The Effect of Tadalafil on Renal Fibrosis Induced by Ureteral Obstruction / Efecto del Tadalafil en la Fibrosis Renal Inducida por Obstrucción Uretral

ABSTRACT Objective: It has been reported that phosphodiesterase-5 (PDE-5) inhibitors improve kidney function during acute and chronic renal failure. This study aimed to determine the possible therapeutic effects of tadalafil, a specific PDE-5 inhibitor, on renal fibrosis induced by unilateral ureteral obstruction (UUO). Methods: Male Sprague-Dawley rats were used and randomly divided into three groups (n = 6) as sham-operated, UUO and tadalafil-treated (10 mg/72 hours, ig) UUO (UUO+T) groups. Unilateral ureteral obstruction was induced by complete ligation of the left ureter and 14 days after surgery creatinine clearance, urinary cyclic guanosine monophosphate (cGMP), renal alpha-smooth muscle actin (α-sma) and transforming growth factor βeta (TGF-β) levels, as well as histologic changes, were observed in all the animals. Results: Unilateral ureteral obstruction-induced renal fibrosis was confirmed by increased α-sma level, collagen deposition, tubular dilation, inflammatory cell infiltration and necrosis. An increased renal TGF-β level and decreased urinary cGMP level was also observed in obstructed animals in addition to reduced creatinine clearance. Tadalafil treatment, which restored the animals 'urinary cGMP level, significantly attenuated the fibrotic changes and TGF-β increase in their kidneys. Conclusion: This study suggests that tadalafil treatment ameliorates renal fibrosis by reducing TGF-β expression and may have important clinical relevance since tadalafil is currently used clinically to treat erectile dysfunction and pulmonary hypertension.

RESUMEN Objetivo: Se ha reportado que los inhibidores de la fosfodiesterasa-5 (PDE-5) mejoran las funciones renales durante la insuficiencia renal aguda y crónica. Este estudio tuvo por objetivo determinar los posibles efectos terapéuticos del tadalafil - un inhibidor específico de la PDE-5 - sobre la fibrosis renal inducida por una obstrucción ureteral unilateral (OUU). Métodos: Se utilizaron ratas machos Sprague-Dawley, divididas de manera aleatoria en tres grupos (n = 6): operación simulada, OUU y tratamiento con tadalafil (10 mg/72 horas, IG), y OUU (OUU+T). La obstrucción uretral unilateral fue inducida por una ligadura completa del uréter izquierdo y 14 días después de la cirugía, se observaron niveles de monofosfato de guanosina cíclico (GMP) urinario, alfa-actina de músculo liso (α-SMA), y factor de crecimiento transformante βeta (FCT-β), así como cambios histológicos en todos los animales. Resultados: La fibrosis renal inducida por obstrucción uretral unilateral fue confirmada por un aumento del nivel de α-SMA, deposición de colágeno, dilatación tubular, infiltración de células inflamatorias y necrosis. También se observó un aumento del nivel de FCT-β renal y una disminución del nivel de GMP urinario en los animales con obstrucción, además de una reducción del aclaramiento de la creatinina. El tratamiento con tadalafil, que restauró el nivel de GMP urinario de los animales, atenuó significativamente los cambios fibróticos y el aumento de FCT-β en los riñones. Conclusión: Este estudio sugiere que el tratamiento con tadalafil mejora la fibrosis renal al reducir la expresión de FCT-β y puede tener una importante relevancia clínica por cuanto el tadalafil se usa hoy día clínicamente para tratar la disfunción eréctil y la hipertensión pulmonar.

Simplified method using kidney / ureter / bladder x-ray to determine the appropriate length of ureteral stents

ABSTRACT Purpose: To investigate a method to determine the appropriate length of ureteral stents, given that the stent length may lead to exacerbation of urinary symptoms if the stent crosses the bladder midline. Materials and Methods: We retrospectively reviewed the position of the distal curl of the ureteral stent using kidney/ureter/bladder (KUB) radiographs after ureteroscopic lithotripsy in 165 patients who underwent placement of 24- or 26-cm ureteral stents. According to the KUB findings, we categorized the position of the distal curl of the ureteral stent into two groups. In Group 1, the stents did not cross the midline (appropriate length); in Group 2, the stents crossed the midline (inappropriate length). We assessed several patient parameters (sex, height, body mass index, and stone side) and the index of ureteral length using KUB radiographs ("C-P") and computed tomography (CT, "P-V"). Multivariate analysis was performed to identify the most significant factors affecting the position of ureteral stents. We also calculated the cutoff points of the receiver operating characteristic (ROC) curve of C-P and P-V for the position of ureteral stents. Results: The multivariate analysis showed that C-P was the most significant factor affecting the position of ureteral stents (p < 0.001) in patients with 24- and 26-cm ureteral stents. Comparison of the ROC curves of C-P and P-V showed that C-P was superior to P-V (p < 0.01) in patients with 24- and 26-cm stents. Conclusion: The use of KUB radiographs was effective and simple in determining the appropriate length of ureteral stents.

A large 15 - year database analysis on the influence of age, gender, race, obesity and income on hospitalization rates due to stone disease

ABSTRACT Purpose: To assess the public hospitalization rate due to stone disease in a large developing nation for a 15-year period and its association with socio-demographic data. Materials and Methods: A retrospective database analysis of hospitalization rates in the Brazilian public health system was performed, searching for records with a diagnosis code of renal/ureteral calculi at admission between 1998­2012. Patients managed in an outpatient basis or private care were excluded. Socio-demographic data was attained and a temporal trend analysis was performed. Results: The number of stone-related hospitalizations increased from 15.7%, although the population-adjusted hospitalization rate remained constant in 0.04%. Male:female proportion among hospitalized patients was stable (49.3%:50.7% in 1998; 49.2%:50.8% in 2012), though there was a significant reduction in the prevalence of male hospitalizations (−3.8%;p=0.041). In 2012, 38% of hospitalized patients due to stone disease had 40­59 years-old. The ≥80 years-old strata showed the most significant decrease (−43.44%;p=0.022), followed by the 20­39 (−23.17%;p<0.001) and 0­19 years-old cohorts (−16.73%;p=0.012). Overall, the lowest relative hospitalization rates were found for yellow and indigenous individuals. The number of overweight/obese individuals increased significantly (+20.6%), accompanied by a +43.6% augment in the per capita income. A significant correlation was found only between income and obesity (R=0.64;p=0.017). Conclusions:The prevalence of stone disease requiring hospitalization in Brazil remains stable, with a balanced proportion between males and females. There is trend for decreased hospitalization rates of male, <40 and ≥80 years-old individuals. Obesity and income have a more pronounced correlation with each other than with stone disease.

Preoperative serum albumin as a prognostic factor in patients with upper urinary tract urothelial carcinoma

Purpose The study evaluated whether preoperative measures of the C-reactive protein-based systemic inflammatory response may predict cancer survival independent of tumor stage in patients with upper urinary tract urothelial carcinoma (UTUC). Materials and Methods Between September 1999 and October 2010, 181 patients submitted to radical nephroureterectomy were available for evaluation. Multivariate survival analyses were performed using Cox’s proportional hazards model and the coefficient for each factor was divided by the highest coefficient, multiplied by 4, and rounded to the nearest integer. Results Multivariate analyses showed that tumor location, pathologic T stage, lymphovascular invasion, margin status, and albumin level were independent contributors. The bootstrap-corrected C statistics of the model were 0.813 for disease-specific survival and 0.755 for overall survival, respectively. For time to disease-specific and overall mortality for patients, integrated area under the curve values were 0.792 and 0.739, respectively. When patients were clustered into three groups according to their model-predicted survival, the 5-year disease-specific survival in the low-, intermediate- and high-risk group was 95.4%, 76.2%, and 36.9%, respectively (p<0.001), and were 87.8%, 54.4%, and 31.8%, respectively, for overall survival (p<0.001). Decision curve analysis revealed that the use of model was associated with net benefit gains relative to the treat-all strategy. Conclusions   Pretreatment albumin is a simple biomarker based on routinely available well-standardized measures, and is not an expensive and time-consuming process. Hypoalbuminemia is an independent marker of poor prognosis in patients with upper urinary tract urothelial carcinoma. .

Urine leak in minimally invasive partial nephrectomy: analysis of risk factors and role of intraoperative ureteral catheterization

Purpose To investigate risk factors for urine leak in patients undergoing minimally invasive partial nephrectomy (MIPN) and to determine the role of intraoperative ureteral catheterization in preventing this postoperative complication. Materials and Methods MIPN procedures done from September 1999 to July 2012 at our Center were reviewed from our IRB-approved database. Patient and tumor characteristics, operative techniques and outcomes were analyzed. Patients with evidence of urine leak were identified. Outcomes were compared between patients with preoperative ureteral catheterization (C-group) and those without (NC-group). Univariable and multivariable analyses were performed to identify factors predicting postoperative urine leak. Results A total of 1,019 cases were included (452 robotic partial nephrectomy cases and 567 laparoscopic partial nephrectomy cases). Five hundred twenty eight patients (51.8%) were in the C-group, whereas 491 of them (48.2%) in the NC-group. Urine leak occurred in 31(3%) cases, 4.6% in the C-group and 1.4% in the NC-group (p<0.001). Tumors in NC-group had significantly higher RENAL score, shorter operative and warm ischemic times. On multivariable analysis, tumor proximity to collecting system (OR=9.2; p<0.01), surgeon’s early operative experience (OR=7.8; p<0.01) and preoperative moderate to severe CKD (OR=3.1; p<0.01) significantly increased the odds of the occurrence of a postoperative urine leak. Conclusion Clinically significant urine leak after MIPN in a high volume institution setting is uncommon. This event is more likely to occur in cases of renal masses that are close to the collecting system, in patients with preoperative CKD and when operating surgeon is still in the learning curve for the procedure. Our findings suggest that routine intraoperative ureteral catheterization during MIPN does not reduce the probability of postoperative urine leak. In addition, it adds to the overall ...

Single-session ureteroscopic pneumatic lithotripsy for the management of bilateral ureteric stones

PURPOSE: In nowadays there is no consensus on single-session ureteroscopic lithotripsy (URSL) for the management of bilateral ureteric stones. The aim of this study was to evaluate efficacy and safety of single-session URSL in patients with bilateral ureteric stones. MATERIALS AND METHODS: 41 patients who have undergone bilateral single-session URSL were evaluted in this study. A 8/9.8 Fr Wolf semi-rigid ureteroscope was used for the procedures, and the stones were fragmented with pneumatic lithotripter. RESULTS: A high stone-free rate was achieved (90.2%) after single endoscopic procedure with a retreatment rate of 9.8%. The procedure was most successful for distal ureteric stones with a 96.2% stone-free rate followed by middle ureteric stones with a 81.8% stone-free rate while the least success was achieved for proximal ureteric stones with a 77.7% stone-free rate (p < 0.05). A greater stone-free rate was obtained in those with stones less than 10 mm (93.7%) than in those with stones larger than 10 mm (77.7%) (p < 0.05). Ureteral perforation occurred in only one patient (2.4 %). No long-term complication was observed in any patient. CONCLUSIONS: Bilateral single-session URSL can be performed effectively and safely with a low complication rate in patients with bilateral ureteric stones. It can reduce the need of anaesthetics and hospital stay.

Laparoscopic ureteral reimplant for ureteral stricture

Purpose: Evaluate the initial experience of laparoscopic ureteral reimplant for ureteral stenosis. Materials and methods: From January 2004 to June 2008, 10 patients underwent 11 laparoscopic reconstruction surgeries for ureteral stenosis. Seven cases of stenosis of the distal ureter, two at the level of iliac vessels, a case of bilateral distal stenosis and one in the medium third. Eight ureteroneocystotomies were performed by extravesical technique with anti-reflux mechanism, two cases of vesical reimplant with Boari technique and one case using the psoas hitch technique. Results: The average surgical time was 166 minutes (115-245 min), mean blood loss was 162 mL (100-210 mL) and the average hospital stay was 2.9 days (2-4 days). There were two complications: a lesion of the sigmoid colon identified peroperatively and treated with laparoscopic sutures with good evolution, and a case of ureteral stone obstruction at the 30th day postoperative, treated by laser ureterolitotripsy. All patients had resolution of the stenosis at an average follow-up period of 18 months (3-54 months). Conclusions: Laparoscopic surgery represents a feasible, safe and low morbidity technique for ureteral reimplant in ureteral stenosis.

Simultaneous laparoscopic nephroureterectomy and cystectomy: a preliminary report

PURPOSE: Patients with muscle-invasive bladder cancer and concomitant upper urinary tract tumors may be candidates for simultaneous cystectomy and nephroureterectomy. Other clinical conditions such as dialysis-dependent end-stage renal disease and non-functioning kidney are also indications for simultaneous removal of the bladder and kidney. In the present study, we report our laparoscopic experience with simultaneous laparoscopic radical cystectomy (LRC) and nephroureterectomy. MATERIALS AND METHODS: Between August 2000 and June 2007, 8 patients underwent simultaneous laparoscopic radical nephroureterectomy (LNU) (unilateral-6, bilateral-2) and radical cystectomy at our institution. Demographic data, pathologic features, surgical technique and outcomes were retrospectively analyzed. RESULTS: The laparoscopic approach was technically successful in all 8 cases (7 males and 1 female) without the need for open conversion. Median total operative time, including LNU, LRC, pelvic lymphadenectomy and urinary diversion, was 9 hours (range 8-12). Median estimated blood loss and hospital stay were 755 mL (range 300-2000) and 7.5 days (range 4-90), respectively. There were no intraoperative complications but only 1 major and 2 minor postoperative complications. The overall and cancer specific survival rates were 37.5 percent and 87.5 percent respectively at a median follow-up of 9 months (range 1-45). CONCLUSIONS: Laparoscopic nephroureterectomy with concomitant cystectomy is technically feasible. Greater number of patients with a longer follow-up is required to confirm our results.

Steerable antegrade stenting: a new trick of the trade

INTRODUCTION: Whereas a retrograde attempt to insert an indwelling stent is performed in lithotomy position, usually renal access is gained in a prone position. To overcome the time loss of patient repositioning, a renal puncture can be performed in a modified lithotomy position with torqued truncus and slightly elevated flank. There is a two-fold advantage of this position: transurethral and transrenal access can be obtained using a combined approach. In the present study, this simple technique is used to position a floppy guide wire through a modified needle directly through the renal pelvis into the ureter. MATERIALS AND METHODS: The kidney is punctured in the modified lithotomy position under sonographic control using an initial three-part puncture needle. A floppy tip guide-wire is inserted into the collecting system via the needle after retrieving the stylet. The retracted needle is bent at the tip while the guide-wire is secured in the needle and the collecting system. The use of the floppy tip guide-wire helps to insert the curved needle back into the kidney pelvis, which becomes the precise guidance for the now steerable wire. The desired steerable stent is positioned under radiographic control in a retrograde fashion over the endoscopically harbored tip of the guide-wire. Two patient cohorts (newly described method and conventional method) were compared. RESULTS: The presented steering procedure saves 16.5 mean minutes compared to the conventional antegrade stenting and 79.5 Euros compared to the control group. CONCLUSION: The described combined antegrade-retrograde stent placement through a bent three-part puncture needle results in both clinical superiority (OR time, success rate) and financial benefits.

Ureter retrocava: relato de caso / Retrocaval ureter: a case report

Relata-se o caso de um paciente com ureter retrocava, diagnosticado inicialmente em exame de urografia excretora e confirmado com tomografia computadorizada do abdome. A tomografia computadorizada torna-se necessária não apenas para confirmar a posição do ureter em relação à veiacava inferior, como também para excluir outras doenças que cursam com hidronefrose, pois hidronefrose é o principal achado do ureter retrocava sintomático.

The authors report a case of a patient with retrocaval ureter found out in an excretory urography and confirmed with abdominal computerized tomography. The computerized tomography is necessary to confirm the position of the ureter and to exclude other diseaseswhich are associated with hydronefrosis, the main imaging finding,when there is a symptomatic retrocaval ureter.