Vesico-ureteric reflux and urinary tract development in the Pax21Neu+/− mouse

2007 ◽  
Vol 293 (5) ◽  
pp. F1736-F1745 ◽  
Author(s):  
Inga J. Murawski ◽  
David B. Myburgh ◽  
Jack Favor ◽  
Indra R. Gupta

Vesico-ureteric reflux (VUR) is a urinary tract abnormality that affects roughly one-third of patients with renal-coloboma syndrome, an autosomal dominant condition caused by a mutation in PAX2. Here, we report that a mouse model with an identical mutation, the Pax2 1Neu+/− mouse, has a 30% incidence of VUR. In VUR, urine flows retrogradely from the bladder to the ureter and is associated with urinary tract infections, hypertension, and renal failure. The propensity to reflux in the Pax2 1Neu+/− mouse is correlated with a shortened intravesical ureter that has lost its oblique angle of entry into the bladder wall compared with wild-type mice. Normally, the kidney and urinary tract develop from the ureteric bud, which grows from a predetermined position on the mesonephric duct. In Pax2 1Neu+/− mice, this position is shifted caudally while surrounding metanephric mesenchyme markers remain unaffected. Mutant offspring from crosses between Pax2 1Neu+/− and Hoxb7/GFP+/− mice have delayed union of the ureter with the bladder and delayed separation of the ureter from the mesonephric duct. These events are not caused by a change in apoptosis within the developing urinary tract. Our results provide the first evidence that VUR may arise from a delay in urinary tract maturation and an explanation for the clinical observation that VUR resolves over time in some affected children.

PEDIATRICS ◽  
1977 ◽  
Vol 59 (4) ◽  
pp. 562-565
Author(s):  
Jacob A. Lohr ◽  
Donna H. Nunley ◽  
Stuart S. Howards ◽  
Raymond F. Ford

Eighteen girls between the ages of 3 and 13 years—with a history of at least three culture-documented episodes of bacteriuria in the previous year, but without radiologic evidence of major urinary tract abnormality—were placed on a double-blind, crossover study comparing the effectiveness of nitrofurantoin macrocrystals against a placebo in preventing the recurrence of bacteriuria. Each child was placed on a daily low dose of nitrofurantoin (1.2 to 2.4 mg/kg/day) or an identical-appearing placebo for six months. Each child was then placed on the opposite capsule for a similar period. There were 35 episodes of bacteriuria (4.2 episodes/patient/yr) in the patients taking the placebo, which compared with a rate of 3.8 episodes/patient/yr during the year prior to the study. Only two episodes (0.2 episodes/patient/yr) occurred in the patients taking the drug. The difference in the rate of recurrent bacteriuria between the girls on placebo and on medication is significant at the 0.01 level using the Wilcoxin matched-pairs test. There were no adverse reactions to the drug. Nitrofurantoin macrocrystals in a single daily low dose appear to be a safe, effective method of preventing recurrent bacteriuria in girls at high risk.


2012 ◽  
Vol 57 (No. 7) ◽  
pp. 380-383 ◽  
Author(s):  
S. Kralova-Kovarikova ◽  
R. Husnik ◽  
D. Honzak ◽  
P. Kohout ◽  
P. Fictum

Stenotrophomonas maltophilia was isolated from three dogs with lower urinary tract disorders. The bacterium was cultured from bladder wall biopsy specimens obtained during cystoscopy, whereas urine culture was negative in all cases. The culture of biopsy specimens is useful and may help with the therapy even if diagnosis of the primary disease has been made.    


2020 ◽  
Vol 185 (11-12) ◽  
pp. e2166-e2170
Author(s):  
Maeghan L Ciampa ◽  
James P Chohonis ◽  
Richard S Otto ◽  
Benjamin T Franklin

Abstract We report on a case of a healthy male patient who was referred to Urology for recurrent persistent urinary tract infections. Investigation revealed a large intraabdominal inflammatory collection abutting the cecum and bladder suspicious for ruptured appendicitis and colovesical fistula. He was taken to the operating room for exploratory laparotomy with General Surgery and Urology and found to have a ruptured appendix secondary to mucinous appendiceal neoplasm with invasion into the cecum and the bladder wall. He then underwent systemic chemotherapy followed by hyperthermic intraperitoneal chemotherapy. He is well with stable right lower quadrant inflammatory collection and without evidence of metastatic disease 22 months following initial surgery. This case presents a rare presentation of a rare disease process that is easy to misdiagnose or be delayed in diagnosis because of its vague and often varied presentation.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Stefan Kohl ◽  
Sandra Habbig ◽  
Lutz T. Weber ◽  
Max C. Liebau

AbstractCongenital anomalies of the kidney and urinary tract (CAKUT) occur in 0.5–1/100 newborns and as a group they represent the most frequent cause for chronic kidney failure in children. CAKUT comprise clinically heterogeneous conditions, ranging from mild vesicoureteral reflux to kidney aplasia. Most forms of CAKUT share the pathophysiology of an impaired developmental interaction of the ureteric bud (UB) and the metanephric mesenchyme (MM). In most cases, CAKUT present as an isolated condition. They also may occur as a component in rare multi-organ syndromes. Many CAKUT probably have a multifactorial etiology. However, up to 20% of human patients and > 200 transgenic mouse models have a monogenic form of CAKUT, which has fueled our efforts to unravel molecular kidney (mal-)development. To date, genetic variants in more than 50 genes have been associated with (isolated) CAKUT in humans. In this short review, we will summarize typical imaging findings in patients with CAKUT and highlight recent mechanistic insight in the molecular pathogenesis of monogenic forms of CAKUT.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Ryan F. Peiffer ◽  
Carly Iulo ◽  
Tessa LeCuyer ◽  
Timothy Bolton

Abstract Background Corynebacterium urealyticum urinary tract infections can result in a rarely reported condition called encrusting cystitis whereby plaque lesions form on and within the urinary bladder mucosa. Chronic lower urinary tract signs manifest subsequent to the infection-induced cystitis and plaque-induced decreased bladder wall distensibility. Because of the organism’s multidrug resistance and plaque forming capability, infection eradication can be difficult. While systemic antimicrobial therapy is the mainstay of treatment, adjunctive surgical debridement of plaques has been used with relative paucity in such cases, thereby limiting our understanding of this modality’s indications and success rate. Consequently, this report describes the successful eradication of Corynebacterium urealyticum encrusting cystitis utilizing a unique timeline of medical and surgical treatments. Additionally, this represents the first reported veterinary case of a vasovagal reaction due to bladder overdistension. Case presentation A 6-year-old female spayed Miniature Schnauzer was evaluated for lower urinary tract clinical signs and diagnosed with Corynebacterium urealyticum encrusting cystitis. The infection was persistent despite prolonged courses of numerous oral antimicrobials and urinary acidification. A unique treatment timeline of intravenous vancomycin, intravesical gentamicin, and mid-course surgical debridement ultimately resulted in infection resolution. During surgery, while the urinary bladder was copiously flushed and distended with saline, the dog experienced an acute vasovagal reaction from which it fully recovered. Conclusions Surgical debridement of bladder wall plaques should be considered a viable adjunctive therapy for Corynebacterium urealyticum encrusting cystitis cases failing to respond to systemic antibiotic therapy. The timing in which surgery was employed in this case, relative to concurrent treatment modalities, may be applicable in future cases of this disease as dictated on a case-by-case basis. If surgery is ultimately pursued, overdistension of the urinary bladder should be avoided, or at least minimized as much as possible, so as to prevent the possibility of a vasovagal reaction.


2004 ◽  
Vol 287 (6) ◽  
pp. F1123-F1130 ◽  
Author(s):  
O. H. Yu ◽  
I. J. Murawski ◽  
D. B. Myburgh ◽  
I. R. Gupta

RET, a tyrosine kinase receptor essential for kidney development, has recently been shown to be important for the formation of the urinary tract. When RET is overexpressed in the HoxB7/Ret transgenic mouse, kidneys are small and cystic, and in some of the mice, the ureters are grossly dilated. Here, we report that the observed ureteral dilatation is associated with the urinary tract abnormality vesicoureteric reflux (VUR), in which urine flows retrogradely from the bladder to the ureter. Reflux was determined in vitro by injecting methylene blue into the bladders of HoxB7/Ret and wild-type mice. At postnatal day 1, 30% of HoxB7/Ret mice had VUR compared with 4% of wild-type mice ( P < 0.05). The length of the intravesical ureteral tunnel was shorter in HoxB7/Ret mice compared with wild-type mice, on both the right and the left sides ( P < 0.05), suggesting a basis for the higher incidence of VUR in these mutants. At embryonic day 11, the ureteric bud was found to exit more caudally from the mesonephric duct in HoxB7/Ret mice, and this may predispose them to VUR ( P < 0.05). Wild-type and HoxB7/Ret mice were tested for reflux at embryonic day 17, and both showed a high frequency of VUR (59 and 75%, respectively). These results suggest that VUR may occur transiently during normal urinary tract development before the ureter has completed its insertion into the bladder. In the HoxB7/Ret mouse, overexpression of RET appears to delay the maturation of the distal ureter, resulting in postnatal VUR. The HoxB7/Ret mouse is thus an important model in which to examine how vesicoureteric reflux arises during urinary tract development.


2020 ◽  
Author(s):  
Jared Honeycutt ◽  
Loc Le ◽  
Yi-Ju Hsieh ◽  
Michael H. Hsieh

AbstractBacterial and parasitic urinary tract infections(UTI) affect many, but our understanding of associated immunity remains poor. Prior work indicates interleukin-22(IL-22) is a key cytokine during infection of other epithelia. We hypothesized IL-22 is crucial during UTI.IL-22-null(KO) and wild-type(wt) mice underwent bladder wall injection with S. haematobium eggs or transurethral infection with uropathogenic E. coli UTI89.IL-22 and its soluble binding protein, IL-22BP, were increased in the bladder after S. haematobium egg injection. Genes typically induced by IL-22(CXCL2, REG3G[antimicrobial defense protein]], S100A8, S100A9, and Areg) were expressed at higher levels following S. haematobium egg injection. IL-22 stimulation of bladder tissue induced REG3B expression. IL-22 receptor alpha-1 expression was detectable in the urothelium by immunofluorescence and qPCR.Injection of S. haematobium eggs into IL-22-KO vs wt mice triggered differential expression of genes related to transferase activity(transferring alkyl or aryl groups) and epithelial cell development. Numerous uroplakin genes were downregulated in egg-injected, IL-22-KO mice versus their wt counterparts. These decreases in uroplakin expression suggest that, as in the gut, IL-22 is important for replenishing the epithelium during infection-related injury.Following transurethral infection with UTI89, IL-22-KO mice had lower bacterial counts in their urine, bladder, and kidneys. Giving stabilized IL-22 cytokine (IL-22-Fc) to UTI89-infected mice led to higher kidney bacterial counts and increased morbidity.Our data suggest that IL-22 is indeed important in urinary tract immunity, and may interfere with clearance of bacteria from the urinary tract, potentially through its role in maintenance of mature urothelium.


Author(s):  
Michael Brückner

Abstract CASE DESCRIPTION A 4-month-old 5.9-kg sexually intact female French Bulldog was presented because of recurrent urinary tract infections in combination with pollakiuria, hematuria, and urinary incontinence. CLINICAL FINDINGS A diagnosis of malakoplakia was made on the basis of results of hematologic and serum biochemical testing, abdominal ultrasonography, bacterial culture, and cystoscopic biopsies of the urinary bladder wall. Biopsy samples were sent for routine histologic examination and fluorescence in situ hybridization to confirm the presence of intracellular and subendothelial bacteria. TREATMENT AND OUTCOME Treatment with enrofloxacin was started after the diagnosis of malakoplakia was confirmed. During treatment, polypoid changes in the urinary bladder decreased dramatically but did not disappear. On follow-up ultrasonography after 12 weeks of treatment, marked improvement was visible and results of repeated bacterial culture and fluorescence in situ hybridization of bladder wall samples were negative. The patient was free from clinical signs and had an ultrasonographically normal urinary bladder 59 weeks after antimicrobial treatment was discontinued. CLINICAL RELEVANCE Malakoplakia, a granulomatous disease characterized by impaired histiocytes that are unable to completely digest phagocytized bacteria, is a very rare disease in dogs, but early suspicion of the condition is essential to allow timely diagnosis and avoid disease progression and the need for prolonged treatment. Malakoplakia should be considered in young dogs with chronic urinary tract infections; the diagnosis can be made through a combination of histologic examination and fluorescence in situ hybridization of bladder wall biopsy samples.


2021 ◽  
Vol 8 (3) ◽  
pp. 01-04
Author(s):  
Sule MB

Urinary calculi are the third most common affliction of the urinary tract only exceeded by urinary tract infections and pathologies of the prostate gland. Urinary tract calculi contribute to a major concern encountered in the practice of urology, it affects about 10-12% of the population with a variable incidence with respect to sex, age, occupation, geographical area, climate, dietary fluid intake, social class and race. Urethral calculus is always found on the site of prostatic urethra, bulbar and fossa navicularis. Primary urethral calculi are usually associated with urethral strictures, posterior urethral valve and a diverticulum. Urethral calculi represent 1-2% of all calculi in the urinary tract. This is a case of a 32-year-old farmer and fisherman who had a retrograde urethrocystography (RUCG) that showed an obstructive prostatic calculus, bladder wall calcification and thickening with contrast refluxing into the seminal vesicles bilaterally.


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