Ureteral Dysfunction Research Articles

Preliminary Outcomes of an Innovative Approach to Transvaginal Graft Augmentation for Pelvic Organ Prolapse in the “Post-Mesh Era”

Study Objective The objective of this study is to report the early outcomes of a novel transvaginal reconstructive repair of pelvic organ prolapse (POP) augmented with a “Y-shaped” biologic graft (Axis Dermis). Design Retrospective Cohort Study Setting Urogynecology academic private practice in central Pennsylvania Patients or Participants 36 women who underwent transvaginal pelvic reconstructive surgery with augmentation using Axisтм Dermis graft combined with SSL fixation using polypropylene suture for symptomatic Stage 2 prolapse or higher between April 2019 and October 2019 Interventions All patients underwent transvaginal pelvic reconstructive surgery employing a “Y-shaped” Axisтм Dermis graft reinforced with bilateral permanent (polypropylene) suture suspension to the sacrospinous ligament (SSL). Measurements and Main Results Primary outcome was success of surgery, defined by both subjective and objective results up to 6 months post-operatively. Subjectively, as the resolution of bothersome pelvic prolapse related symptoms as indicated by either negative answers to post-op Pelvic Organ Prolapse Distress Inventory 6 or on follow-up telephone interview. Objectively, as a POP-Q Stage ≤ 1. Secondary outcomes were complications, retreatment, and reoperation. The average patient age and BMI was 69.8 years and 27.9 kg/m2, respectively. The average parity was 2.5. The proportion of women with the pre-op diagnosis of uterovaginal prolapse versus post-hysterectomy vaginal vault prolapse was 72.3% and 27.7%, respectively. The subjective and objective cure rate at 6 months was 97.3% and 94.5%, respectively. There were no major complications. There was one retreatment (with a pessary) at 6 weeks postoperatively. One patient was taken for reoperation for ureteral stent placement after post-op transient ureteral dysfunction. Conclusion In this small cohort, a unique technique for transvaginal pelvic reconstruction using biologic graft augmentation combined with permanent suture (polypropylene) SSL suspension has good short-term cure rates for pelvic organ prolapse, without safety concerns. A larger, longitudinal study is planned to investigate long-term success, cost, and efficacy.

MP46-19 IDENTIFICATION OF A POTENTIAL BIOMARKER FOR STENT-INDUCED URETERAL DYSFUNCTION

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP46)1 Apr 2020MP46-19 IDENTIFICATION OF A POTENTIAL BIOMARKER FOR STENT-INDUCED URETERAL DYSFUNCTION Kymora Scotland*, Zi-ao Huang, Lu Wang, David Chen, Ben Chew, and Dirk Lange Kymora Scotland*Kymora Scotland* More articles by this author , Zi-ao HuangZi-ao Huang More articles by this author , Lu WangLu Wang More articles by this author , David ChenDavid Chen More articles by this author , Ben ChewBen Chew More articles by this author , and Dirk LangeDirk Lange More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000901.019AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ureteral stenting can cause symptoms including pain and discomfort in more than 80% of patients. We propose that this pain may be partly due to dysfunctional ureteral peristalsis. Previous work suggested a role for dilation-induced smooth muscle dysfunction in mediating aperistalsis as well as the Gli family of proteins and erythropoietin in regulating contractility. We sought to further investigate specific mechanisms induced by dilation of the ureter and whether they are alleviated via erythropoietin in a porcine model. METHODS: Pigs were stented for set time periods and evaluated for extent and timing of hydronephrosis, ureteral dilation, and rate of peristalsis. Tissue inflammation was graded by a blinded pathologist. RNA and protein expression analyses were used to identify potential biomarkers for ureteral dysfunction. Ureteral function was assessed via quantification of SM contractile forces. Capillary-electrophoresis mass spectrometry was performed in novel metabolomics experiments to quantify inflammatory markers. RESULTS: Stent placement triggers severe ureteral dilation, moderate hydronephrosis and aperistalsis within 48 hours. Stents resulted in inflammatory changes including increased COX-2 expression, a marker of stretch- induced inflammation. Metabolomics experiments showed PGE2, a COX-2 metabolite, expression to be 50% higher after stenting (p< 0.05). Indwelling stents led to increased Gli1, clusterin alpha (kidney injury marker), and collagen 4A2 (marker of fibrotic change) expression in stented ureters versus controls. Erythropoietin did not improve peristalsis or contraction force but did decrease non-purposeful spasming seen exclusively in stented ureters. CONCLUSIONS: We developed a novel assay for quantifying inflammatory markers following stent placement and identified PGE2 as a biomarker for inflammation-induced ureteral dysfunction. COX-2 expression suggests that stents cause stretch induced inflammation of the ureter. Kidney injury and fibrotic change occur after stent placement, leading to Gli family activation and repair processes. Prophylactic erythropoietin may regulate ureteral stabilization in stretch induced spasming following stent placement. Future work will assess the degree and duration of stent-induced injury on ureteral tissue and function. Source of Funding: DC: Natural Science and Engineering Research Council of Canada, DL: independent investigator grant by Boston Scientific. ZH: Mitacs Accelerate PhD Fellowship sponsored by Lipont Pharmaceuticals. KS: Urology Care Foundation Raju Thomas Research Scholar Award and Boston Scientific © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e681-e681 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kymora Scotland* More articles by this author Zi-ao Huang More articles by this author Lu Wang More articles by this author David Chen More articles by this author Ben Chew More articles by this author Dirk Lange More articles by this author Expand All Advertisement PDF downloadLoading ...

Percutaneous nephrostomy placement in pregnant patients: a retrospective single center experience

Purpose Literature on percutaneous nephrostomy (PCN) placement in pregnant patients is limited. The purpose of this case series of 20 pregnant patients was to report short term maternal and fetal outcomes in this population. Materials and methods A 12-year retrospective study was performed on pregnant patients undergoing PCN. Clinical indications, technical success, maternal outcome, fetal outcome, and complications were obtained from the electronic medical record. Results Indications for PCN placement included urolithiasis (40%), congenital ureteral dysfunction in the setting of prior ureteral repair (30%), obstruction associated pain (15%), infection (10%), and ureteral injury in the setting of surgery for ovarian torsion (5%). Catheter insertion was successful in all patients (n = 20), with one major complication (urosepsis). Follow up data was available in 19 patients (95%). Catheters were in situ for a median of 82 days. All patients had clinical and symptomatic improvement. Emergency C-sections were required in two cases. Radiation exposure data were available in 15 of 19 patients and revealed a median fluoroscopy time of 2.8 min, median cumulative dose of 43 mGy, and median dose area product of 635 µGy × m2. No adverse fetal outcomes were recorded at time of delivery. Conclusion PCN placement has good clinical results as a treatment option for ureteral obstruction in a pregnant cohort.

Abstract No. 575 A retrospective analysis of a single-center experience with percutaneous nephrostomy during pregnancy

Percutaneous nephrostomy has been used to treat symptomatic renal obstruction. Although there have been small published series describing safety and efficacy, this study assesses our experience over 12 years placing PCNs in pregnant women in a tertiary care academic medical center. In this IRB approved study, all patients undergoing percutaneous nephrostomy (PCN) from 7/1/2005 through 7/1/2017 were identified through a Hi-IQ database search. Only patients who were pregnant at the time of PCN placement were included. A retrospective review was performed to include demographics, gestational age, clinical indications, technical success, maternal outcome, fetal outcome, and complications. Twenty-one subjects were included with a median age of 28 (range, 19-38). The median gestational age at the time of intervention was 26 weeks (range, 8-38). Of the 21 patients undergoing percutaneous nephrostomy 7 (33%) had hydronephrosis secondary to calculi, 7 (33%) due to congenital ureteral dysfunction and childhood ureteral re-implantation, 2 (10%) had failed internal ureteral stenting, 2 (10%) had urosepsis. There was one case each of the following: gravid uterus with ureteral compression, ureteral trauma in the setting of surgery for presumed ovarian torsion, and hydronephrosis with associated flank pain. Eleven (52%) patients had moderate hydronephrosis, 8 (38%) had severe hydronephrosis, and 2 (10%) had mild hydronephrosis. Technical success was 100% (21/21). 91.5% of pregnancies continued to term. One fetus in the cohort was delivered prematurely at 31 weeks (4.7% preterm delivery). One pregnancy was terminated as it was undesired. There were no major or minor complications related to the procedure. Percutaneous nephrostomy during pregnancy has excellent technical success and good maternal and fetal outcomes.

Changes in intracellular Ca2+ in the ureter smooth muscle cells of rats with neuropathic urinary tract dysfunction and its significance

Objective To investigate the changes in intracellular Ca2+ in the ureter smooth muscle cells (USMC) of rats with neuropathic urinary tract dysfunction (NUTD) and their significance. Methods Forty-five rats were randomly and averagely divided into NUTD group, experimental control (EC) group and blank control (BC) group.The NUTD group was operated with a spinal cord transection at the first lumbar level and the sacral cord was destroyed; in EC group the spinal process was partly bitten at the same position, but the spinal cord was not transected; BC group was given no operations.One week later, the video-urodynamic was performed to observe the acontractile detrusor (ACD), vesicoureteral reflux (VUR) and urinary tract dysfunction in rats among the NUTD group, EC group and the BC group.Video-urodynamic assessment was performed at the sixth week after operation.Ureter smooth muscle cells (USMC) were obtained by collagenase digestion.Intracellular Ca2+ in the USMC were observed by laser scanning confocal microscope.Then the effects of Bay K8644(10-8 mol/L, 10-7 mol/L, 10-6 mol/L) on cytosolic Ca2+ concentrations( [Ca2+ ]i) in NUTD group were studied by calculating the fluorescence intensity. Results ACD and no detrusor overactivity were found in all rats in NUTD group and without vesicoureteral reflux.Immunofluorescence method confirmed that the cells were USMC.Compared with BC group(31.44±2.82)and EC group(32.06±3.67), the fluorescence intensity(FI) of intracellular Ca2+ in USMC was much lower in the NUTD group(9.80±1.11), and there was significant difference(P<0.05). Bay K8644 (10-8mol/L, 10-7mol/L, 10-6mol/L) increased the FI of [Ca2+ ]I in a concentration-dependent manner, which were 3.80±1.30, 10.04±2.15, 19.89±2.06, respectively, and there was significant difference (P<0.05). Conclusions The decrease in Ca2+ concentration in the ureter smooth muscle cells may be one of the important factors for the primary ureteral dysfunction of NUTD.And calcium channel agonist can be meaningful for adjusting abnormal Ca2+ concentration in USMC of NUTD. Key words: Neurogenic urinary tract dysfunction; Ureter smooth muscle cell; L-type Ca2+ channel; Bay K8644; Laser scanning confocal microscope

Erythropoietin Accelerates the Regeneration of Ureteral Function in a Murine Model of Obstructive Uropathy

Unilateral ureteral obstruction halts ureteral peristalsis, and may cause pain and lead to infection. Ureteral ability to recover after obstruction removal remains unclear. Erythropoietin has protective effects in nonhematopoietic organs and restores peristalsis in hypocontractile intestinal smooth muscle cells. We investigated the role of erythropoietin in ureteral smooth muscle function and its therapeutic value for unilateral ureteral obstruction. Unilateral ureteral obstruction was created for 24, 48 and 72 hours in 22 mice per group using a nontraumatic microclip via laparotomy. We determined erythropoietin, erythropoietin receptor and β-common receptor expression in obstructed and unobstructed ureters by reverse transcriptase-polymerase chain reaction and immunohistochemistry. Ten mice per group received 20 IU erythropoietin for 4 days and controls received saline. Hydronephrosis regression after obstruction removal was assessed by ultrasound. Peristalsis was determined microscopically before and after obstruction removal. Erythropoietin, erythropoietin receptor and β-common receptor were expressed in the unobstructed and obstructed ureters of untreated mice. Erythropoietin mRNA was up-regulated in response to obstruction and erythropoietin expression was identified in ureteral smooth muscle. After obstruction removal hydronephrosis and ureteral dysfunction correlated with obstruction duration. Hydronephrosis resolution and ureteral peristalsis restoration were significantly accelerated in erythropoietin treated mice compared to controls. Erythropoietin treatment significantly promoted functional recovery of the ureter after obstruction removal. Erythropoietin may be a helpful strategy for ureteral motility recovery and hydronephrosis resolution in ureteral obstruction.

Motility of the ureter of the spontaneously hypertensive rat

The spontaneously hypertensive rat (SHR) is a commonly used animal model of hypertension and transplantation studies provide evidence for a renal element to the aetiology of the hypertensive process. This study was designed to test the hypothesis that the contractile function of the ureter of the SHR differs to that of the normotensive control Wistar-Kyoto (WKY) rat. Ureter segments from SHR (n = 16) and WKY (n = 16) were cannulated and pressurised in vitro. Acetylcholine (ACh) was used to stimulate phasic contractile pressure responses. SHR ureter contractile frequencies were significantly greater than those of WKY (6.6 ± 0.8 vs. 3.8 ± 0.2 min(-1) in 10(-5) M ACh; p < 0.01). Magnitudes of contractile responses were not significantly different (SHR 14.3 ± 1.5 mmHg, WKY 15.2 ± 2.1 mmHg). SHR ureteral contractile function differs significantly to that of normotensive WKY. Ureteral dysfunction may be a contributory causative factor in the aetiology of the hypertensive disease process.

Morphology, Calcium Signaling and Mechanical Activity in Human Ureter

We determined the mechanisms of calcium signaling in the human ureter, and the relationship to peristaltic contractions and bundular structure in living tissue, thereby advancing the understanding of ureteral function in health and obstruction and reflux. Confocal imaging of 31 ureters was performed and simultaneous force and calcium measurements were made. Immunohistochemistry and Western blotting were also performed. Confocal imaging showed a 3-dimensional network of smooth muscle bundles with no defined longitudinal or circular layers. Fast propagating Ca waves spread throughout the bundles, were closely associated with contraction and depended on L-type Ca channel entry. Immunohistochemistry and Western blotting demonstrated L-type Ca channels, Ca dependent K channels, sarcoplasmic reticulum Ca-adenosine triphosphatase isoforms 2 and 3, inositol triphosphate, and ryanodine receptors. Modulation of Ca and K channel activity was a potent mechanism for affecting Ca and force, whereas manipulation of the sarcoplasmic reticulum had little effect. To our knowledge this study represents the first measurements of Ca signals in the human ureter obtained during phasic contractions and in response to agonists. Results show that it is controlled by fast propagating Ca waves, which spread rapidly between the muscle bundles, producing regular contractions, and drugs that interfere with excitability or Ca entry through L-type Ca channels have profound effects on Ca signaling and contractility. These data are discussed in relation to the treatment of patients with suspected ureteral dysfunction using Ca entry blockers.

CAVEOLAE ARE NEGATIVE REGULATORS OF TRANSFORMING GROWTH FACTOR-β1 SIGNALING IN URETERAL SMOOTH MUSCLE CELLS

The mechanisms underlying ureteral cell regulation are largely unknown. Previous studies have identified lipid rafts/caveolae as regulators of growth stimulatory signals in ureteral smooth muscle cells (USMCs). In this study we determined whether growth inhibitory signaling by transforming growth factor-beta1 (TGF-beta1) is also regulated by caveolae in USMC. Expression of components of the TGF-beta1 signaling axis in USMCs was determined by immunoblot and mRNA analyses. Growth regulatory activity of TGF-beta1 was assessed by H-thymidine incorporation. In select experiments caveolae were disrupted reversibly by cholesterol depletion and replenishment prior to TGF-beta1 treatment. TGF-beta1-responsive gene expression was evaluated using the TGF-beta1 responsive promoter-reporter construct 3TP-Lux. USMCs expressed TGF-beta1, types I and II TGF-beta1 receptors, and the effector Smad-2. TGF-beta1 potently inhibited DNA synthesis in USMCs (IC50 60 pM). TGF-beta1 mediated DNA synthesis inhibition was potentiated following the disruption of caveolae by cholesterol depletion. This effect was reversible with membrane cholesterol restoration. TGF-beta1 stimulated gene activity was augmented by caveolae disruption, while caveolae reformation returned promoter activity to baseline levels. TGF-beta1 is a potent growth inhibitor of USMCs and its activity can be enhanced by caveolae ablation. These findings suggest a role for TGF-beta1 in the growth regulation of normal ureteral cells and implicate caveolar membrane domains in the negative regulation of TGF-beta1 signaling. These studies may be relevant to ureteral pathologies that are characterized by smooth muscle dysplasia.

CHARACTERIZATION OF URETERAL DYSFUNCTION IN AN EXPERIMENTAL MODEL OF CONGENITAL BLADDER OUTLET OBSTRUCTION

Ureteral dysfunction is a significant sequela of congenital bladder outlet obstruction. However, the structural and functional alterations associated with ureteral dysfunction are not well defined. A model of fetal bladder obstruction in sheep was used to characterize the changes in ureteral smooth muscle, extracellular matrix (ECM) and functional properties in response to bladder outlet obstruction. Partial bladder outlet obstruction was created in fetal sheep at gestational age 95 days via placement of a metal ring around the proximal urethra as well as ligation of the urachus. Ureters were harvested at 109 and 135 days (full term = 140 days) to determine the relative composition of smooth muscle, ECM and urothelium by morphometric analysis and to measure DNA and protein concentrations. Ureteral tissue from 135 day gestation obstructed and control sheep was harvested and immediately placed in Krebs solution. Smooth muscle strips (2-3 mm. x 7-8 mm.) were suspended in organ baths. The frequency and amplitude of spontaneous ureteral contractions was as well as the response to electric field stimulation (EFS) were determined. Bladder outlet obstruction caused a significant increase in ureteral weight, smooth muscle mass and total ECM at both 109 and 135 days gestation. Total ureteral DNA was greater in obstructed compared with sham ureters at 135 days gestation. Obstructed ureters demonstrated greater amplitude and frequency of spontaneous contractions as well as more pronounced response to EFS when compared to sham ureters. The fetal ureter responds to bladder obstruction with smooth muscle hyperplasia and hypertrophy which is associated with increased spontaneous activity and augmented response to EFS. ECM content is markedly increased indicating a shift in the balance of connective tissue synthesis and degradation. Congenital post-obstructive ureteral dysfunction therefore appears to be the result of dysregulated smooth muscle cell growth and altered ECM homeostasis producing abnormal ureteral contractility.

Hypertension following primary bladder closure for vesical exstrophy

Since the initiation of staged reconstruction for bladder exstrophy, hypertension has been a known complication of the procedure. The etiology of the elevation in blood pressure was presumably secondary to ureteral dysfunction caused by edema at the ureterovesical junction and secondary renal obstruction. This report details the clinical course of three patients who developed significant hypertension following primary bladder closure with posterior iliac osteotomies and bony immobilization by skin traction. None of the patients had urinary obstruction and all had their hypertension alleviated by removal of the traction. The presumed etiology of the elevated blood pressure within these patients is similar to that experimentally produce by inappropriately applied traction resulting in tension on the sciatic nerve and reflex induced vasoconstriction. The need to maintain appropriately applied traction and the necessity of monitoring the postoperative blood pressure is stressed.

The Role of Dysfunctional Voiding in Failure or Complication of Ureteral Reimplantation for Primary Reflux

Detrusor and/or urethral sphincter dysfunction is associated with increased failure or complication of ureteral reimplantation. A group of 400 children who underwent ureteral reimplantation was reviewed and the failure rate was determined. Those patients in the primary reflux category who failed were reviewed in detail for voiding dysfunction. Excluding technical error or ureteral dysfunction, the greatest risk for failure or complication of ureteral reimplantation seems to be related to detrusor and/or urethral sphincter dysfunction. Voluntary detrusor-sphincter discoordination seems particularly prevalent in this high risk group. The findings are discussed in relation to the over-all management of these patients.

Hypertension and Plasma Renin Activity in Experimentally Induced Chronic Pyelonephritis

The present authors conducted a series of experiments with mongrel dogs, in which unilateral chronic pyelonephritis was induced and postoperative changes in blood pressure and plasma renin activity were observed over a period of 3 months. The pyelonephritis infection was brought about by a method involving vesicoureteral reflux and ureteral dysfunction, as described in a previous paper. Pre- and postoperative levels of systolic pressure were compared, but no definite trends were found for the first 3 weeks after operation. At 30, 60 and 90 days the pressures were found to have risen by 21.2 +/- 14.6 and 17.1 +/- 16.7 mm Hg, respectively. No appreciable change in the plasma renin activity was found, however, at any stage. From these results it was concluded that experimentally induced chronic pyelonephritis in dogs caused a rise in blood pressure. No connection between the pyelonephritis and the renin angiotensin system was found.

The relation between experimentally induced pyelonephritis and hypertension.

Hypertension resulting from chronic pyelonephritis has been shown in clinical as well as experimental cases, although some authors deny that there is a pathogenic relationship between the two. To throw light on this problem the present authors conducted a series of experiments with mongrel dogs, in which chronic pyelonephritis was induced and postoperative changes in blood pressure and plasma renin activity were observed over a period of 3 months. The pyelonephritis infection was brought about by a method involving vesicoureteral reflux and ureteral dysfunction, as described in a previous paper. Preoperative and postoperative levels of systolic pressure wer compared, but no definit trends were found for the first 3 weeks after operation. At 30, 60 and 90 days the pressures were found to have risen by 21.2 plus or minus 11.2 mmHg, 21.7 plus or minus 14.6 mmHg and 17.1 plus or minus 16.7 mmHg, respectively. Thus there was a significant elevation (p smaller than 0.01). No appreciable change in the plasma renin activity was found, however, at any stage. From these results it was concluded that experimentally induced chronic pyelonephritis in dogs caused a rise in blood pressure. No connection between the pyelonephritis and the renin angiotensin system was found.

Clinical studies on nephrostomy and cutaneous ureterostomy

The present authors made clinical studies on nephrostomy (122 cases including 38 cases of temporary nephrostomy) and cutaneous ureterostomy (33 cases), which had been carried out for the last 10 years (1958 to 1967) in our department, from the standpoints of complication, prognosis and rehabilitation.The results obtained were as follows:1. According to the findings obtained by the histological sections of the kidney at autopsy or of the removed kidney, by renal arteriograms before and after the operation in clinical cases and by microangiograms of canine kidney undergoing nephrostomy, the injury of the kidney due to the insertion of nephrostomy tube was insignificant.2. In both operations, the catheters used as the conduits were an important factor in the pathogenesis of urinary infection occurring after the operation. However, a proper position of nephrostomy tube for good drainage of urine was obtained with relative ease, and in this case the urinary infection was reduced to a minor problem. Whereas, in cutaneous ureterostomy, the disappearance of ureteral peristalsis following the operation, which was demonstrated with electro-ureterography and urometry, could produce the state of poor drainage of urine.3. A disadvantage of nephrostomy was, in a high incidence, to note pyrexia caused by the exchange of nephrostomy tube, While, in cutaneous ureterostomy, the development of the ureteral dysfunction and urinary infection was a serious drawback as a cause bringing about renal failure to a greater extent than that in nephrostomy.4. It was suggested that a preventive measure against the urinary infection was to maintain urinary osmotic pressure below 300 mOsm by the administration of fluids in a sufficient degree and/or an osmotic diuretic, with appropriate chemotherapy.5. In general, urinary diversion for the patients with hydronephrosis resulted in good drainage of urine and the recovery of renal function. However, care must be taken to prevent the poor drainage and urinary infection in the patients with the normal function, because they were readily afflicted with acute pyelonephritis after the operation.6. According to the results obtained by the questionnaire, an inconvenience due to the collecting appliance for urinary fistula was pointed out as a main complaint. Moreover, it has reduced the social activity of the male patients in connection with the occupational and economical problems. Therefore, an improvement on the surgical procedure and collecting device should be first accomplished.7. Comparative studies of both operations in all aspects showed that nephrostomy was a more advisable method than cutaneous ureterostomy.

Pre- and postoperative ureteral dysfunction: Evaluation by radioisotope renograms

Pre- and postoperative ureteral dysfunction: Evaluation by radioisotope renograms

Role of ureter in pathogenesis of ascending pyelonephritis.

It is suggested that the ureter has a dual role in the pathogenesis of most cases of ascending pyelonephritis. Anatomically the ureter provides a direct route of invasion from bladder to kidney because the subepithelial tissues of the bladder, ureter, and renal pelvis are continuous with the interstitial tissue of the kidney. Physiologically the diseased ureter increases the susceptibility of the kidney to infection because ureteral dysfunction generally involves both obstruction and vesicoureteral reflux. The ureter is not an inert tube but an active muscular structure, and recognition of this fact leads to a dynamic, rather than a static, concept of ascending pyelonephritis.