Partial Ureteral Obstruction Research Articles

Urinary Proteome Analysis at 5-Year Followup of Patients With Nonoperated Ureteropelvic Junction Obstruction Suggests Ongoing Kidney Remodeling

Severe ureteropelvic junction obstruction is treated surgically. However, for milder cases most clinical teams adopt a watchful waiting approach and only operate in the presence of significant decline of renal function combined with severe hydronephrosis. Little is known about the long-term consequences of ureteropelvic junction obstruction. Using capillary electrophoresis coupled with mass spectrometry, we analyzed the urinary proteome of 42 patients with ureteropelvic junction obstruction 5 years postoperatively or 5 years following spontaneous resolution. At 5-year followup urinary proteomes were similar between patients with early surgical correction of ureteropelvic junction obstruction and age matched controls. In contrast, urinary proteomes differed significantly between conservatively followed patients and controls. Analyses of the proteomic differences suggested ongoing renal or ureteral remodeling in the conservatively followed patients that was not visible clinically. Long-term followup studies are warranted in patients with ureteropelvic junction obstruction, especially those followed conservatively, to determine whether the observed changes in the urinary proteomes become clinically relevant at a later stage.

Protein kinase C inhibitor prevents renal apoptotic and fibrotic changes in response to partial ureteric obstruction

What's known on the subject? and What does the study add? Protein kinase C inhibitor (PKCI) can decrease glomerular and tubular cell apoptosis and mitosis and attenuate collagen accumulation and fibronectin expression in a PUUO rat model. Although the role of PKC has been well studied in diabetic nephropathy, there is no report on its role in obstructive nephropathy. This investigation evaluated the processes that were associated with the activation of PKCα and PKCβ pathways and showed that PKCI played an important role in the protection of renal function during ureteric obstruction. • To investigate the expression of the protein kinase C (PKC) pathway after partial unilateral ureteric obstruction (PUUO). • To evaluate the therapeutic potential of a PKC inhibitor (PKCI) in obstructive nephropathy. • Thirty-six rats were divided into three groups. One sham-operated group served as the control. The other two groups received PUUO surgery, after which one group received no treatment and the other group was treated with PKCI, chelerythrine. • The severity of hydronephrosis and renal morphology were assessed: tubular and glomerularcell apoptosis, mitosis and interstitial fibrosis were examined using immunohistochemistry. • Western immunoblots were performed to determine fibronectin, transforming growth factor-β (TGF-β), and PKC isoform levels. • Two weeks after PUUO surgery, hydronephrosis progressively developed. Tubular-interstitial fibrosis, collagen deposition and fibronectin expression were increased. • PUUO also activated the expression of PKCα and PKCβ and the translocation of PKCs from cell cytosol to cell membranes. • Treatment with PKCI significantly decreased PKCα and PKCβ expression and translocation in the renal cortex. • Treatment with PKCI also reduced the severity of hydronephrosis, decreased both glomerular and tubular cell apoptosis and mitosis, and attenuated the collagen and fibronectin accumulation in renal interstitium. • Renal tubular apoptosis and interstitial fibrosis after obstructive nephropathy are associated with PKCα and PKCβ activation. • The PKCI, chelerythrine, is capable of decreasing PKC expression and translocation in the renal cortex, suggesting that this inhibitor may have therapeutic potential in the protection of renal function in the first few weeks after PUUO surgery.

Regulation of Aquaporins and Sodium Transporter Proteins in the Solitary Kidney in Response to Partial Ureteral Obstruction in Neonatal Rats

Unilateral ureteral obstruction (UUO) impairs function of the obstructed kidney, and the contralateral nonobstructed kidney compensates depending on the degree and duration of UUO. This study aimed to determine the hemodynamic and molecular changes in the solitary kidney in response to partial ureteral obstruction (PUO) where any compensation from the contralateral kidney was eliminated so that all observed changes in the kidney tissue occurred in the kidney with PUO. Newborn rats were subjected to unilateral left nephrectomy (UNX) within the first 48 h of life and a subset of UNX rats was subjected to severe PUO of the right kidney at day 14. Renal blood flow and whole kidney volume were measured with MRI at week 10. The renal protein abundance of aquaporin 1 (AQP1), AQP2 and AQP3 as well as Na,K-ATPase, NaPi-2 (type 2 sodium-phosphate cotransporter) and NHE3 (type 3 sodium-proton exchanger) were examined by immunoblotting and immunocytochemistry. At 10 weeks of age, the protein abundance of AQP2, AQP3, Na,K-ATPase, NaPi-2 and NHE3 were increased in response to PUO. In contrast, AQP1 expression was markedly decreased compared to sham-operated rats. These findings were confirmed by immunohistochemistry. GFR, urine osmolality and urine sodium excretion were reduced and kidney weight increased in response to PUO. In conclusion, the present study demonstrated major changes in the protein abundance of renal AQP1, AQP2 and AQP3 and sodium transporters in the solitary PUO kidney. These changes were paralleled by decreased urinary sodium excretion and a significant reduction in urinary osmolality from the obstructed kidney, suggesting a functional association between the molecular changes and the ability of the obstructed kidney to handle sodium and water in this solitary kidney model.

Performance of Open Renal and Bladder Surgery at a Freestanding Pediatric Surgery Center

More ambulatory urological surgeries are being performed in children due to innovations in techniques and trends in medical care. Pediatric ambulatory surgery centers are seeing more complex procedures that were traditionally hospital based. A total of 343 open renal and bladder procedures were performed by a single pediatric urologist at a freestanding pediatric surgery center (12 miles from a pediatric hospital) between July 2003 and October 2009. Charts were analyzed to determine the demographics and complications necessitating hospitalization within 48 hours of discharge home. During the study period 28 children (mean age 1.62 years, range 4 months to 6 years) underwent nephrectomy, 50 (2.92 years, 3 months to 12 years) underwent pyeloplasty, 216 (4.01 years, 8 months to 21 years) underwent simple ureteral reimplantation and 49 underwent complex ureteral reimplantation (2.79 years, 5 months to 12 years). Two children were acutely transferred to the hospital, 1 for pain management and 1 for respiratory distress. Two additional children were hospitalized within 48 hours, 1 due to partial ureteral obstruction, and 1 due to dehydration and urinary tract infection. All 4 of these patients underwent simple reimplantation surgery. Carefully selected children undergoing open renal and bladder procedures can be expected to be discharged home on the same day. Older children, those with significant comorbidities and those undergoing procedures later in the day may not be ideal outpatient candidates. Nephrectomy, pyeloplasty and ureteral reimplantation are excellent outpatient procedures for most children.

Renal parenchymal fibrosis and atrophy are not correlated with upper tract dilatation: Long-term study of partial unilateral ureteral obstruction in neonatal mice

Purpose The mechanism underlying the evolution of congenital obstructive hydronephrosis is still unclear. In a previous study, we have shown that it is possible to create renal lesions in newborn mice specific to partial ureteral obstruction. We aimed to study the long-term results of such partial obstruction. Methods Mice were operated on the third day of life. We created 2 groups: partial unilateral obstruction and control. We studied antero-posterior pelvis diameter, kidney length and volume on magnetic resonance imaging at day 10 and 3 months. We assessed ureteric patency by injecting Patent Blue dye. Kidney weight and fibrosis were histologically assessed. Fibrosis was assessed using Sirius Red staining and morphometry. Results Imaging showed parenchymal atrophy in the partially obstructed kidney and compensatory hypertrophy of the contralateral kidney. Pelvis dilatation was detected at day 10 but remained stable without significant increase at 3 months. The patency test confirmed the absence of total obstruction in the long term. There was no correlation between the degree of dilatation and parenchymal atrophy or the contralateral hypertrophy. Pathological studies at 3 months revealed fibrosis in the parenchyma without significant correlation with pelvis dilatation. Conclusions Long-term results confirmed that partial ureteral obstruction in newborn mice produces fibrotic lesions of the renal parenchyma, which are not correlated with dilatation of the upper tract. These results could contribute to the clinical management of obstructive uropathy in children, emphasizing that follow up with simple evaluation of upper tract dilatation is insufficient to predict renal deterioration.

2056 PROPAGATION OF THE ELECTRICAL IMPULSE IN REVERSIBLE UNILATERAL URETERAL OBSTRUCTION AS DETERMINED AT HIGH ELECTROPHYSIOLOGICAL RESOLUTION

You have accessJournal of UrologyStone Disease: Basic Research1 Apr 20112056 PROPAGATION OF THE ELECTRICAL IMPULSE IN REVERSIBLE UNILATERAL URETERAL OBSTRUCTION AS DETERMINED AT HIGH ELECTROPHYSIOLOGICAL RESOLUTION Fayez Hammad, Wim Lammers, Betty Stephen, and Loay Lubbad Fayez HammadFayez Hammad Al Ain, United Arab Emirates More articles by this author , Wim LammersWim Lammers Al Ain, United Arab Emirates More articles by this author , Betty StephenBetty Stephen Al Ain, United Arab Emirates More articles by this author , and Loay LubbadLoay Lubbad Al Ain, United Arab Emirates More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2287AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Several studies have shown that ureteral obstruction results in alterations in ureteral functions including the peristaltic activities and propagation of electrical impulses along the ureter. However, there is no data on the alterations in the ureteral electrical activities following partial or complete reversible ureteral obstruction. Reconstruction of the spatial and temporal pattern of electrical activities by recording simultaneously from a large number of extracellular sites is a relatively new technique that has been used to study the electrical activities in various organs. Therefore, the aim of this study was to investigate the electrical propagation of electrical impulses in a reversible unilateral ureteral (complete or partial) obstruction model in vivo. METHODS In Wistar rats, the left midureter was completely (n=8) or partially (n=7) occluded and released after 24 hours. The electrical activities of the left and right ureter were recorded before, during and after obstruction at different stages up to 2 weeks post-obstruction using a high resolution 64 extracellular electrode probe (16x4 array; inter-electrode distance 0.3mm) which was carefully positioned on the surface of the ureter. RESULTS Complete obstruction caused an immediate increase in frequency of the electrical impulses (from 14.8±1.3 to 18.6±1.7/min, P<0.05) in the left proximal ureter followed by a decrease (1.4±0.9/min; P<0.001) while the velocity gradually decreased (from 1.82±0.12 to 0.79±0.17 cm/sec; P<0.001) within the first 2 days post-reversal. Release of the obstruction gradually restored frequency and velocity, which returned to basal values after 2 weeks. Generally, the alterations in complete and partial obstructions were similar although they were less marked in partial obstruction. Distal to the obstruction site, the impulses either disappeared (38%) or propagated retrogradely (43%) at some stage in the post-obstruction period. These abnormal impulse propagations also gradually disappeared in the post-obstruction stage. CONCLUSIONS Following complete or partial ureteral obstruction, there were immediate and significant changes in the propagation of electrical impulses in the proximal and distal left ureter. These alterations were generally less marked following partial compared to complete obstruction. Reversal of the obstruction resulted in the gradual disappearance of these abnormalities in two weeks. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e823 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Fayez Hammad Al Ain, United Arab Emirates More articles by this author Wim Lammers Al Ain, United Arab Emirates More articles by this author Betty Stephen Al Ain, United Arab Emirates More articles by this author Loay Lubbad Al Ain, United Arab Emirates More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Propagation of the Electrical Impulse in Reversible Unilateral Ureteral Obstruction as Determined at High Electrophysiological Resolution

We investigated the propagation of electrical impulses in a reversible, complete or partial unilateral ureteral obstruction model in vivo. In Wistar rats the left mid ureter was completely (8) or partially (7) occluded and released after 24 hours. We recorded electrical activity of the left and right ureter before, during and after obstruction at different stages up to 2 weeks after obstruction using a high resolution, 64 extracellular electrode probe. Complete obstruction in the left proximal ureter caused an immediate increase in frequency from a mean ± SEM of 14.8 ± 1.3 to 18.6 ± 1.7 per minute (p <0.05), followed by a 1.4 ± 0.9 per minute decrease (p <0.001). Within the first 2 days after reversal velocity gradually decreased from 1.82 ± 0.12 to 0.79 ± 0.17 cm per second (p <0.001). Release of obstruction gradually restored frequency and velocity, which returned to baseline at 2 weeks. Generally the alterations in rats with complete and partial obstruction were similar but they were less marked in those with partial obstruction. Distal to the obstruction site the impulses disappeared (38%) or propagated retrograde (43%) at some stage in the post-obstruction period. These abnormal impulse propagations also gradually disappeared in the post-obstruction stage. After complete or partial ureteral obstruction there were immediate, significant changes in the propagation of electrical impulses in the proximal and distal left ureter, which were generally less marked after partial than after complete obstruction. Reversal of obstruction resulted in the gradual disappearance of this abnormality in 2 weeks.

Causal link between neonatal hydronephrosis and later development of hypertension

1. Although congenital ureteral obstruction is a common disorder in infants, its pathophysiology remains poorly understood and its clinical management continues to be debated. During the past decade, the surgical management of non-symptomatic hydronephrosis in children has become more conservative, but the long-term physiological consequences of this new policy are unclear. 2. In experimental models with complete ureteral obstruction, tubular atrophy and interstitial inflammation occur rapidly. Although this type of obstruction is very rare in clinical practice, it is often referred to in clinical discussions. New studies, using a model with chronic partial ureteral obstruction, have demonstrated that hydronephrosis is associated with renal injuries and is causally related to hypertension. 3. The mechanisms underlying the development of hypertension in experimental hydronephrosis are complex and involve changes in both the renin-angiotensin system and renal sympathetic nerve activity. Furthermore, oxidative stress and nitric oxide deficiency in the diseased kidney, with consequent resetting of the tubuloglomerular feedback mechanism, appear to play a pivotal role in the development and maintenance of hyper-tension. 4. In view of the new knowledge regarding the long-term effects of partial ureteral obstruction, today's non-operative management of hydronephrosis should be reconsidered to prevent obstructive nephropathy and hypertension in later life.

Late-Onset Hemorrhagic Cystitis in Children After Hematopoietic Stem Cell Transplantation (HSCT) for Thalassemia and Sickle Cell Anemia: A Prospective Evaluation of Polyoma (BK) Virus Infection and Treatment with Cidofovir (CDV).

Abstract 1133Poster Board I-155 BackgroundHemorrhagic cystitis (HC) is a significant cause of morbidity after allogeneic HSCT. BK virus infection has been associated with development of HC after HSCT, however most studies detected the virus at the time of cystitis, therefore not allowing estimation of the relationship between BK reactivation and HC. Furthermore little is known about development of late-onset HC in children following HSCT, its association with BK virus and treatment with Cidofovir. Therefore we prospectively investigated BK virus reactivation in pts receiving HSCT from HLA-identical related donors, risk factors for development of HC and treatment efficacy with CDV. Patients and Methods117 pts with thalassemia (n=107) and sickle cell anemia (n=10) with median age of 9 years (range, 1.7-17) were enrolled in this study. All pts received BUCY ± Thiotepa containing conditioning regimens. GVHD prophylaxis was cyclosporine and short MTX ± Thymoglobulin-ATG (in 26 pts). Before August 2006 qualitative BK-PCR was performed on urine samples in pts with HC. Since then we prospectively performed qualitative and quantitative PCR on blood and urine samples collected before conditioning regimen and weekly thereafter until at least 100 days post transplant in 64 pts. The quantitative BK virus assay was performed with Real Time Alert Q-PCR-Nanogen kit. Risk factors for the development of HC were evaluated on univariate and multivariate analysis using cumulative incidence curves and Competing risk regression analysis respectively. The cumulative incidence of HC was estimated considering death without HC as competing event. Nineteen pts with HC were given CDV at 1.5 mg/kg/day 3 times/week (n= 10) or 5 mg/kg/week (n=9). Results60 out of 64 pts (94%) had at least 1 positive and 52 of them (81%) 2 or more positive samples for BK viruria. 34 pts (53%) showed al least 1 and 18 of them (28%) 2 or more positive samples for BK viremia. The number of viral copies varied from <556 to >55 million copies. Median time to platelet engraftment was 23 days (range,8-163) and median number of platelets at onset of HC was 81×109/l (range, 2-274 ×109/l). Thirty pts (26%) developed clinically significant (grade 2 to 4) HC within 1 year after HSCT at a median of 38 days (range, 13- 114). All pts with HC had BK viruria. Coexisting viral infections were found in 3 pts: CMV in 2 and adenovirus in 1. The severity of HC was grade 2 in 24 pts, grade 3 in 2 and grade 4 in 4. The 4 pts with grade 4 HC had moderate or severe hydronephrosis along with partial ureteral obstruction which necessitated ureteral stent placement. The cumulative incidence of grade 2 or 3-4 HC was 21%(95% CI 13%-28%) and 5%(95%CI 2%-10%) respectively. In univariate analysis the use of ATG, peak BK viruria, GVHD and age >8 years were associated with HC. Multivariate analysis confirmed the prognostic importance of ATG (HR=10.5; p=0.001), peak BK viruria >100,000 copies (HR=6.2; p=0.004), and acute GVHD (HR=5.3; p=0.007), but not age for HC development. The cumulative incidence of HC in pts who had 2 adverse factors was 64%, compared with 31% (or 53%) and 10 % who had either one (GVHD or ATG) or none of these factors (p<0.0001). However, there were 10 pts who had at 2 or more time points BK viruria >6 millions copies without developing HC. With a median follow-up among survivors of 35 months (range, 5-61) HC did not have a significant impact on survival.Both dosing schedules of CDV were well tolerated and no cases of dose-limiting nephrotoxicity were observed. The median duration of HC was 17 days (range 9-53). The median duration of therapy was 27 days (range,21-180) with a median of 9 doses given (range,6-22). All pts had clinical response but only 6 pts (32%) had microbiological response at 2 weeks after therapy. None of these patients cleared BK viruria when a complete clinical response was achieved. The median time from clinical response to BK viruria clearance was 74 days (range, 14-176). Ten pts with grade 2 and one with grade 3 HC occurred before prospective trial of CDV had spontaneous resolution of HC. The median duration of HC in these pts was similar to those treated with CDV. ConclusionBK viruria is common after HSCT and high viral load is a risk factor for HC. However, even higher-level BK replication alone is not sufficient to cause HC. Coexisting factors such as the use of ATG and GVHD significantly contribute to the development of HC. Cidofovir may have some activity against BK virus-related HC, although our data showed that spontaneous resolution of HC could also occur. DisclosureNo relevant conflicts of interest to declare DisclosuresOff Label Use: Cidofovir as antiviral drug for treatment of BK virus-related hemorrhagic cystitis.

Effect of partial ureteral obstruction on rat ureteral smooth muscle morphology,autorhythmicity and contractile function

Objective To analyze the effect of paritial unilateral ureteral obstruction(PUUO)on rat ureteral smooth muscle morphology.autorhythmicity and contractile function. Methods Eighty Wistar rats were randomly divided into 4 groups：8-week experimental group(n=20),sham control group 1(n=20).16-week experimental group(n=20)and sham control group 2(n=20).The ex- perimental animalsupper half left ureters(n=40)were embedded into the psoas muscles.Sham con- frol rats only received laparotomy.After the model was established,the rats were sacrificed and car- ried out the experiment strip of the ureter muscle in vitro.The contraction extent and frequency of the muscle strip were determined and the uhrastructural changes were observed by transmission electron microscope. Results The ureteral contractility and contractile frequency in 8-week experimental group were(0.62±0.38)g and(18.52±6.70)／min,and in the sham control group 1 were(O.38±0.36)g and(14.80+4.98)／min.There were significant differences in the 8-week experimental group compared with sham control group(P<0.05).The ureter contractility and contractile frequency of 16-week experimental group were(0.15±0.10)g and(12.84±3.32)／min,while the sham control group were(0.41±0.38)g and(16.48±3.44)／rain.There was a significant decrease in the 16-week experimental group compared with sham control group(P<0.05).In 8-week experimental group there were massive mitochondria in the endochylema of smooth muscle cell,whereas in 16-week expe- rimental group,the number of mitochondria decreased and mitochondria was swelling and vacuolized. There were many collagen fibers in the experimental rats'intercellular substance observed. Conclu- sions The autorhythmicity and contractility of smooth muscle in PUUO rats increased after eight weeks partial blockage,however decreased after sixteen weeks partial blockage.The autorhythmicity and contractility of smooth muscle in 8-week model rats increased maybe due to compensation.Under the transmission elect ron microscope.there were massive mitochondria in the endochylema of smooth muscle eell in 8-week models.while the number of mitochondria decreased and the morphous of mito- chondria was swelling and vacuolized. Key words: Partial ureteral obstruction; Ureter; Smooth muscle; Mitochondrion

Unilateral Hydronephrosis and Partial Ureteral Obstruction by Entrapment in a Granuloma in a Spayed Dog

A 6-year-old, spayed female dog had hydronephrosis and incomplete ureteral occlusion on the left side. An end-to-side ureteral anastomosis was performed. The incomplete ureteral occlusion was determined to be related to an ovarian pedicle granuloma formation and was presumably related to a reaction to the suture material used for ovariohysterectomy (OVH) performed 5 years prior to presentation. Azotemia and hydronephrosis were dramatically improved after surgery, and renal function has been well maintained for 3 years. To the authors' knowledge, a chronic partial ureteral occlusion associated with an ovarian pedicle granuloma from an OVH has not been reported.

Atorvastatin Ameliorates Tubulointerstitial Fibrosis and Protects Renal Function in Chronic Partial Ureteral Obstruction Cases

Tubulointerstitial fibrosis, the histological feature of chronic obstructive nephropathy, is delineated in complete unilateral ureteral obstruction models. Histological changes during chronic partial ureteral obstruction are not well studied. We describe changes in a rat model of partial ureteral obstruction. We examined the effects of atorvastatin on histological alterations, fibrosis and function in this model. All rats underwent right nephrectomy. To create partial ureteral obstruction the left ureter was incorporated into the psoas muscle, which was split and reapproximated. Excretory urogram, histology, Western blot of alpha-smooth muscle actin and renal clearance were examined in rats with sham, 14-day or 30-day partial ureteral obstruction. Obstructed rats received a regular or a diet supplemented with 50 mg/kg body weight atorvastatin per day. At 14 days of partial ureteral obstruction pyelogram showed hydronephrosis, which was more pronounced on obstruction day 30. Histological studies on obstruction days 14 and 30 revealed tubulointerstitial fibrosis in the medulla and cortex. Atorvastatin significantly decreased tubulointerstitial fibrosis seen in alpha-smooth muscle actin expression. On obstruction day 14 or 30 the glomerular filtration rate in rats on a regular diet was significantly lower than in sham PUO rats or rats on atorvastatin. This model of partial ureteral obstruction enables chronic studies of morphological and histological changes of the obstructed kidney. It showed progressive fibrosis and decreased filtration function. Atorvastatin ameliorated fibrosis and helped preserve kidney filtration function.

Age-dependent renal expression of acid-base transporters in neonatal ureter obstruction

Congenital obstructive nephropathy accounts for a major proportion of renal insufficiency in infancy and childhood. In an earlier investigation we demonstrated that bilateral complete ureteral obstruction (BUO) in rats is associated with inadequate urinary acidification [Am J Physiol Renal Physiol. 295(2):F497-506, 2008]. The aim of the study reported here was to determine whether this defect is also associated with unilateral ureteral obstruction (UUO), which is clinically more common than BUO. The time-course of the changes in protein expression levels of major renal acid-base transporters was examined at 7 and 14 weeks in rats with neonatally induced partial unilateral ureteral obstruction (PUUO), which was performed within the first 48 h of life. We observed that protein expression of the renal acid-base transporters NHE3, NBC1, NBCn1, pendrin and Na(+)-K(+)-ATPase was increased in both obstructed and non-obstructed kidneys 7 weeks after the induction of neonatal PUUO. This was confirmed by immunocytochemistry. In contrast, 14 weeks after the induction of PUUO, there was a significant downregulation of the renal acid-base transporters NBC1, NBCn1 and Na(+)-K(+)-ATPase in the obstructed kidneys. These time/age-dependent changes in protein expression were associated with parallel changes in renal function resulting in urine acidification in response to exogenous acid loading. In conclusion, these results show that downregulation of protein expression is a time/age-dependent response to PUUO, which could contribute to the decreased net acid excretion and development of metabolic acidosis in neonatal rats with PUUO.

Does Intervention in Utero Preserve the Obstructed Kidneys of Fetal Lambs? A Histological, Cytological, and Molecular Study

Ureteropelvic junction obstruction is a common cause of end-stage nephropathy in children. Our aim was to investigate whether relief of obstruction in utero can alleviate the development of nephropathy. A silastic tube was tied around the left superior segment ureter to induce unilateral partial ureteral obstruction in 22 fetal sheep at 75- 85 d of gestation. Three weeks later, the tubes were removed to relieve the obstruction in 10 of the 22 lambs. A sham operation was performed on four fetuses (the control). At birth, the lambs were killed, and their kidneys were removed to study the changes in histology, podocytes, and expression of paired-box 2 (PAX2) and VEGF. In the obstructed kidneys, we observed cysts of various sizes in the cortex, fibrosis in the interstitial tissue, much decreased number of glomeruli, severe podocyte foot process fusion, and markedly increased PAX2 and decreased VEGF expressions. However, relief of obstruction preserved the number of glomeruli, significantly increased VEGF expression, reduced fusion of the podocyte foot processes, andrestored expression of PAX2 to some extent. Thus, relief ofobstruction in utero may prevent or attenuate the development ofnephropathy in lambs.

Effect of Tadalafil on Renal Resistivity and Pulsatility Index in Partial Ureteral Obstruction

Introduction: To investigate the effect of tadalafil on Resistivity Index (RI) and Pulsatility Index (PI) in partial unilateral ureteral obstruction (PUUO). Methods: Twelve New Zealand rabbits were assigned into two groups. Baseline renal Doppler ultrasonography (USG) was performed in all rabbits. The rabbits in group 1 received tadalafil for a month (10 mg/72 h) and group 2 was defined as sham. After 1 month, in both groups left PUUO was created. Renal Doppler USG was performed to measure RI and PI parameters of both kidneys on the 4th hour and 1st and 3rd days postoperatively. Results: Baseline renal Doppler USG revealed that there was no difference between two kidneys in both groups. The differences in mean RI and PI values of the kidneys between the sham and tadalafil groups were not statistically significant. Compared with the preoperative values, postoperative RI and PI values for the left kidneys were significantly increased in the period from 4 h to 3 days postoperatively in the sham group (p < 0.05). However, mean RI and PI values were not increased in the tadalafil group when compared with the sham group and this difference between the two groups was significant (p < 0.05). Conclusions: Tadalafil has a lowering affect on RI and PI in experimentally created PUUO.

Comparison of Excretory Urography, Ultrasonography-Guided Percutaneous Antegrade Pyelography, and Renal Doppler Ultrasonography in Rabbits with Unilateral Partial Ureteral Obstruction: An Experimental Study

Summary The aim of this study was to compare diagnostic efficiency of excretory urography (EU), ultrasonography-guided percutaneous antegrade pyelography (UGPAP), and renal Doppler ultrasonography (DUS) in New Zealand rabbits (n= 20) experimentally induced unilateral partial ureteral obstruction. The resistive index (RI) value was obtained from all rabbits prior to the induction. A partial ureteral obstruction was created on the left ureter by laparotomy in all rabbits. Applications of direct renal DUS and renal DUS after furosemide administration were performed on days 1 and 10 post-operation. Rabbits were divided into two groups. Rabbits in the first group were subjected to EU, whereas those in the second group were subjected to UGPAP. The obstructive point was successfully determined all rabbits in the EU group on both days 1 and 10 post-operation, whereas in 8 rabbits on day 1 post-operation and all rabbits on day 10 post-operation in the UGPAP group. On both measurements, the mean RI values of the obstructed and nonobstructed kidneys were different (0.567 vs. 0.494; P<0.001). The RI value of non-obstructed kidneys decreased further with furosemide administration. The mean RI difference (RIΔ) after furosemide administration increased. In conclusion, in addition to EU and UGPAP, commonly used imagining methods in veterinary medicine, renal DUS after diuretic administration should be performed as a non-invasive technique to increase diagnostic efficiency of unilateral partial ureteral obstruction.

Effects of a non‐selective COX inhibitor and selective COX‐2 inhibitors on contractility of human and porcine ureters in vitro and in vivo

Anti-inflammatory drugs are used in the treatment of acute renal colic. The aim of this study was to investigate the effects of selective COX-2 inhibitors and the non-selective COX inhibitor diclofenac on contractility of human and porcine ureters in vitro and in vivo, respectively. COX-1 and COX-2 receptors were identified in human ureter and kidney. Human ureter samples were used alongside an in vivo pig model with or without partial ureteral obstruction. COX-1 and COX-2 receptors were located in human ureters by immunohistochemistry. Diclofenac and valdecoxib significantly decreased the amplitude of electrically-stimulated contractions in human ureters in vitro, the maximal effect (Vmax) being 120 and 14%, respectively. Valdecoxib was more potent in proximal specimens of human ureter (EC50=7.3 x 10(-11) M) than in distal specimens (EC50=7.4 x 10(-10) M), and the Vmax was more marked in distal specimens (22.5%) than in proximal specimens (8.0%) in vitro. In the in vivo pig model, parecoxib, when compared to the effect of its solvent, significantly decreased the maximal amplitude of contractions (Amax) in non-obstructed ureters but not in obstructed ureters. Diclofenac had no effect on spontaneous contractions of porcine ureter in vivo. COX-1 and COX-2 receptors were found to be expressed in proximal and distal human ureter and in tubulus epithelia of the kidney. Selective COX-2 inhibitors decrease the contractility of non-obstructed, but not obstructed, ureters of the pig in vivo, but have a minimal effect on electrically-induced contractions of human ureters in vitro.

Is Robotic Radical Cystectomy an Appropriate Treatment for Bladder Cancer? Short-Term Oncologic and Clinical Follow-Up in 50 Consecutive Patients

Recent case series have now been reported for robotic cystectomy. Despite the novelty of these approaches, few reports have been published on the oncologic and clinical outcomes, even in the short term. We report the oncologic and short-term clinical outcomes of 50 patients who underwent robotic-assisted radical cystectomy. A total of 50 patients underwent robotic-assisted laparoscopic radical cystectomy and extracorporeal urinary diversion for bladder cancer. The outcome measures included the pathologic outcomes, complication rate, timing of adjuvant chemotherapy, disease recurrence, and overall and disease-specific survival. Robotic cystectomy was performed in 40 men and 10 women at a mean age of 63.6 years. Of the 50 patients, 66% had Stage pT2 or less, 14% had pT3 disease, and 20% Stage N+ disease. No patient had positive surgical margins. The mean number of lymph nodes removed was 19 (range 8-37). The mean clinical follow-up was 13.2 months. Seven patients had evidence of recurrent disease. Three patients died of advanced urothelial carcinoma, and two died of other causes. Longer term complications included stomal hernia in 2 and partial ureteral obstruction in 1. Eleven patients underwent adjuvant chemotherapy for Stage pT3 disease and N+ disease at a mean of 7.2 weeks postoperatively. The clinical and oncologic follow-up of patients undergoing robotic radical cystectomy appears to be favorable in the short term. As our follow-up increases, we should expect to continue to truly define the long-term clinical appropriateness and oncologic success of this procedure.

Normal differential renal function does not indicate a normal kidney after partial ureteropelvic obstruction and subsequent relief in 2-week-old piglets

We investigated the functional consequences of relieving ureteric obstruction in young pigs with experimental hydronephrosis (HN) induced by partial unilateral ureteropelvic obstruction. Three groups of animals were followed from the age of 2 weeks to the age of 14 weeks: Eight animals had severe or grades 3-4 HN throughout the study. Six animals had relief of the obstruction after 4 weeks. Six animals received sham operations at both ages. Morphological and functional examinations were performed at age 6 weeks and again at age 14 weeks and consisted of magnetic resonance imaging (MRI), technetium-diethylenetriaminepentaaceticacid ((99m)Tc-DTPA) renography, renal technetium-dimercaptosuccinicacid ((99m)Tc-DMSA) scintigraphy, and glomerular filtration rate (GFR) measurement. After relief of the partial obstruction, there was reduction of the pelvic diameter and improvement of urinary drainage. Global and relative kidney function was not significantly affected by either obstruction or its relief. Renal (99m)Tc-DMSA scintigraphy showed a change in both the appearance of the kidney and a change in the distribution within kidneys even after relief of obstruction. This study shows that partial ureteric obstruction in young pigs may be associated with little effect on global and differential kidney function. However, even after relief of HN, the distribution of (99m)Tc-DMSA in the kidney remains abnormal suggesting that a normal differential renal function may not represent a normal kidney.

Functional Change in Partial or Complete Ureteral Obstruction in Rat Kidney

Functional Change in Partial or Complete Ureteral Obstruction in Rat Kidney