Mediators of fibrosis and apoptosis in obstructive uropathies

Upper urinary tract obstruction, regardless of its cause, often poses a significant clinical challenge to the urologist. Renal cellular and molecular events that occur in response to upper urinary tract obstruction result in a progressive and permanent loss in renal function when left untreated. These pathologic changes include the development of renal fibrosis, tubular atrophy, interstitial inflammation, and apoptotic renal cell death. Several cytokines and growth factors have been identified as major contributors to obstruction-induced renal fibrosis and apoptotic cell death, most notably transforming growth factor-β1 (TGF-β1), angiotensin, nuclear factor-κB (NF-κB), and tumor necrosis factor-α (TNF-α). This review examines the challenges of upper urinary tract obstruction and the role of these mediators in obstruction-induced renal injury.     

Rosiglitazone Protects Against Cyclosporine-Induced Pancreatic and Renal Injury in Rats

Rosiglitazone (RGTZ) has protective effect against various types of injury. This study was performed to evaluate the effect of RGTZ on pancreatic and renal injury caused by cyclosporine (CsA). CsA (15 mg/kg) and RGTZ (3 mg/kg) were administered alone and together to the rats for 28 days. The effect of RGTZ on CsA-induced pancreatic injury was evaluated by intraperitoneal glucose tolerance test (IPGTT), plasma insulin concentrations and pancreatic beta-cell morphology. The effect of RGTZ on CsA-induced renal injury was evaluated by assessing renal function and pathology; mediators of inflammation and fibrosis such as angiotensin II (AngII), osteopontin (OPN) and transforming growth factor-beta1 (TGF-beta1) and apoptotic cell death. Four weeks of CsA treatment caused diabetes, renal dysfunction, typical pathologic lesions (arteriolopathy, interstitial fibrosis and inflammatory cells infiltration) and apoptotic cell death. RGTZ treatment decreased blood glucose concentration, increased plasma insulin concentration and preserved pancreatic beta islet mass. RGTZ treatment improved renal function and histopathology. Pro-inflammatory and pro-fibrotic molecules such as AngII, OPN and TGF-beta1, and apoptotic cell death also decreased with RGTZ treatment. These data suggest that RGTZ has a protective effect against CsA-induced pancreatic and renal injury.     

Endometriosis of the ureter.

Five patients with ureteric endometriosis are described. Extensive pre-operative investigation failed to reveal the aetiology of the unilateral upper urinary tract obstruction seen in all of these patients. Due to the dense fibrosis that invariably accompanies ureteric endometriosis, early surgical excision of the ureteric stricture permits effective resolution of upper tract dilatation and improved renal salvage.     

经腹腔路径完全腹腔镜下移植肾同侧原肾输尿管全长切除术2例报告（附视频）

目的探讨经腹腔路径完全腹腔镜下移植肾同侧原肾输尿管全长切除术治疗肾移植受者上尿路移行细胞癌的技术要点及临床效果。方法 2例肾移植术后移植肾同侧上尿路移行细胞癌患者,采用经腹腔路径完全腹腔镜下操作方法切除移植肾同侧原肾及输尿管全长。通过腹腔镜切除的原肾及输尿管最终从下腹正中小切口完整取出。结果两例手术时间分别为180,120 min,术中出血量分别为80,20 mL;无术中、术后并发症,术后血红蛋白及血清肌酐无明显变化。术后随访6个月均未出现肿瘤复发及转移。结论经腹腔路径完全腹腔镜下肾输尿管全长切除术治疗肾移植后移植肾同侧上尿路移行细胞癌具有手术损伤小、患者痛苦少、术后恢复快等优点,是一种安全有效的微创治疗方法。     

The outcome of patients on dialysis with upper urinary tract transitional cell carcinoma

PURPOSE: Transitional cell carcinoma is the most common upper urinary tract cancer in Taiwanese patients on dialysis. It is a unique finding compared with Western countries. Unfortunately, the long-term outcomes of patients with upper urinary tract transitional cell carcinoma on dialysis are largely unknown. This study presents clinical outcome of patients on dialysis with upper urinary tract transitional cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the medical records of all patients with upper urinary tract transitional cell carcinoma who had end stage renal disease and underwent dialysis. Traditional prognostic factors including age, sex, tumor grade, stage and tumor location were analyzed with respect to disease recurrence and survival. RESULTS: A total of 73 patients were included in this study. The major complaints were painless gross hematuria and urethral bloody discharge. Disease relapsed in 40 (54.8%) patients at average time of 15 months (2 to 92). Univariate analysis failed to identify significant prognostic factors for recurrence. The average duration between primary and contralateral metachronous upper urinary tract transitional cell carcinoma recurrence was 36 months (range 5 to 96). Patients on dialysis with upper urinary tract transitional cell carcinoma who had previous or concurrent bladder tumor, or who had a history of recurrent bladder tumor, had high contralateral upper urinary tract transitional cell carcinoma recurrence. (p = 0.038) The statistically significant prognostic factor for disease-free survival was pT stage (p = 0.041). CONCLUSIONS: Patients on dialysis with painless gross hematuria or bloody urethral discharge must undergo detail urinary system evaluation. Since patients with upper urinary tract transitional cell carcinoma on dialysis have a high recurrence rate and metachronous or even multiple, early synchronous tumor characteristics that may be missed by imaging, total urinary tract exenteration is a recommended therapeutic option.     

Reconstructive surgery of obstructive disease of the upper urinary tract

Efficacy of reconstructive surgery for the obstructive disease of the upper urinary tract was evaluated. Reconstructive surgery was performed in 75 units of the urinary drainage system of 72 patients between July, 1977 and December, 1987. 44 patients were male and 28 were female. The patients ranged in age 1 to 71, mean +/- S.D. being 43 +/- 14 years old. Original diseases were postoperative scar, scar due to the calculi, injury, retroperitoneal fibrosis, ureteritis, tuberculosis, amyloidosis and multiple ureteral diverticulum. The surgery consisted of ureterocalicostomy, renal descensus, descent of right renal vein, uretero-ureterostomy, ureteroneocystostomy (to the dome of the bladder), psoas bladder hitch and renal autotransplantation. Renal autotransplantation was chosen instead of ileal substitution to preserve the continuity of the urinary drainage system, when the upper urinary tract was extensively damaged. The obstructive change of the upper urinary tract improved or disappeared in 66 of 75 units. However, it persisted in 9 units, which were treated with ureterocalicostomy (wrong technics; in 4 units), ureteroureterostomy (wrong choice of the procedure; in 4 units) and autotransplantation (cessation of anti tbc drugs; in 1 unit). In 3 of these 9 units, additional reconstructive surgery was necessary. One patient who was treated with autotransplantation, died of massive bleeding from rupture of arterial anastomosis on 14th postoperative day. No other life-threatening complications were observed. Deterioration of the renal function was observed in two severely damaged kidneys which were performed autotransplantation, although the obstructive change of their urinary tract completely disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)     

Attenuation of interstitial inflammation and fibrosis by recombinant human erythropoietin in chronic cyclosporine nephropathy

BACKGROUND: Evidence suggests that recombinant human erythropoietin (rHuEPO) protects neurons and cardiomyocytes from acute insults. We investigated the protective effect of rHuEPO on cyclosporine (CsA)-induced renal injury. METHODS: CsA (15 mg/kg/day) was given to rats for 1 or 4 weeks, and rHuEPO was concurrently administered at a dose of 100 units/kg (thrice weekly). Effects of rHuEPO on CsA-induced renal injury were evaluated with tubulointerstitial fibrosis (TIF) score, macrophage infiltration, expression of proinflammatory and profibrotic cytokines, and apoptotic cell death. RESULTS: Administration of rHuEPO decreased TIF score and the number of macrophages, which increased significantly in CsA-treated rat kidneys. At the molecular level, rHuEPO treatment decreased proinflammatory mediators (osteopontin and C-reactive protein) and profibrotic mediators (transforming growth factor-beta1 and transforming growth factor-beta1-inducible gene-h3). Increased apoptotic cell death in CsA-treated rat kidneys was significantly decreased with rHuEPO cotreatment, and apoptosis-related genes were regulated in favor of cell survival (increased Bcl-2 and suppressed caspase-3). CONCLUSION: rHuEPO has a renoprotective effect against chronic CsA-induced renal injury.     

Value of the echography of the maternal kidney during pregnancy

Routine ultrasonographic detection of renal tract dilatations in pregnant women is used to define a high risk population for urinary tract infections. In a first group of 96 patients with symptomatic urinary tract infection, 34% of the cases of uncomplicated infection were accompanied by ultrasonographic abnormalities, while 73% of cases of pyelonephritis presented such signs. Antibody coated bacteria were only found in 12% of uncomplicated urinary tract infections and in 30% of cases of pyelonephritis. In a second group of 273 patients, routine ultrasonography revealed abnormalities in 11.5% of cases. 7.5% of patients had dilatations of the upper renal tract, 2% had renal stones and 2% had occult renal malformations. Dilatations of the upper renal tract were associated with asymptomatic urinary tract infections in 30% of cases. Screening for upper renal tract dilatations is recommended between the 17th and 20th weeks of pregnancy. The presence of such lesions constitutes a risk factor for urinary tract infection and appropriate prophylactic treatment should be prescribed.     

Prognostic variables in patients with transitional cell carcinoma of the renal pelvis and proximal ureter

Recent technological advances in urological endoscopic surgery of the renal pelvis and proximal ureter via ureteroscopy or percutaneous nephroscopy have made it possible to consider parenchymal-sparing procedures in patients with transitional cell carcinoma. To define the role of these procedures in the management of renal pelvic or proximal ureteral transitional cell carcinoma we analyzed retrospectively 31 patients who underwent nephroureterectomy for transitional cell carcinoma of the renal pelvis and/or proximal ureter. High grade upper urinary tract transitional cell carcinoma and a history of metachronous or synchronous bladder transitional cell carcinoma were independent adverse prognostic factors. However, patients with low grade upper urinary tract transitional cell carcinoma and no evidence of a urothelial field change had a 100 per cent 5-year survival rate. It would appear that parenchymal-sparing endoscopic techniques should be regarded with caution in patients with either high grade transitional cell carcinoma of the renal pelvis and proximal ureter or a history of bladder cancer.     

Sonographic assessment of normal renal size in children with myelodysplasia

Periodic assessment of upper urinary tract anatomy and renal size is an important component in the urological management of children with myelodysplasia (spina bifida). As a correlation to a previous study of renal growth in children with spina bifida determined by excretory urography, we evaluated 297 renal ultrasonographic examinations in 145 patients with spina bifida and compared the renal size and growth pattern to those of normal children. Patients with known vesicoureteral reflux (grade 2 or greater), congenital renal anomalies, hydronephrosis, renal scarring or urinary tract surgery were excluded. Mean values and standard deviations for sonographically determined renal length were calculated. In general, mean renal length for each age group was below mean values for normal children. A normal renal growth curve for children with spina bifida, based on sonographic renal measurements, is developed for clinical use.     

肾移植术后并发尿路上皮肿瘤的临床分析

目的 分析肾移植患者并发尿路上皮肿瘤的特点，探讨其诊治方法。方法 自1998～2003年肾移植患者1293例，术后发生尿路上皮恶性肿瘤21例（1．6％）。男4例，女17例。17例原发病为慢性问质性肾炎。发生尿路上皮肿瘤距肾移植6～62个月，平均26个月。其中膀胱癌6例，单侧肾盂或输尿管癌6例，单侧肾盂或输尿管、膀胱癌8例，双侧肾盂输尿管癌1例。10例上尿路肿瘤发生部位与移植肾同侧，4例发生于移植肾对侧。临床症状以无痛性肉服血尿和反复泌尿系感染为主。19例行手术治疗，术后所有患者免疫抑制剂用量减少1／3并辅以局部灌注化疗。结果 2例行姑息性治疗的晚期肿瘤患者分别于发现肿瘤5、8个月死亡。余19例现已随访2～5年。13例肿瘤复发，复发部位为膀胱或对侧原。肾、输尿管。所有患者在免疫抑制剂减量期间均未出现急性排斥。2例因切除移植肾恢复透析，17例肾功能正常。结论 慢性间质性。肾炎导致。肾功能衰竭的。肾移植患者和女性肾移植患者易发生移植后尿路上皮肿瘤；移植肾同侧上尿路较对侧好发肿瘤；对移植肾对侧为首发的上尿路发生肿瘤者可预防性行双侧上尿路根治性切除。     

微通道经皮肾镜取石术治疗上尿路结石的疗效及安全性评价（附4533例报告）

目的：探讨微通道经皮肾镜取石术（mPNI。）治疗上尿路结石的疗效和安全性。方法：1999年9月～2010年12月应用mPNI。治疗上尿路结石患者4533例,其中肾盂及。肾盏结石患者3434例,部分鹿角形肾结石患者324例,完全鹿角形肾结石患者38例,嵌顿性输尿管上段结石患者737例,结石大小12～103mm。采用肋上或肋下入路,经肾乳头穿刺后组肾盏建立手术通道。结果：4528例（99．8％）获得成功,手术时间30～185min,结石清除率分别为：输尿管上段结石99．2％,肾盏或’肾盂结石96．5％,部分鹿角形肾结石92．3％（联合ESWL）,完全鹿角形结石86．2％（联合ESWL）。并发症为输血,占1．39％;术后出血行高选择性肾动脉栓塞占O．13％,胸腔积液占O．13％,结肠损伤占0．11％,液体吸收综合征占O．11％,术后感染性休克占O．06％,无死亡及失肾。结论：采用mPNL治疗包括部分鹿角形肾结石在内的上尿路结石可获得较高的结石取净率,手术安全性高,在减少手术出血、降低输血率和其他并发症方面具有优势。     

TNF-alpha neutralization decreases nuclear factor-kappaB activation and apoptosis during renal obstruction

BACKGROUND: Obstruction of the upper urinary tract is an important cause of progressive renal injury in children. While tumor necrosis factor-alpha (TNF-alpha) and nuclear factor kappaB (NFkappaB) have independently been implicated in the pathophysiology of this process, TNF-alpha's role in obstruction-induced NFkappaB activation has not previously been investigated. MATERIALS AND METHODS: To study this, male Sprague Dawley rats were subjected to 3 days of unilateral ureteral obstruction (UUO) versus sham operation. Twenty-four hours prior to surgery and 2 days after, rats received either a vehicle or a pegylated form of soluble TNF receptor type 1 (PEG-sTNFR1). The kidneys were harvested 3 days postoperatively, and tissue samples were analyzed for TNF-alpha expression (ELISA), NFkappaB activation (EMSA, immunohistochemistry), IkappaB degradation (Western blot), angiotensinogen expression (Western blot), and apoptosis (TUNEL). RESULTS: Renal cortical TNF-alpha levels, NFkappaB activation, IkappaB degradation, angiotensinogen expression, and apoptotic cell death were significantly increased in response to obstruction. In contrast, TNF-alpha neutralization significantly reduced obstruction-induced TNF-alpha production, NFkappaB activation, IkappaB degradation, angiotensinogen expression, and renal tubular cell apoptosis. CONCLUSION: TNF-alpha's potent pro-inflammatory and cytotoxic effect during renal obstruction is directed through NFkappaB activation via increased IkappaB-alpha phosphorylation. As the role of TNF-alpha and NFkappaB in renal obstruction are further defined, the development of therapeutic strategies that limit or prevent obstruction-induced renal injury may be realized.     

Upper urinary tract transitional cell carcinoma in patients with bladder carcinoma and associated vesicoureteral reflux

Of 269 patients with bladder neoplasms treated during a 20-year period 47 had associated vesicoureteral reflux. All 47 patients were followed for 3 years or more, or until death. Upper urinary tract transitional cell cancer developed in 3, each of whom had recurrent bladder cancer. Among the 222 patients who had vesical cancer without reflux transitional cell carcinoma of the ureter developed in only 1, 11 years after transurethral resection for a bladder tumor. The incidences of upper tract transitional cell cancer in patients with and without vesicoureteral reflux were 6.4 and 0.44 per cent, respectively, which support the suggested role of reflux in disseminating or seeding of cancer cells from the bladder into the upper urinary tract. Patients with bladder cancer and associated vesicoureteral reflux have an approximately 15-fold greater risk of upper tract cancer developing compared with those without reflux. We recommend vigilant scrutiny of patients with recurrent bladder cancer and associated vesicoureteral reflux for early detection of upper urinary tract transitional cell carcinoma.     

纤维胆道镜在上尿路结石手术中的应用

目的:探讨纤维胆道镜在上尿路结石手术中的应用价值。方法:为31例复杂上尿路结石(多发肾结石、输尿管多发结石、输尿管结石并肾结石)患者施行手术,5例输尿管切开取石术中结石移位时应用纤维胆道镜协助取石。结果:35例取石成功,1例多发肾结石患者有2颗结石残留于肾盏内,术后2个月体外冲击波碎石术(extracorporeal shock wave lithotripsy,ESWL)治疗后排出,2例输尿管粘膜和1例肾盂粘膜损伤出血。结论:纤维胆道镜用于上尿路结石手术,尤其是复杂性上尿路结石手术,有助于取尽结石,对患者损伤小,是一种安全有效的方法,值得临床推广应用。     

Reflux nephropathy in a patient with crossed renal ectopia with fusion

Crossed renal ectopia with fusion is a rare congenital anomaly of the urinary tract. While vesicoureteral reflux has been noted frequently, reflux nephropathy has rarely been reported with this anomaly. I describe here a case of reflux nephropathy in a patient with crossed renal ectopia with fusion. A 14-year-old boy was referred to our hospital for further examination of proteinuria, detected by the school's annual urinary screening program. Laboratory study revealed proteinuria and renal insufficiency. Abdominal computed tomography and voiding cystography disclosed crossed renal ectopia with fusion and vesicoureteral reflux in each moiety. Renal biopsy of the orthotopic kidney showed diffuse interstitial fibrosis and mononuclear cell infiltration, periglomerular fibrosis, glomerular hypertrophy, and focal and global glomerulosclerosis, which were compatible with reflux nephropathy. A low-protein diet and an administration of angiotensin converting enzyme inhibitor decreased the urinary excretion of protein.     

Management of endourological technics with upper urinary tract diseases except urolithiasis

Fifteen patients with stricture of upper urinary tract and 4 patients suspected of having upper tract carcinoma were managed with endourological (percutaneous or transurethral) techniques. The strictures were treated with various dilation catheters and the optical urethrotome. Eleven cases (73.3%) were successfully treated and satisfactory urinary passage was attained. The 4 patients suspected of having upper tract neoplasms were diagnosed accurately with endoscopy, 2 patients had transitional cell carcinoma of renal pelvis and the others had benign ureteral polyps. The endourological technique was a useful method for the treatment of ureteral stenosis and the diagnosis of upper tract neoplasm except for the treatment of urolithiasis. This technique will become useful tool in urology.     

Assessment of urinary ferritin, CEA and beta 2-MG determinations in patients with urinary tract malignancies

Ferritin, carcinoembryonic antigen (CEA) and beta 2-microglobulin (beta 2-MG) levels in urine from 45 patients with cancer (4 with renal adenocarcinoma, 7 with renal pelvic and ureteral cancer and 34 with bladder cancer) at various stages were clinically evaluated for their significance as parameter of urinary tract malignancies as compared to urinary fibrin/fibrinogen degradation products (FDP) and urine cytology. Ferritin levels for the poorly-differentiated and advanced stage groups were higher than those for the well-differentiated and early stage groups, and were especially high in 5 of the 7 patients with renal pelvic and ureteral cancer and all of the 7 patients with bladder cancer involving the upper urinary tract. These data suggest that determination of urinary ferritin is useful in the detection of urinary tract cancer involving the upper urinary tract. The upper limits of CEA levels were determined respectively according to white blood cell counts in urine. Although, CEA levels were elevated in the poorly-differentiated group and the advanced stage group compared to the well-differentiated and early stage groups, the values were positive in only 12 out of 52 cases (23.1%). These values seemed to be low compared to other reports. beta 2-MG levels increased significantly in the poorly-differentiated and advanced stage groups. However, most cases in the above groups were complicated with pyelonephritis or renal impairment. It is suggested that the urinary beta 2-MG secretion from cancer itself is not so significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modulation of smooth muscle activity by nitric oxide in the human upper urinary tract

The aim of the study was to ascertain whether nitric oxide (NO) might regulate motility in the human upper urinary tract. Smooth muscle activity in the human renal pelvis and proximal ureter was studiedin vitro in organ baths, and nitric oxide synthase (NOS) activity was studied by measurement of citrulline formation. NO, glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) significantly reduced the frequency of spontaneous rhythmic contractions in renal pelvis and proximal ureter. Exogenously applied NO elicited relaxations in pre-contracted renal pelvis. Calciumdependent NOS activity was significant in the renal pelvis but undetectable in the ureter. Also, NOS activity was absent in hydronephrotic renal pelvis. NO, SNP and GTN inhibited smooth muscle activity in the human upper urinary tract. NOS activity was obtained in normal renal pelvis but not in hydronephrotic renal pelvis. Regulation of urinary tract NO concentrations might offer a strategy for treatment of renal colic and disturbances in upper urinary tract motility.