the later stages of ureteral stenosis with scarring, invasive interventions must be taken to relieve the hydronephrosis. Common treatments, such as D-J stent placement and permanent nephrostomy may not only entail the risk of infection, but also seriously affect the quality of life. Few cases of surgical intervention have been reported. In this article, a 25-year-old female was admitted to Peking University First Hospital suffering from recurrent flank pain. Seven years before, she developed hemorrhagic cystitis and bilateral urethritis 40 days after allogeneic HSCT. After continuous bladder irrigation and antiviral therapy, the left-sided hydronephrosis gradually alleviated while the right-sided one did not improve. D-J stents were used for urine drainage for 7 years before percuta-neous nephrostomy. Preoperative antegrade pyelography revealed significant hydronephrosis in the right kidney with long stricture of proximal-middle ureter. After comprehensive decision, she underwent ileal ureter replacement. The operation was successful. The segmental lesion was dissected and the scar tissue was removed. A 25 cm intestinal tube was isolated to connect the pelvis and bladder. An anti-reflux nipple was created at the distal end of ileal ureter to prevent the potential infection. The blood loss was minimal. After surgery, the drainage tube was removed in 2 weeks, the nephrostomy tube and the D-J stent was removed in 3 months. Follow-up mainly included clinical assessment, serologic testing, renal ultrasonography, blood gas analysis and radiological examination. During the follow-up of 6 years, she was symptom-free and no postoperative complications occurred. The serum creatinine level was stable. No hydronephrosis was observed under ultrasonography. Obvious peristaltic waves and ureteral jets of the ileal ureter was confirmed on cine magnetic resonance urography. To sum up, ureteral stenosis after HSCT is relatively rare. Obstruction caused by scarring is usually irreversible and surgical intervention should be designed according to the location and length of the lesion. Ileal ureter replacement can be a safe, feasible and effective method to solve this kind of complex stricture.
Adult ; Cicatrix ; Constriction, Pathologic/etiology* ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Humans ; Hydronephrosis/surgery* ; Quality of Life ; Ureter/surgery* ; Ureteral Obstruction/surgery*

Background: Cervical cancer is the second most common malignancy among Filipino women. The recent 2018 FIGO guidelines recommend imaging in cases of grossly invasive disease to determine the presence of hydronephrosis, which would immediately classify the disease as at least stage IIIB. CT and MRI are state-of-the-art modalities that can provide such information; however, these are costly and may not be accessible in areas with limited resources. Sonography is a safe and inexpensive alternative in this regard.

Objective: This study aimed to evaluate the diagnostic performance of renal sonography in identifying the presence of ureteral obstruction or hydronephrosis among patients with grossly invasive cervical cancer, with non-enhanced CT as the reference standard.

Methods: A blinded, prospective study was conducted among patients diagnosed with grossly invasive cervical cancer from the Philippine General Hospital. Participants underwent same-day evaluation with both renal sonography and non-enhanced CT. The presence of either ureteral obstruction or hydronephrosis secondary to cervical cancer was independently determined. The sensitivity, specificity, positive predictive value, and negative predictive value of renal sonography were calculated, with non-enhanced CT as the reference standard.

Results: A total of 127 participants were enrolled. The mean age was 46 years, with a range of 24 to 65 years. The majority had stage IIB (41.7%) and stage IIIB (52.0%) disease. On non-enhanced CT, 46 (36.2%) showed evidence of ureteral obstruction or hydronephrosis, while 81 (63.8%) had negative results. On renal sonography, 46 (36.2%) had positive results, and 81 (63.8%) had negative findings. The sensitivity, specificity, and positive and negative predictive values of sonography were 91.3%, 95.1%, 91.3%, and 95.1%, respectively. Among patients with stage IIIB disease, sonography was shown to have higher sensitivity and specificity of 92.1% and 96.4%, respectively. Meanwhile, among patients with stage IB to IIB disease, its sensitivity and specificity were 87.5% and 94.3%, respectively.

Conclusion: Renal sonography has high sensitivity and specificity in the diagnosis of ureteral obstruction or hydronephrosis in patients with grossly invasive cervical cancer. Its sensitivity is higher when used in patients with stage IIIB disease, compared with those having lower-stage tumors.

OBJECTIVE: To summarize the initial clinical experience and follow-up results of the treatment for ureteroileal anastomotic stricture after radical cystectomy with Allium coated metal ureteral stent. METHODS: From September 2018 to September 2019, 8 patients with ureteroileal anastomotic stricture after radical cystectomy underwent Allium ureteral stent insertion in Peking University People's Hospital and People's Hospital of Daxing District. The preoperative renal pelvis width under ultrasound was collected to evaluate the postoperative hydronephrosis, creatinine and urea nitrogen (BUN) before and after surgery, perioperative infection, and stent-related complications. The serum creatinine and BUN, renal pelvis width under ultrasound, urography and abdominal plain film (KUB) were reviewed at the end of 1, 3, and 6 months and annually postoperatively to observe the stent position and morphology. The long-term stent patency rate, complication rate, renal function and hydronephrosis were followed up and analyzed. The t-test or rank-sum test was used to compare the measurement data of the matched sample from the preoperative to the last follow-up. RESULTS: In the study, 6 cases (7 sides) were ureteral ileal conduit stricture, and 2 cases (3 sides) ureteral orthotopic neobladder stricture. Before surgery, 5 patients underwent long-term indwelling of a single J ureteral stent, with an average indwelling time of (20.6±8.8) months and an average replacement frequency of (3.6±1.3) months/time. The mean width of renal pelvis was (26.5±9.1) mm on preoperative renal ultrasonography. Among them, 6 patients were successfully indwelled with Allium coated metal ureteral stent by retrograde approach, and 2 patients by combination of double-endoscopy and ante-retrograde approach. No surgery-related complications during perioperative period were observed. The mean follow-up period was 9.8 months and Allium stent and ureter remained unobstructed in all the patients at the last follow-up without replacement or removal. Compared with preoperative data, the mean width of renal pelvis and mean blood urea nitrogen (BUN) in the last follow-up period were significantly reduced [(26.5±9.1) mm vs. (13.4±2.5) mm, P=0.008; (11.6±2.3) mmol/L vs. (10.2±2.2) mmol/L, P=0.017], however, there were no significant differences in the average serum creatinine or hemoglobin (P>0.05). Ureteroileal anastomotic re-stricture and other stent-related complications were not observed in all the patients by antegrade urography. CONCLUSION Allium coated metal ureteral stent could be used for the treatment for ureteroileal anastomotic stricture, which could maintain relatively long-term patency rate and protect renal function. The indwelling time was longer and it could improve quality of life of patients.
Allium ; Anastomosis, Surgical ; Constriction, Pathologic ; Cystectomy ; Follow-Up Studies ; Humans ; Metals ; Quality of Life ; Stents ; Treatment Outcome ; Ureter ; Ureteral Obstruction/surgery* ; Urinary Diversion

OBJECTIVE: To evaluate the clinical application of indocyanine green (ICG) visualization by near infrared fluorescence laparoscopy (NIFL) in complex upper urinary tract reconstructions surgery. METHODS: This was a retrospective study of 7 patients who underwent complex surgeries of ureteral reconstruction between May 2019 and October 2019. There were 6 males and 1 female with the age ranging from 24 to 57 years (median age was 47 years). There were 5 cases of right ureteral strictures, of which 3 were proximal ureteral strictures and 2 were multiple and long ureteral strictures caused by radiotherapy. There were 2 cases of left ureteral strictures, of which 1 was ureteropelvic junction stricture and 1 was proximal ureteral stricture. There were 4 cases of secondary repair operations and 3 cases of primary operations. All the patients underwent laparoscopic surgery via the abdominal approach. ICG was injected into the ureter via nephrostomy tube during the operations, and the diseased ureter was identified by NIFL. Among the patients, 2 cases underwent IUPU (Institute of Urology, Peking University) modified ileal ureter replacement, 2 cases underwent ureteroureterostomy, 2 cases underwent appendiceal onlay flap ureteroplasty, and 1 case underwent lingual mucosa onlay flap ureteroplasty. RESULTS: All the operations were successfully completed without open conversion. The localization and separation of ureteral lesions were completed under NIFL. The mean operative time was 187 (135-300) min. The duration of ureteral separation was 15-27 min, and the mean time was 18 min. The estimated blood loss was 15-200 mL, the mean estimated blood loss was 50 mL. There was one patient with ileal ureter replacement who had fever after surgery and responded well to antibiotics. The mean (range) length of postoperative hospital stay was 7 (6-10) days and no postoperative complications of a high grade (Clavien-Dindo Ⅲ and Ⅳ) occurred. Up to now, the mean follow-up duration was 9 (6-11) months, and no indocyanine green toxicity occurred. All D-J stents and nephrostomy were removed successfully 2 months after the operation. Ultrasound showed no obvious hydronephrosis, and CTU (computed tomography urography) showed that the urinary tract was unobstructed and the kidney function was normal. CONCLUSION The application of ICG in the complex upper urinary tract reconstructive surgery is a safe and easy method to help surgeon to identify the ureter which may reduce the risk of iatrogenic damage and protect the ureteral blood supply.
Adult ; Female ; Humans ; Indocyanine Green ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Ureter/surgery* ; Ureteral Obstruction ; Urologic Surgical Procedures ; Young Adult

OBJECTIVE: To investigate the value of preoperative three-dimensional image reconstruction in the treatment of ureteropelvic junction obstruction (UPJO). METHODS: We reviewed data on 40 patients (22 male cases, and 18 female cases) diagnosed with UPJO in Peking University First Hospital from May 2017 to April 2019. The median age was 26.5 years (IQR 23.25-38.75) years. There were 11 patients complicated with ectopic vessels, 14 patients with kidney stones, 3 patients with horseshoe kidney, and 6 patients with obstruction after pyeloplasty. All the patients underwent preoperative enhanced CT scan, and the CT data were reconstructed into three-dimensional image models. The obstruction position of ureteropelvic junction and the relationship between ureteropelvic junction and blood vessels and organs were observed by three-dimensional models to assist planning surgery. Thirty-seven patients underwent laparoscopic pyeloplasty (including 3 cases combined with pyelolithotomy with flexible cystoscope, 1 case combined with pyelolithotomy by sun-style cystoscope, 1 case with laparoscopic ureter resection and anastomosis, 3 cases of laparoscopic pyeloplasty of horseshoe kidney), 2 patients underwent laparoscopic ventral onlay lingual mucosal graft ureteroplasty, and 1 patient underwent robot-assisted laparoscopic pyeloplasty. RESULTS: Three-dimensional CT image clearly showed the relationship between the obstruction of ureteropelvic junction and blood vessels and organs after three-dimensional reconstruction. The type, diameter, position and direction of the ectopic vessels could be observed clearly before operation according to the three-dimensional reconstruction model, and the number, size, location and shape of renal calculi or other masses, the number of involved renal calyces and the anatomical distribution in the renal pelvis and calyces could be also evaluated preoperatively. After comprehensive analysis of the above information, individualized operation plans were performed on the patients, all the 40 cases were successfully completed with the surgery without any transfer to open surgery. The average operative time was (129.91±37.90) min (range: 75 to 273), the average blood loss was (48.1±78.0) mL (range: 10 to 400), the average hospitality was (5.04±1.99) d (range: 2 to 10), and the average postoperative drainage time was (3.8±1.4) d (range: 2 to 8). CONCLUSION The preoperative three-dimensional image reconstruction has a high clinical value in the treatment of ureteropelvic junction obstruction, and it is of great help to assist surgery planning and is worthy of further clinical promotion and application.
Adult ; Female ; Humans ; Imaging, Three-Dimensional ; Kidney Pelvis ; Laparoscopy ; Male ; Retrospective Studies ; Treatment Outcome ; Ureteral Obstruction/diagnostic imaging* ; Urologic Surgical Procedures ; Young Adult