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Obstructed urine flow is known to cause structural and functional kidney damage leading to renal fibrosis. However, limited information is available on the change in kidney lipids during urinary tract obstruction. In this study, we investigated the change in lipidome in a mouse model with unilateral ureteral obstruction (UUO). The establishment of the UUO model was confirmed by histopathological examination using transmission electron microscopy. Untargeted liquid chromatography/mass spectrometry was carried out over a time course of 4 and 7 days. Compared to the sham control, the UUO kidney at 7 days showed dilatation of the renal tubule with loss of brush borders and thickening of the capillary endothelium. In the kidney lipidomes obtained from the UUO 7 days group compared to the control, a significant decrease of ceramide, sphingomyelin, phosphatidylcholine, lysophospholipids, and phosphatidylethanolamine was observed, whereas cholesteryl esters, free fatty acids, phosphatidylglycerol, and cardiolipins were significantly increased. The present study revealed the disturbed lipid metabolism in the UUO model, which may provide a clue to potential lipid pathways and therapeutic targets for the early stage of renal fibrosis.
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Modelos Animales de Enfermedad , Riñón , Metabolismo de los Lípidos , Lipidómica , Obstrucción Ureteral , Animales , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patología , Lipidómica/métodos , Ratones , Riñón/metabolismo , Riñón/patología , Masculino , Fibrosis , Ratones Endogámicos C57BLRESUMEN
INTRODUCTION: Inflammatory and immunological responses are reported involved in the pathogenesis and progression of obstructive nephropathy (ON). This study was designed to investigate the characteristics of peripheral immunity in patients with upper urinary tract urolithiasis and analyze the underlying associations with renal function. METHODS: Patients with unilateral upper urinary tract urolithiasis meeting the operation indications were prospectively enrolled. Preoperative circulating immune cells and inflammatory cytokines were detected in our clinical laboratory, and the indicators of renal function and calculi related parameters were particularly recorded. Patients were sectionalized into subgroups on the basis of the lesion of calculi. Characteristics of peripheral immunity in each subgroup were investigated by statistical approaches, and the underlying correlations with the degree of hydronephrosis (HN) and renal function were discussed in corresponding group. RESULTS: Patients with ureteral calculi presented severer HN compared with renal calculi, especial middle ureteral calculi, acting as the chief culprit of ON, exhibiting the highest serum creatine and blood urea nitrogen, most impaired estimated glomerular filtration rate, and severest HN. In addition, serum interleukin-8 (IL-8) and IL-6 were demonstrated presenting statistical differences between ureteral calculi and renal calculi patients, exhibiting underlying values in comprehending ON. However, circulating immune cells were demonstrated no obvious differences among groups. CONCLUSIONS: Circulating inflammatory cytokines, referred in particular to serum IL-8 and IL-6 were partially associated with kidney injury in patients with upper urinary tract urolithiasis. But the specific influences and mechanisms between them needed to be investigated furthermore.
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Cálculos Ureterales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Cálculos Ureterales/inmunología , Cálculos Ureterales/complicaciones , Adulto , Estudios Prospectivos , Cálculos Renales/inmunología , Riñón/inmunología , Riñón/fisiopatología , Hidronefrosis/sangre , Hidronefrosis/etiología , Hidronefrosis/inmunología , Urolitiasis/inmunología , Citocinas/sangre , Anciano , Estudios TransversalesRESUMEN
Objective: Secondary pyeloplasty for recurrent ureteropelvic junction obstructions may be a safe and feasible surgical option for patients. This study aimed to demonstrate outcomes of utilizing a non-transecting buccal mucosa graft ureteroplasty for management of recurrent ureteropelvic junction obstruction after prior failed pyeloplasty. Methods: We performed a retrospective review of our Collaborative of Reconstructive Robotic Ureteral Surgery database for all consecutive patients who underwent buccal mucosa graft ureteroplasty between April 2012 and June 2022 for management of recurrent ureteropelvic junction obstructions after prior failed pyeloplasty. The primary outcome included surgical success which was defined as the absence of flank pain and no obstruction on imaging. Results: Overall, ten patients were included in our analysis. The median stricture length was 2.5 (interquartile range [IQR] 1.8-4.0) cm. The median operative time was 230.5 (IQR 199.5-287.0) min and median estimated blood loss was 50.0 (IQR 28.8-102.5) mL. At a median follow-up of 10.3 (IQR 6.2-14.8) months, 80% of patients were surgically successful and there were no major (Clavien-Dindo Grade>2) complications. Conclusion: Buccal mucosa graft ureteroplasty is a valuable non-transecting surgical option for patients with recurrent ureteropelvic junction obstructions who failed prior pyeloplasty and has comparable outcomes to the literature regarding standard transecting techniques.
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Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts, often misdiagnosed due to its similarity to many infectious and non-infectious diseases. This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics, including methotrexate, leflunomide, and infliximab, leading to recurrent joint pain, poorly controlled rheumatoid arthritis activity, and persistent elevation of white blood cell counts. Abdominal CT revealed a pelvic mass and right ureteral dilation. Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules, indicating actinomycosis. The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide, hydroxychloroquine sulfate, and tofacitinib, resulting in improved joint symptoms and normalized white blood cell counts. After 2 years of follow-up, the patient remained stable with no recurrence. This case highlights the importance of clinicians being vigilant for infections, particularly chronic, occult infections from rare pathogens, in rheumatoid arthritis patients on potent immunosuppressants and biologics, advocating for early screening and diagnosis.
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Actinomicosis , Artritis Reumatoide , Obstrucción Ureteral , Humanos , Femenino , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Persona de Mediana Edad , Actinomicosis/diagnóstico , Actinomicosis/complicaciones , Actinomicosis/tratamiento farmacológico , Obstrucción Ureteral/etiología , Inmunosupresores/uso terapéuticoRESUMEN
Case summary: A 5.5-year-old male neutered domestic shorthair cat was presented with a 2-year history of progressive chronic kidney disease. Abdominal ultrasonography revealed bilateral chronic renal degeneration, nephrolithiasis, cortical hyperechogenicity and infarction. Left orthotopic renal transplantation was performed using the Synovis vascular coupling system for end-to-end anastomosis of the renal arteries and veins. Two months after transplantation, renal values were elevated, and abdominal ultrasonography revealed hydronephrosis and hydroureter of the transplanted kidney. Fluoroscopic antegrade pyelography identified a proximal ureteral stricture. Proximal neoureterocystostomy was performed and renal values normalized postoperatively. The cat was re-evaluated for acute stranguria and severe azotemia 12 months later. Contrast-enhanced CT revealed severe hydronephrosis of the transplanted kidney, obstruction of the proximal ureter and adhesions to the urinary bladder. Upon exploration, retroperitoneal fibrosis was found covering the transplanted kidney. Given the clinical situation, a subcutaneous ureteral bypass device (SUB) was placed. Clinicopathologic analyses, trough cyclosporine levels, aerobic urine cultures and ultrasonographic evaluations of the transplanted kidney were monitored every 1-3 months. Patency of the SUB was reassessed every 3-6 months. At 15 months after placement, the SUB occluded due to kinking of the cystostomy catheter and was replaced. At 28 months after SUB placement, renal function and clinical status deteriorated, and the cat was euthanized. Relevance and novel information: To the authors' knowledge, this is the first report of a SUB device being used for management of ureteral obstruction in a transplanted kidney in a cat.
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Introduction: Rectus sheath hematomas (RSHs) can occur from the rupture of the epigastric arteries, leading to blood accumulation within the rectus abdominis sheath. Herein, we report the unique case of an RSH resulting in acute ureteral obstruction, which was associated with the use of a handheld deep-tissue percussive massage device in attempts to relieve abdominal pain. Case Report: A morbidly obese man in his late 50s was admitted with complications of COVID-19, including acute respiratory syndrome, bilateral peroneal deep vein thromboses, and acute kidney injury. He was treated with anticoagulants (subcutaneous enoxaparin and apixaban), dexamethasone, and remdesivir. He developed severe abdominal pain, and a large (14 × 17 cm) right rectus sheath and an extraperitoneal pelvic hematoma were identified by computed tomography. The hematoma extended across the midline into the left pelvis and the retroperitoneum with associated mild right hydronephrosis. A handheld percussive massage device (Theragun®) was applied repeatedly at the site of enoxaparin injection into the abdominal wall in attempts to alleviate the pain. On day 12, bilateral nephrostomy tubes were inserted. A nephrostogram revealed mild hydroureteronephrosis to the ureterovesicular junction bilaterally and extrinsic compression of the bladder. On day 17, the patient suffered a cardiac arrest and died. Conclusion: This case report offers insights into the pathophysiology of obstructive uropathy and is a reminder of the importance of considering uncommon causes of obstructive uropathy in the diagnosis and management of AKI, particularly in hospitalized patients receiving anticoagulation. We know of no previous reference of obstructive uropathy caused by retroperitoneal hematoma associated with the use of a portable massage device applied to the abdominal wall.
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OBJECTIVE: To explore the clinical safety and effectiveness of self-draining ureteral stent with thread in kidney transplant recipients in renal transplantation. METHODS: This study is a prospective cohort clinical study in the Department of Urology of Peking University People's Hospital from November 2022 to January 2024. The ureteral stent with thread group, in which a 2-0 Mersilene suture of 20-30 cm was used at the bladder end of the ureteral stent during the operation. On the 9th day after the operation, the suture attached to the end of the ureteral stent was expelled out of the urethral orifice with the urine when the catheter was removed. The ureteral stent could be removed along with the suture. As to the cystoscope group, a ureteral stent was routinely placed during kidney transplantation, and the ureteral stent was removed under local infiltration anesthesia through cystoscopy after the operation. The pain scores [numerical rating scale (NRS)-11] during catheter removal and the incidence of urinary tract infections were observed and compared between the two groups. t test was used to compare the pain scores of indwelling ureteral stents and ureteral stents removal between the two groups, and Chi-square test was used to compare the occurrence of urinary system complications within 3 months after operation between the two groups. P < 0.05 was considered statistically significant. RESULTS: As of March 2024, all the recipients were followed up for an average of 6 months (3 to 12 months) postoperatively. A total of 46 kidney transplantation patients were included, with 21 in the ureteral stent with thread group and 25 in the cystoscope group. There were no statistically significant differences between the two groups in age distribution, male-to-female ratio, and deceased versus live donor grafts. Three months after renal transplantation, there were 15 cases of urinary tract infection in the cystoscope group and 4 cases in the ureteral stent with thread group (P=0.007). No significant urinary fistula, wound infection, or ureteral stenosis occurred in either group. No stent-related complications, stent migration, or stone formation were observed. The postoperative bladder spasm symptom scores for indwelling ureteral stents in the cystoscope group and the ureteral stent with thread group were 4.4±2.5 and 4.6±2.4, respectively, with no statistically significant difference (t=0.29, P=0.773). However, the pain scores during ureteral stent removal were 4.9±1.6 and 3.0±1.0 in the two groups, respectively, with a statistically significant diffe-rence (t=5.017, P < 0.001). The total costs of indwelling and removing ureteral stents in the cystoscopy group and the ureteral stent with thread group were 6 452.0 (5 539.5, 6 452.0) yuan and 3 225.0 (3 225.0, 3 225.0) yuan, respectively, and the difference was statistically significant (P < 0.001). CONCLUSION: Compared with the conventional transplanted kidney ureteral stent, the self-discharge ureteral stent technique with sutures is simpler, has a shorter ureteral stent inlay time, reduces the symptoms of bladder spasms, significantly reduces the cost of catheterization, and has fewer postoperative urinary system complications. It is a worthy improved surgical method to be promoted.
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Trasplante de Riñón , Stents , Uréter , Humanos , Trasplante de Riñón/efectos adversos , Stents/efectos adversos , Uréter/cirugía , Estudios Prospectivos , Femenino , Masculino , Infecciones Urinarias/etiología , Infecciones Urinarias/prevención & control , Suturas , Persona de Mediana EdadRESUMEN
Renal fibrosis is the common endpoint of nearly all chronic and progressive nephropathies. Cell death and sterile inflammation are the main characteristics of renal fibrosis, which can lead to end-stage renal failure. The inflammatory reaction triggered by tissue damage is strongly related to necroptosis, a type of caspase-independent, regulated cell death. Using an animal model of unilateral ureteral obstruction (UUO), the anti-fibrotic effects of sorafenib (SOF), a multi-kinase inhibitor, and edaravone (EDV), a potent antioxidant and free radical scavenger, were examined in rats with obstructive nephropathy. Experimentally, animals were divided randomly into five groups: sham; UUO; UUO + SOF (5 mg/kg/day, P.O.); UUO + EDV (20 mg/kg/day, P.O.); and UUO + SOF + EDV groups. The kidney function biomarkers, oxidant/antioxidant status, renal mRNA expressions of TNF-α, collagen-1α, protein expressions of RIPK-1, RIPK-3, MLKL, caspase-8, HYP, MPO, and TNF-α were all significantly modulated by UUO. Administration of either SOF or EDV significantly attenuated cellular and molecular changes induced by UUO. Also, histopathological changes were improved. Moreover, SOF in combination with EDV, significantly improved UUO-induced renal fibrosis compared with each drug alone. Collectively, administration of either SOF or EDV or both of them significantly attenuated the rats with obstructive nephropathy, possibly by blocking the RIPK-3/MLKL necroptotic pathway and suppressing renal oxidative stress and inflammation.
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Background and Objectives: The European Association of Urology guidelines on urolithiasis highlight the limited evidence supporting the superiority of percutaneous nephrostomy (PCN) over retrograde ureteral stent placement for the primary treatment of infected hydronephrosis secondary to urolithiasis. We, therefore, conducted a systematic review and meta-analysis comparing the effects of PCN and retrograde ureteral stent in patients with severe urinary tract infections secondary to obstructive urolithiasis. Materials and Methods: Meta-analyses were performed to compare four outcomes: time for the temperature to return to normal; time for the white blood cell (WBC) count to return to normal; hospital length of stay; and procedure success rate. After a full-text review, eight studies were identified as relevant and included in our systematic review and meta-analysis. Results: No significant difference was detected between PCN and retrograde ureteral stenting for the time for the temperature to return to normal (p = 0.13; mean difference [MD] = -0.74; 95% confidence interval [CI] = -1.69, 0.21; I2 = 96%) or the time for the WBC count to return to normal (p = 0.24; MD = 0.46; 95% CI = -0.30, 1.21; I2 = 85%). There was also no significant difference between methods for hospital length of stay (p = 0.78; MD = 0.45; 95% CI = -2.78, 3.68; I2 = 96%) or procedure success rate (p = 0.76; odds ratio = 0.86; 95% CI = 0.34, 2.20; I2 = 47%). Conclusions: The clinical outcomes related to efficacy did not differ between PCN and retrograde ureteral stenting for severe urinary tract infection with obstructive urolithiasis. Thus, the choice between procedures depends mainly on the urologist's or patient's preferences.
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Nefrostomía Percutánea , Stents , Infecciones Urinarias , Urolitiasis , Humanos , Tiempo de Internación/estadística & datos numéricos , Nefrostomía Percutánea/métodos , Stents/efectos adversos , Resultado del Tratamiento , Urolitiasis/complicaciones , Urolitiasis/cirugíaRESUMEN
BACKGROUND: This study aims to describe a rare case of primary ureteral hemangiosarcoma, in which surgical intervention preserved the kidney and ureter after tumor removal. CASE PRESENTATION: A 13-year-old, neutered male dog, weighing 14 kg, mixed-breed, presented with apathy, anorexia, acute-onset vomiting, and abdominal discomfort during the physical examination. Ultrasonography and pyelography revealed a right-sided dilation of the renal pelvis and ureter due to complete obstruction in the middle third of the ureter. A mass obstructing the lumen of the right ureter was completely resected, and ureteral suturing was performed, preserving the integrity of the involved structures. Histopathology confirmed primary ureteral hemangiosarcoma. Due to the local and non-invasive nature of the mass, chemotherapy was not initiated. The patient's survival was approximately two years, and normal renal function was preserved throughout this period. CONCLUSIONS: Considering this type of tumor in the differential diagnosis of upper urinary tract obstructive disorders. Furthermore, the preservation of the ureter and kidney is a suitable therapeutic option after surgical resection of non-invasive tumors.
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Enfermedades de los Perros , Hemangiosarcoma , Neoplasias Ureterales , Animales , Masculino , Perros , Hemangiosarcoma/veterinaria , Hemangiosarcoma/complicaciones , Hemangiosarcoma/cirugía , Enfermedades de los Perros/cirugía , Neoplasias Ureterales/veterinaria , Neoplasias Ureterales/complicaciones , Neoplasias Ureterales/cirugía , Neoplasias Ureterales/patología , Paraplejía/veterinaria , Paraplejía/etiología , Paraplejía/cirugía , Obstrucción Ureteral/veterinaria , Obstrucción Ureteral/cirugíaRESUMEN
BACKGROUND: Varicocele embolization, a minimally invasive treatment for symptomatic varicoceles, carries a rare risk of complications like ureteral obstruction and hydronephrosis. This case report documents such a case to raise awareness of these potential complications and showcase minimally invasive surgical management as a successful solution. CASE SUMMARY: A 35-year-old male presented with flank pain and hematuria following varicocele embolization. Imaging confirmed left ureteral obstruction and hydronephrosis. Laparoscopic ureterolysis successfully removed the embolization coil and repaired the ureter, resolving the patient's symptoms. Follow-up at six months and two years showed sustained improvement. CONCLUSION: Minimally invasive surgery offers an effective treatment option for rare complications like ureteral obstruction arising from varicocele embolization.
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Case summary: A 9-year-old, spayed, female domestic shorthair cat presented with an open wound approximately 1 cm in size with exposure of the left subcutaneous ureteral bypass (SUB) shunting port that was placed approximately 11 months before presentation. Primary closures were attempted twice before local wound management with omentalisation and repositioning of the port. The exposed port was lavaged topically with a polyhexanide and propylbetaine wound irrigation solution before omentalisation and repositioning, resulting in successful retention of the implant. Five months after revision and omentalisation, there was complete coverage and healing of the wound. Relevance and novel information: Adequate topical treatment, repositioning and omentalisation could be a successful treatment option for the uncommon complication of SUB shunting port extrusion secondary to resistant local infection originating from the urinary tract.
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INTRODUCTION: The aim was to compare the efficacy of polyacrylate polyalcohol copolymer (PPC) injections and dextranomer/hyaluronic acid (Dx/Ha) injections for the endoscopic treatment of vesicoureteral reflux in children. MATERIAL: This retrospective cohort study included 189 young patients who had endoscopic treatment for vesicoureteral reflux from January 2012 to December 2019 in our center. Among them, 101 had PCC injections and 88 had Dx/Ha injections. Indications for treatment were vesicoureteral reflux with breakthrough urinary tract infection or vesicoureteral reflux with renal scarring on dimercaptosuccinic acid (DMSA) renal scan. Endoscopic injection was performed under the ureteral meatus. Early complications, recurrence of febrile urinary tract infection and vesicoureteral reflux after endoscopic injection, ureteral obstruction and reintervention were evaluated and compared between groups. RESULTS: Endoscopic treatment was successful in 90.1% of patients who had PPC injection and in 82% of patients who had Dx/Ha injection. Four patients presented a chronic ureteral obstruction after PPC injection, one with a complete loss of function of the dilated kidney. One patient in the Dx/Ha group presented a postoperative ureteral dilatation after 2 injections. CONCLUSION: Despite a similar success rate after PPC and Dx/Ha injections for endoscopic treatment of VUR, there may be a greater risk of postoperative ureteral obstruction after PPC injections. The benefit of using PPC to prevent febrile UTI and renal scarring in children with low-grade VUR does not seem to outweigh the risk of chronic ureteral obstruction.
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Dextranos , Ácido Hialurónico , Obstrucción Ureteral , Reflujo Vesicoureteral , Humanos , Reflujo Vesicoureteral/terapia , Estudios Retrospectivos , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/uso terapéutico , Ácido Hialurónico/efectos adversos , Femenino , Masculino , Dextranos/uso terapéutico , Dextranos/administración & dosificación , Dextranos/efectos adversos , Preescolar , Resultado del Tratamiento , Lactante , Resinas Acrílicas/uso terapéutico , Resinas Acrílicas/administración & dosificación , Niño , Inyecciones , Estudios de Cohortes , Ureteroscopía/efectos adversosRESUMEN
Objective: To systematically summarise the current clinical evidence for de novo malignant upper urinary tract obstruction treatment with a focus on standards of reporting, patient outcomes and future research needs. Methods: This review protocol was published via PROSPERO (CRD42022341588). OVID MEDLINE (R), EMBASE, Cochrane Central Register of Controlled Trials-CENTRAL were searched up to June 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses. Prospective and retrospective studies were included. Results: Of 941 articles identified, 82 with 8796 patients were eligible for inclusion.Most studies in the published literature are retrospective and investigate heterogenous malignancies. Percutaneous nephrostomy and ureteric stenting are the most studied interventions. Few studies describe the outcomes from no intervention or investigate patient perspectives. Overall reported median survival after intervention was around 11.7 months. A lack of standardised reporting of outcomes was evident. Conclusions: Malignant upper urinary tract obstruction is an important clinical condition affecting patients globally. Overall survival after intervention appears poor however the current evidence base has significant limitations due to studies of low methodological quality and the lack of a standardised framework for reporting outcomes.We have provided a pragmatic framework for future studies based on the review to ensure a uniform methodology is utilised moving forward.
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The long noncoding RNA growth arrest-specific 5 (lncRNA Gas5) is implicated in various kidney diseases. In this study, we investigated the lncRNA Gas5 expression profile and its critical role as a potential biomarker in the progression of chronic kidney disease. Subsequently, we assessed the effect of lncRNA Gas5 deletion on renal fibrosis induced by unilateral ureteral obstruction (UUO). The results indicated that loss of lncRNA Gas5 exacerbates UUO-induced renal injury and extracellular matrix deposition. Notably, the deletion of lncRNA Gas5 had a similar effect on control mice. The fibrogenic phenotype observed in mice lacking lncRNA Gas5 correlates with peroxisome proliferator-activated receptor (PPAR) signaling pathway activation and aberrant cytokine and chemokine reprogramming. Single-cell RNA sequencing analysis revealed key transcriptomic features of fibroblasts after Gas5 deletion, revealing heterogeneous cellular states suggestive of a propensity for renal fibrosis. Our findings indicate that lncRNA Gas5 regulates the differentiation and activation of immune cells and the transcription of key genes in the PPAR signaling pathway. These data offer novel insights into the involvement of lncRNA Gas5 in renal fibrosis, potentially paving the way for innovative diagnostic and therapeutic targets.
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Fibrosis , ARN Largo no Codificante , Análisis de la Célula Individual , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Animales , Fibrosis/genética , Ratones , Perfilación de la Expresión Génica , Masculino , Obstrucción Ureteral/patología , Obstrucción Ureteral/genética , Obstrucción Ureteral/metabolismo , Riñón/patología , Riñón/metabolismo , Transcriptoma , Transducción de Señal/genética , Ratones Endogámicos C57BL , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Receptores Activados del Proliferador del Peroxisoma/genética , Ratones Noqueados , Fibroblastos/metabolismo , Fibroblastos/patología , Enfermedades Renales/genética , Enfermedades Renales/patología , Enfermedades Renales/metabolismoRESUMEN
OBJECTIVEï¼To elucidate the mechanism by which Huoxue Jiedu Huayu recipe (, HJHR) regulates angiogenesis in the contralateral kidney of unilateral ureteral obstruction (UUO) rats and the mechanism by which it reduces of renal fibrosis. METHODS: Male Wistar rats were randomly divided into 4 groups: the sham group, UUO group (180 d of left ureter ligation), UUO plus eplerenone (EPL) group, and UUO plus HJHR group. After 180 d of oral drug administration, blood and contralateral kidneys were collected for analysis. Angiogenesis- and fibrosis-related indexes were detected. RESULTS: HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels of α-smooth muscle actin (α-SMA), vimentin and collagen I. Moreover, these treatments could reduce the expression of vascular endothelial growth factor-A (VEGFA) by inhibiting the infiltration of macrophages. Furthermore, HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production, which inhibited angiogenesis. Finally, the coexpressions of CD34, CD105 and α-SMA were decreased in the HJHR and EPL groups, indicating that endothelial-to-mesenchymal transition was inhibited. CONCLUSIONS: These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFA-induced angiogenesis, encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.
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Medicamentos Herbarios Chinos , Fibrosis , Riñón , Macrófagos , Ratas Wistar , Obstrucción Ureteral , Factor A de Crecimiento Endotelial Vascular , Animales , Masculino , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/tratamiento farmacológico , Obstrucción Ureteral/genética , Ratas , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Riñón/efectos de los fármacos , Riñón/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Medicamentos Herbarios Chinos/administración & dosificación , Humanos , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/metabolismo , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/metabolismo , Enfermedades Renales/etiología , Enfermedades Renales/genética , AngiogénesisRESUMEN
CASE SERIES SUMMARY: Four confirmed cases of xanthinuria in cats, and one suspected case based on pedigree analysis, were identified. Clinical presentations varied and included haematuria, pollakiuria, dysuria, and urethral and ureteral obstruction. All cats had upper urinary tract uroliths. Diagnosis was obtained through infrared mass spectrometry of uroliths or urine. Clinical signs commenced at 3-8 months of age and reduced in all cats in the medium to long term after the introduction of a protein-restricted diet. Four cats were castrated males and one was a spayed female. Cases consisted of four Munchkin pedigree cats and one unrelated domestic shorthair cat. All four affected Munchkin pedigree cats were related, with three cases full siblings and the fourth case a half-sibling. No connection to the Munchkin pedigree could be established for the domestic shorthair cat. A candidate causative genetic variant (XDH p.A681V) proposed for this cat was excluded in the Munchkin family. RELEVANCE AND NOVEL INFORMATION: All affected cats presented diagnostic challenges and routine urinalysis was insufficient to obtain a diagnosis. Cases of feline xanthinuria may be underdiagnosed due to situations where uroliths cannot be retrieved for analysis and there is an inability to make a diagnosis using crystal morphology alone on routine urinalysis. Metabolic screening of urine may provide an effective mechanism to confirm xanthinuria in suspected cases where uroliths are inaccessible or absent. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs and urethral obstruction developing secondary to xanthine urolithiasis. A protein-restricted diet appears to reduce clinical signs as part of long-term management. PLAIN LANGUAGE SUMMARY: Four closely related Munchkin cats and one domestic shorthair cat were found with a suspected genetic disease causing high levels of xanthine in their urine. The case series looks at similarities and differences in their clinical signs, as well as difficulties experienced in obtaining a correct diagnosis. All cats had upper urinary tract stones and required metabolic testing of the stones or urine to diagnose. All cats were young when their clinical signs started and were on a high-protein diet. Four cats were desexed males and one was a desexed female. A genetic variant that may have caused the disease in the domestic shorthair cat was ruled out in the Munchkin family. Cases of high xanthine levels in feline urine may be underdiagnosed as the stones may not be accessed for testing. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs. A protein-restricted diet appears to reduce clinical signs as part of long-term management.
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Enfermedades de los Gatos , Linaje , Gatos , Animales , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/orina , Enfermedades de los Gatos/genética , Masculino , Femenino , Urolitiasis/veterinaria , Urolitiasis/diagnóstico , Urolitiasis/orinaRESUMEN
We previously reported that rosmarinic acid (RA) ameliorated renal fibrosis in a unilateral ureteral obstruction (UUO) murine model of chronic kidney disease. This study aimed to determine whether RA attenuates indoxyl sulfate (IS)-induced renal fibrosis by regulating the activation of the NLRP3 inflammasome/IL-1ß/Smad circuit. We discovered the NLRP3 inflammasome was activated in the IS treatment group and downregulated in the RA-treated group in a dose-dependent manner. Additionally, the downstream effectors of the NLRP3 inflammasome, cleaved-caspase-1 and cleaved-IL-1ß showed similar trends in different groups. Moreover, RA administration significantly decreased the ROS levels of reactive oxygen species in IS-treated cells. Our data showed that RA treatment significantly inhibited Smad-2/3 phosphorylation. Notably, the effects of RA on NLRP3 inflammasome/IL-1ß/Smad and fibrosis signaling were reversed by the siRNA-mediated knockdown of NLRP3 or caspase-1 in NRK-52E cells. In vivo, we demonstrated that expression levels of NLRP3, c-caspase-1, c-IL-1ß, collagen I, fibronectin and α-SMA, and TGF- ß 1 were downregulated after treatment of UUO mice with RA or RA + MCC950. Our findings suggested RA and MCC950 synergistically inhibited UUO-induced NLRP3 signaling activation, revealing their renoprotective properties and the potential for combinatory treatment of renal fibrosis and chronic kidney inflammation.
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Cinamatos , Depsidos , Fibrosis , Indicán , Inflamasomas , Riñón , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Ácido Rosmarínico , Transducción de Señal , Animales , Depsidos/farmacología , Depsidos/uso terapéutico , Cinamatos/farmacología , Cinamatos/uso terapéutico , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Transducción de Señal/efectos de los fármacos , Masculino , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Línea Celular , Ratones , Interleucina-1beta/metabolismo , Obstrucción Ureteral/tratamiento farmacológico , Obstrucción Ureteral/patología , Especies Reactivas de Oxígeno/metabolismo , Modelos Animales de Enfermedad , Proteína Smad2/metabolismo , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/metabolismo , Proteína smad3/metabolismo , Caspasa 1/metabolismo , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patologíaRESUMEN
PURPOSE: Urinary biomarkers are known to be able to diagnose renal damage caused by obstruction at an early stage. We evaluated the usefulness of urine N-acetyl-beta-D-glucosaminidase (NAG) to determine the prognosis of antenatal hydronephrosis. MATERIALS AND METHODS: From January 2019 to December 2021, a retrospective study was performed on patients with grade 3 or 4 hydronephrosis. We analyzed the ultrasonographic findings and the urinary NAG/Cr ratio between the laparoscopic pyeloplasty (LP) group and active surveillance (AS) group. RESULTS: A total of 21 children underwent LP for ureteropelvic junction (UPJ) obstruction and 14 children underwent AS. The mean age at the time of examination was 3.7 months (1.7-7.5 months) in the LP and 5.2 months (0.5-21.5 months) in the AS (p=0.564). The mean anteroposterior pelvic diameter was 30.0 mm (15.0-49.0 mm) in the LP and 16.7 mm (9.0-31.3 mm) in the AS (p=0.003). The mean renal parenchymal thickness was 2.6 mm (1.2-3.7 mm) in the LP and 3.8 mm (2.9-5.5 mm) in the AS (p=0.017). The urinary NAG/Cr ratio was 26.1 IU/g (9.8-47.4 IU/g) in the LP and 11.1 IU/g (2.6-18.1 IU/g) in the AS (p=0.003). After LP, the urinary NAG/Cr ratio was significantly reduced to 10.4 IU/g (3.4-14.2 IU/g) (p=0.023). CONCLUSIONS: The urinary NAG/Cr ratio, one of the biomarkers of acute renal injury, is closely related to the degree of hydronephrosis. Therefore, it may be useful to determine whether to perform surgery on the UPJ obstruction and to predict the prognosis.