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.

The predictors of poor outcomes in patients with femoral artery injuries.

PURPOSE: This study investigated the predictors of poor outcomes, including limb loss and death, in patients with femoral artery injuries. PATIENTS AND METHODS: The study included 158 patients aged 2-82 (mean age 28.4 ± 16.5) with femoral arterial injury (common, deep, and superficial femoral artery) that were treated surgically between 2000 and 2010. Isolated venous injuries were excluded. Demographic and clinical data of the patients, including age, gender, admission time, pulse rate and blood pressure, hematocrit value, reason of injury, associated injury, and Mangled Extremity Severity Score (MESS) were recorded. RESULTS: Of the 158 patients, the death and amputation rates were 5.7% (9) and 5.1% (8), respectively. In logistic regression analysis, four variables (pulse rate, MESS, hematocrit, and bone trauma) were found to be independent predictors for poor outcomes. The Odd's ratios and confidence interval values of these variables were as follows: 7.24 (1.94-26.92), 21.75 (5.41-87.48), 5.93 (3.04-11.54) and 7.46 (2.09-9.56), respectively. CONCLUSIONS: The MESS value, presence of bone fracture, hematocrit, and pulse rate on admission are predictive risk factors for poor outcomes in patients with femoral artery injury. Therefore, in these patients, prompt intervention by experienced surgeons is crucial for limb salvage and decreased mortality.

Successful embolectomy in a femoral artery thrombosis caused by femoral artery catheterization in a infant.

In infants, the most common cause of femoral artery is thrombosis and iatrogenic arterial injuries usually occur after femoral artery catheterization procedures. Management of this complication includes heparin infusion, thrombolytic agents, interventional radiologic procedures, surgical thrombectomy and by-pass surgery. Signs of arterial thrombosis developed after femoral artery catheterization procedure in the right lower extremity of 9-month-old female infant with methyl malonic acidemia. Heparin infusion was started after confirming the diagnosis of femoral artery thrombosis by ultrasonography. Because of there was no response to heparin treatment, thrombolytic therapy (t-PA) was started after 24 hours. Again, because of there was no response to all medication, surgical thrombectomy was performed. Was entered right common femoral artery with 3.0 F Fogarty catheter and fresh thrombus material was removed from the proximal and distal segments of the femoral artery. Antegrade and retrograde blood flow was achieved. After the procedure clinical signs and the symptoms of the thrombosis were resolved rapidly. There were no any complications in the postoperative period.This case encouraged us for using surgical thrombectomy in the treatment of femoral artery thrombosis in infants who do not respond to medication.