Persistent inflammation plays a pivotal role in the initiation and progression of renal fibrosis. Activation of the pattern recognition receptor retinoic acid-inducible gene-I (RIG-I) is implicated in the initiation of inflammation. This study aimed to investigate the upstream mechanisms that regulates the activation of RIG-I and its downstream signaling pathway. Eight-week-old male C57BL/6 mice were used to establish unilateral ureteral obstruction (UUO)-induced renal fibrosis model, and the renal tissue samples were collected 14 days later for analysis. Transforming growth factor-β (TGF-β)-treated mouse renal tubular epithelial cells were used in in vitro studies. The results demonstrated that, compared to the control group, UUO kidney exhibited significant fibrosis, which was accompanied by the increases of RIG-I, p-NF-κB p65 and inflammatory cytokines, such as TNF-α and IL-1β. Additionally, the protein level of the E3 ubiquitin ligase RNF125 was significantly downregulated and predominantly localized in the renal tubular epithelial cells. Similarly, the treatment of tubular cells with TGF-β induced the increases in RIG-I, p-NF-κB p65 and inflammatory cytokines while decreasing RNF125. Co-immunoprecipitation (Co-IP) assays confirmed that RNF125 was able to interact with RIG-I. Overexpression of RNF125 promoted the ubiquitination of RIG-I, and accelerated its degradation via the ubiquitin-proteasome pathway. Overexpression of RNF125 in UUO kidneys and in vitro tubular cells effectively mitigated the inflammatory response and renal fibrosis. In summary, our results demonstrated that the decrease in RNF125 under pathological conditions led to reduction in RIG-I ubiquitination and degradation, activation of the downstream NF-κB signaling pathway and increase in inflammatory cytokine production, which promoted the progression of renal fibrosis.
Animals ; Fibrosis ; Male ; Ubiquitination ; Mice ; Mice, Inbred C57BL ; DEAD Box Protein 58 ; Ubiquitin-Protein Ligases/physiology* ; Inflammation/metabolism* ; Ureteral Obstruction/complications* ; Kidney/pathology* ; Signal Transduction ; Transforming Growth Factor beta/pharmacology*

OBJECTIVE: To investigate the clinical features and outcome of hydronephrosis induced by retroperitoneal fibrosis (RPF), and to evaluate the effect of corticosteroid based therapy combined with surgical intervention of ureteral obstruction. METHODS: A total of 17 RPF patients with hydronephrosis hospitalized in Peking University International Hospital from May 2016 to December 2019 were analyzed retrospectively. RESULTS: The median age was 56 (53, 65) years, the male to female ratio was 2.4 : 1, and the disease duration was 4.00 (0.83, 8.00) months. The initial symptoms included back pain (9 cases), abdominal pain (6 cases), oliguria (2 cases) and lower limb edema (3 cases). Eight patients presented left hydronephrosis, 1 right hydronephrosis and 8 bilateral hydronephrosis. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were both elevated in 13 patients (76.5%, n=17). Immunoglobin (Ig) G4 increased in 5 cases (29.4%, n=17). IgG, IgE and IgA increased in 4 cases (30.8%, n=13), 4 cases (30.8%, n=13) and 1 case (7.7%, n=13), respectively. Among 12 patients who underwent biopsy, 3 patients were diagnosed with IgG4-relate disease. The level of IgG4 in the tissues varied, 6 cases expressed less than 10 per high power field (HPF) or no expression (50.0%). Only 2 cases expressed 10-30/HPF (16.7%), and 4 cases revealed more than 30/HPF (33.3%). Among the 17 patients with ureteral obstruction, no urinary drainage procedure was needed in 4 patients who had mild ureteral obstruction, whereas, ureteral stenting was carried out in the other 13 cases before drug treatment. Time was too short to evaluate the effect of urinary drainage procedures in 4 patients. For the rest, ureterolysis had to be performed in 3 cases after failed ureteral stent insertion. Successful drain removal was accomplished in all of these 9 patients and the mean time to drain removal was (6.7±3.0) months. In addition, 10 patients had complete medical records after an average follow-up time of 5 (3-13) months. Levels of ESR, CRP, IgG4, IgG, IgE, IgA were 54.0 (36.3, 98.5) mm/h, 26.8 (8.7, 53.0) mg/L, 1.34 (0.55, 3.36) g/L, 16.3 (13.0, 21.1) g/L, 40.5 (31.4, 203.0) IU/mL, 2.51 (1.82, 3.25) g/L at baseline, which all decreased predominantly after treatment. ESR, CRP, IgG4, IgG, IgE and IgA dropped by 38.5 (23.5, 54.3) mm/h (P < 0.01), 23.0 (5.5, 52.0) mg/L (P < 0.05), 0.92 (0.40, 2.85) g/L (P < 0.01), 6.5 (1.7, 9.1) g/L (P < 0.05), 23.7 (4.8, 162.0) IU/mL (P < 0.05) and 0.77 (0.32, 1.26) g/L (P < 0.05), respectively. Size of mass measured by CT/MRI imaging became smaller significantly and hydronephrosis relieved. CONCLUSION Onset of RPF is insidious and lack of specific initial symptoms. Corticosteroid based therapy combined with surgical intervention of relieving obstruction is effective.
Aged ; Female ; Humans ; Hydronephrosis/etiology* ; Male ; Retroperitoneal Fibrosis/complications* ; Retrospective Studies ; Ureter ; Ureteral Obstruction

OBJECTIVE: To observe the protective effects of epalrestat (EPS) on interstitial fibrosis in unilateral ureteral obstruction (UUO) rats and its mechanism. METHODS: Rats were randomly divided into four groups: sham group, UUO group, UUO + epalrestat (50 or 100 mg/kg), 8 rats in each group.Rats in UUO and UUO + epalrestat group were obstructed left ureter.In the sham group, rats had their left ureters exposed and manipulated without ligation.Animals for epalrestat treatment received daily drug via gavage for 3 weeks, the rats of sham and UUO groups received equal amount of sodium carboxymethyl cellulose with the same regimen.Renal tissues pathological changes and collagen deposition were observed by HE and Masson's staining.The aldose reductase(AR) expression in renal tissues was measured by immunohistochemisty.The expression levels of collagen I, collagen III, alpha-smooth muscle actin (α-SMA), fibroblast-specific protein1 (FSP-1), fibronectin (FN), epithelial cadherin (E-cadherin), transforming growth factor-β1 (TGF-β1) and AR from kidney tissues were measured by real-time RT-PCR or Western blot. RESULTS: Compared with the sham group, the renal tissues of the UUO group showed significant fibrosis, including renal tubular epithelial cell atrophy and vacuolated degeneration, collagen deposition, fibroblasts and myofibroblasts proliferation and inflammatory cell infiltration, and concomitantly with the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably up-regulated, but E-cadherin was significantly reduced in UUO group.Compared with the UUO group, after 3 weeks epalrestat administration, the level of renal interstitial fibrosis was obviously ameliorated and the expressions of collagen I, collagen III, TGF-β1, AR, α-SMA, FSP-1 and FN were remarkably down-regulated, but E-cadherin was significantly increased in rats of epalrestat groups. CONCLUSION These results suggest that epalrestat attenuates renal interstitial fibrosis possibly through inhibition of EMT via inhibiting TGF-β1 and AR expression.
Animals ; Enzyme Inhibitors ; pharmacology ; Fibrosis ; complications ; drug therapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rhodanine ; analogs & derivatives ; pharmacology ; Thiazolidines ; pharmacology ; Ureteral Obstruction ; complications ; drug therapy

OBJECTIVE: To explore the effect of telmisartan on the expression of metadherin in the kidney of mice with unilateral ureter obstruction. METHODS: Eighteen male C57 mice were randomized into sham-operated group, model group and telmisartan treatment group. In the latter two groups, renal interstitial fibrosis as the result of unilateral ureter obstruction (UUO) was induced by unilateral ureteral ligation with or without telmisartan intervention. Renal pathological changes of the mice were assessed using Masson staining, and immunohistochemistry and Western blotting were used to detect the expression of extracellular matrix proteins and metadherin in the kidney of the mice. In the experiment, cultured mouse renal tubular epithelial cells (mTECs) were stimulated with transforming growth factor-β1 (TGF-β1) and transfected with a siRNA targeting metadherin, and the changes in the expressions of extracellular matrix proteins and metadherin were detected using Western blotting. RESULTS: The expressions of extracellular matrix proteins and metadherin increased significantly in the kidney of mice with UUO ( < 0.05). Intervention with telmisartan significantly lowered the expressions of extracellular matrix proteins and metadherin and alleviated the pathology of renal fibrosis in mice with UUO ( < 0.05). In cultured mTECs, siRNA-mediated knockdown of metadherin obviously reversed TGF-β1-induced increase in the expressions of extracellular matrix proteins and metadherin. CONCLUSIONS Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice.
Angiotensin II Type 1 Receptor Blockers ; Animals ; Antihypertensive Agents ; Extracellular Matrix Proteins ; metabolism ; Fibrosis ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Small Interfering ; Random Allocation ; Telmisartan ; pharmacology ; Transforming Growth Factor beta1 ; pharmacology ; Ureteral Obstruction ; complications ; metabolism

To isolate bone marrow mesenchymal stem cells (BM-MSCs) and establish the model of chronic kidney disease (CKD) of Wuzhishan (WZS) mini-pig, and to study the repairment effect of BM-MSCs on CKD-induced renal fibrosis in vitro.
 Methods: Density gradient method was used to isolate and culture BM-MSCs. The cells were verified by morphology, phenotype, differentiation and so on. The left partial ureteral obstruction (LPUUO) was used to establish the CKD model, which was evaluated by B-ultrasound, single-photon emission computed tomography (SPECT), HE and Masson staining. The cells were divided into 3 groups, the tissue plus BM-MSCs group, the tissue group, and the BM-MSCs group, respectively. Seven days later, the supernatants were collected to observe the changes of hepatocyte growth factor (HGF) cumulative release. HE and Masson staining was used to observe the changes of renal tissue.
 Results: The isolated BM-MSCs possessed the features as follow: fibroblast-like adherent growth; positive in CD29 and CD90 expression while negative in CD45 expression; osteogenic induction and alizarin red staining were positive; alcian blue staining were positive after chondrogenic induction. Twelve weeks after the operation of LPUUO, B-ultrasound showed the thin renal cortical with pelvis effusion; SPETCT showed the left kidney delayed filling and renal impairment. The accumulation of HGF in the tissue plus BM-MSCs group was significantly higher than that in the tissue alone group at the 1st, 5th, 6th, 7th day, respectively (P<0.05). HE staining showed the different degree of renal lesions between the tissue plus BM-MSCs+CKD group and the tissue alone group, which was aggravated with the time going. Masson staining showed that the cumulative optical density of blue-stained collagen fibers in tissue plus BM-MSCs group was significantly lower than that in the tissue group at the 5th to 7th day (P<0.05).
 Conclusion: BM-MSCs from WZS mini-pig can inhibit or delay the progress of CKD-induced renal fibrosis through autocrine HGF in vitro.
Animals ; Autocrine Communication ; physiology ; Bone Marrow Cells ; Cells, Cultured ; Fibrosis ; physiopathology ; prevention & control ; Hepatocyte Growth Factor ; metabolism ; Kidney ; drug effects ; pathology ; physiopathology ; Mesenchymal Stem Cells ; drug effects ; Renal Insufficiency, Chronic ; complications ; physiopathology ; Swine ; Swine, Miniature ; Ureteral Obstruction ; complications

PURPOSE: To evaluate changes in differential renal function (DRF), as a functional outcome, in children who underwent redo pyeloplasty for management of failed pyeloplasty and to examine the factors that affect functional outcomes. MATERIALS AND METHODS: Between January 2002 and November 2010, a total of 18 patients who underwent redo pyeloplasty for persistent ureteropelvic junction obstruction after failed pyeloplasty were enrolled in this study. We assessed perioperative factors and evaluated changes in renal cortical thickness (RCT), renal function, and hydronephrosis by use of serial ultrasound and diuretic renography. RESULTS: The mean follow-up period was 44.83+/-28.86 months. After redo pyeloplasty, prevention of further functional deterioration was observed in only 12 of the 18 patients. After dividing the patients according to this observation, we discovered significant differences in both change in DRF (dDRF) and change in RCT (dRCT) (difference between before and after initial pyeloplasty) between the two groups (p<0.001). Additionally, we noted a significant positive correlation between dRCT and dDRF. All patients showed improvements in hydronephrosis grade and relief of symptoms compared with before redo pyeloplasty. CONCLUSIONS: Redo pyeloplasty should be considered in cases of failed pyeloplasty to preserve renal function and obtain relief from symptoms. If patients show severe deterioration of DRF or a decrease in RCT after initial pyeloplasty, preservation of DRF in these patients after redo pyeloplasty could be difficult. Therefore, redo pyeloplasty should be performed before severe deterioration of DRF or decrease in RCT.
Adolescent ; Child ; Child, Preschool ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Hydronephrosis/etiology/ultrasonography ; Infant ; Kidney/*physiopathology/ultrasonography ; Kidney Cortex/pathology ; Kidney Function Tests/methods ; Kidney Pelvis/*surgery/ultrasonography ; Male ; Postoperative Period ; Prognosis ; Reoperation/adverse effects/methods ; Retrospective Studies ; Treatment Failure ; Treatment Outcome ; Ureteral Obstruction/complications/pathology/*surgery ; Ureteral Obstruction/*surgery

Aged ; Female ; Humans ; Kidney Pelvis ; pathology ; surgery ; Rupture, Spontaneous ; diagnosis ; etiology ; surgery ; Ureteral Calculi ; complications ; diagnosis ; surgery ; Ureteral Obstruction ; complications ; diagnosis ; surgery

OBJECTIVETo demonstrate the effects and mechanisms of Qifu decoction( QFD) on renal interstitial fibrosis (RIF) in model rats with yang-deficiency syndrome.

METHODThe rats were randomly divided into 3 groups, the Sham group (Group A), the Model group (Group B), the Qifu decoction group (Group C) and the Enalapril group (Group D). The RIF model was established by adenine administrated and unilateral ureteral obstruction (UUO) of the left ureter. After the model was successfully established, the rats in Group C and D were administrated with QFD or the Enalapril suspension,while the rats in Group A and B were administrated with distilled water. All rats were administrated for 3 weeks. Before administration and at the end of week 1, 2 and 3, the rats were weighted, and 24 h urinary protein excretion (Upro), urinary β2-microglobulin (Uβ2-MG) and urinary N-acetyl-D-glucosaminidase (NAG) were examined, respectively. All rats were killed after administration for 3 weeks. Blood and renal tissues were collected, renal morphology and tubulointerstitial morphology were evaluated, respectively. Serum cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), blood urea nitrogen (BUN), serum creatinine (Scr) and uric acid (UA) were detected, respectively. The protein expressions of E-cadherin, α-smooth muscle actin(α-SMA), transforming growth factor-β1 (TGF-β1), onnective tissue growth factor (CTGF) extracellular signal-regulated protein kinase 1/2(ERK1/2) and phosphorylated-ERK1/2 (p-ERK1/2) in kidney were evaluated, respectively.

RESULTQFD ameliorated serum cAMP level and the rate of cAMP/cGMP, attenuated urinary β2-MG level, NAG level and renal tubulointerstitial fibrosis, increased E-cadherin protein expression, and reduced α-SMA, TGF-β1, CTGF and p-ERK1/2 protein expressions in the kidney. However, QFD had no influence on renal function in vivo. In addition, these effects were better than those of the model rats treated by Enalapril.

CONCLUSIONQFD could alleviate yang-deficiency parameters, as well as urinary β2-MG level and NAG level in model rats induced by adenine administration and UUO. Moreover, QFD could improve EMT and RIF by up-regulating E-cadherin protein expression, and down-regulating α-SMA, TGF-β1, CTGF and p-ERK1/2 protein expressions, the key molecular in ERK1/2 signaling pathway.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Extracellular Signal-Regulated MAP Kinases ; antagonists & inhibitors ; Fibrosis ; Kidney ; drug effects ; pathology ; Kidney Diseases ; drug therapy ; pathology ; MAP Kinase Signaling System ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Ureteral Obstruction ; complications ; Yang Deficiency ; complications

OBJECTIVETo compare clinical outcomes of three dimensional (3D) and traditional two dimentional (2D) laparoscopic pyeloplasty for ureteropelvic junction obstruction (UPJO).

METHODSClinical data on 31 patients who underwent retroperitoneoscopic pyeloplasty for UPJO in Peking Union Medical Hospital from January 2013 to March 2014 were retrospectively analyzed. There were 16 male and 15 female patients, and the age ranged from 21 to 42 years, mean (30 ± 6) years. The lesions of 20 cases were located on the left side and 11 cases on the right side. All cases were diagnosed as UPJO by B ultrasound and computed tomography urography (CTU). According to 3D or 2D laparoscopy, these patients were divided into two groups. The 3D laparoscopy group included 16 cases, who received 3D retroperitoneoscopic pyeloplasty. The 2D laparoscopy group included 15 cases, who received traditional 2D retroperitoneoscopic pyeloplasty. Demographic data (gender, age, laterality, body mass index), perioperative indexes and clinical outcomes (operative time, estimated blood loss , postoperative hospital stay, total hospitalization charge) were collected and compared between two groups.Numerical demographic and perioperative data were analyzed by using Student's t-test. Categorical data were compared using Pearson's Chi-square test.

RESULTSAll operations were completed successfully without open convertion.In the 3D laparoscopy group operative time was significantly shorter than 2D laparoscopy group ((106 ± 16) minutes vs. (124 ± 24) minutes, t = 5.993, P = 0.021) . There were no significant difference between two groups on the estimated blood loss ((54 ± 14) ml vs. (57 ± 16) ml, t = 0.285, P = 0.598), postoperative hospital stay ((7.3 ± 0.7) days vs. (7.5 ± 0.6) days, t = 1.415, P = 0.244), incidence of postoperative complications (0/16 vs. 1/15, χ(2) = 1.102, P = 0.484) and total hospitalization charge ((25 687 ± 3 032) RMB vs. (25 426 ± 2 626) RMB, t = 0.065, P = 0.800) . All patients were followed up from 3 to 12 months (mean 6 months).Ureteropelvic junction stricture recurred in 2 cases respectively from 3D laparoscopic group and traditional laparoscopic group. Both were cured.

CONCLUSIONS3D laparoscopic pyeloplasty is safe and feasible. Compared with the traditional 2D laparoscopic technology, 3D laparoscopy technology reduces the operation difficulty and shortens the operative time.

Adult ; Chi-Square Distribution ; Female ; Humans ; Hydronephrosis ; congenital ; surgery ; Imaging, Three-Dimensional ; Kidney Pelvis ; Laparoscopy ; methods ; Length of Stay ; Male ; Multicystic Dysplastic Kidney ; surgery ; Operative Time ; Postoperative Complications ; Recurrence ; Retrospective Studies ; Treatment Outcome ; Ureteral Obstruction ; surgery ; Urologic Surgical Procedures ; methods ; Young Adult

Crossed fused renal ectopia is a rare anomaly and may be associated with pelvic ureteric junction obstruction (PUJO). The L-shaped fusion variety is even rarer. We report such a case with a crossed fused ectopic pelvic kidney (L-type) with PUJO and its successful laparoscopic management. Through this report we emphasize the importance of adequate preoperative imaging and intraoperative details to avoid mishaps.
Adolescent ; Female ; Humans ; Kidney/*abnormalities ; Kidney Diseases/*complications/congenital/surgery ; Kidney Pelvis/*surgery ; Laparoscopy/*methods ; Reconstructive Surgical Procedures/*methods ; Ureter/*surgery ; Ureteral Obstruction/etiology/*surgery ; Urologic Surgical Procedures/methods