Bladder epithelium is abnormal in patients with neurogenic bladder due to myelomeningocele

Schlager, Theresa A.; Grady, Richard W.; Mills, Stacey E.; Hendley, J. Owen

doi:10.1038/sj.sc.3101565

Cited by 40 publications

(21 citation statements)

References 18 publications

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“…In comparison to PGA augmented bladders, silk scaffolds demonstrated a more robust and continuous urothelial layer. Chronic inflammatory responses, as noted in the PGA implants, are known to attenuate uroplakin expression and disrupt barrier function [45] and therefore their presence may explain the results seen in the present study.…”

Section: Discussionmentioning

confidence: 60%

Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation

Mauney¹,

Cannon²,

Lovett³

et al. 2011

Biomaterials

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Currently, gastrointestinal segments are considered the gold standard for bladder reconstructive procedures. However, significant complications including chronic urinary tract infection, metabolic abnormalities, urinary stone formation, bowel dysfunction, and secondary malignancies are associated with this approach. Biomaterials derived from silk fibroin may represent a superior alternative due their robust mechanical properties, biodegradable features, and processing plasticity. In the present study, we evaluated the efficacy of a gel spun silk-based matrix for bladder augmentation in a murine model. Over the course of 70 d implantation period, H&E and Masson’s trichrome (MTS) analysis revealed that silk matrices were capable of supporting both urothelial and smooth muscle regeneration at the defect site. Prominent uroplakin and contractile protein expression (α-actin, calponin, and SM22α) was evident by immunohistochemical analysis demonstrating maturation of the reconstituted bladder wall compartments. Gel spun silk matrices also elicited a minimal acute inflammatory reaction following 70 d of bladder integration, in contrast to parallel assessments of small intestinal submucosa (SIS) and polyglycolic acid (PGA) matrices which routinely promoted evidence of fibrosis and chronic inflammatory responses. Voided stain on paper analysis revealed that silk augmented animals displayed similar voiding patterns in comparison to non surgical controls by 42 d of implantation. In addition, cystometric evaluations of augmented bladders at 70 d post-op demonstrated that silk scaffolds supported significant increases in bladder capacity, voided volume, and flow rate while maintaining similar degrees of compliance relative to the control group. These results provide evidence for the utility of gel spun silk-based matrices for functional bladder tissue engineering applications.

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Section: Discussionmentioning

confidence: 60%

Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation

Mauney¹,

Cannon²,

Lovett³

et al. 2011

Biomaterials

View full text Add to dashboard Cite

show abstract

“…The presence of pyuria, which is frequently used as a marker of UTI in the general pediatric population [15], lacks the same specificity in the neurogenic bladder population: CICdependent patients often have chronic inflammation of the genitourinary tract as a result of frequent catheterization [16], which confounds the utility of urinary white blood cells in this population. Further, bladder biopsy samples from children with myelomeningocele show abnormal epithelium with evidence of chronic inflammation [17], further limiting the utility of urinary white blood cells in the neurogenic bladder population. Similarly, leukocyte esterase, another component of the urinalysis used clinically to diagnose UTI [18], is directly related to the presence of urinary WBCs, and therefore also has limited utility.…”

Section: Discussionmentioning

confidence: 99%

Predictive ability of NGAL in identifying urinary tract infection in children with neurogenic bladders

Forster

Jackson

et al. 2018

Pediatr Nephrol

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Background Distinguishing between urinary tract infection (UTI) and colonization (UTC) in patients with neurogenic bladders who require clean intermittent catheterization (CIC) is difficult. Urinary neutrophil gelatinase-associated lipocalin concentrations (uNGAL) are increased in UTIs. Our objective was to determine the predictive accuracy of uNGAL for UTI in CIC-dependent children. Methods Cross-sectional study of CIC-dependent patients from August, 2015 to November, 2016. UTI was defined as (1) growth of ≥ 50,000 cfu/mL of a uropathogen, (2) > 10 urinary white blood cells/hpf, and (3) ≥ 2 of the following: temperature > 38 °C, abdominal pain, back pain, worsened incontinence, pain with catheterization, or malodorous/cloudy urine. Positive urine cultures that did not meet these criteria were grouped as UTC, and negative cultures were grouped as no growth. Results Two hundred one patients were included (no growth = 100, UTC = 77, UTI = 24). Median (interquartile range) uNGAL was higher in the UTI group (UTI 1361 (931, 2516) μg/g creatinine, UTC 246 (106, 548) μg/g creatinine, no growth 36 (11, 179) μg/g creatinine, p < 0.01 for all comparisons). The area under the ROC curve for uNGAL for UTI versus no UTI was 0.89, 95% CI (0.80–0.98). Conclusion uNGAL is elevated in CIC-dependent children with UTI compared to those with negative cultures and those with UTC.

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“…A possible explanation for this phenomenon could be in vivo sedimentation of cellular elements in the wall of the neurogenic bladder, especially in cases where the bladder wall is thickened and irregular, forming true sacks or diverticula. According to Schlager et al [26] in 2004, the urothelium of the neurogenic bladder in young patients with myelomeningocele is abnormal, with a loss of uroplakin expression and altered urothelial proliferation. In this patient population, leukocyte excretion levels are not adequate for screening UTI, which should instead be confirmed by a urine culture.…”

Section: Discussionmentioning

confidence: 98%

E. coli virulence factors in children with neurogenic bladder associated with bacteriuria

et al. 2005

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The value of E. coli virulence factors in patients with neurogenic bladder has not been established. The aim of this study is to correlate E. coli virulence factors with asymptomatic and symptomatic UTI in children with neurogenic bladder. Fifty E. coli strains, which were collected in sequence, underwent analysis in relation to: the association to pyuria, serotype (O:H), the presence of genes and expression of fimbriae P, type 1, S and hemagglutinin Dr, the presence of the gene and production of hemolysins and cytotoxins (CNF1). We also analyzed the cell adherence capability and pattern and presence of usp (uropathogenic-specific protein). Pyuria was present in most of the positive urine cultures, with 86% AB and 97% UTI. Low rates of uropathogenic strains were observed in the two groups, with 18% AB and 21% UTI. Type 1 fimbria predominated in 44% of the E. coli strains. Of the bacteria studied, 30% (15 strains) exhibited papG genotypes (11 class II and 4 class III). Of these, 12/15 patients presented AB. Production of hemolysins was detected in 38% of the strains (16 AB and 3 UTI) and usp in only 18% of the strains, with 8 AB and 1 UTI. Adherence tests demonstrated the adhesive capacity in all samples analyzed. Neither group (AB or symptomatic UTI) presented a statistically significant difference in relation to the virulence factors studied. E. coli clones that caused symptomatic UTI in children with neurogenic bladder expressed few virulence factors, with no statistically significant difference in comparison to the AB group.

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Bladder epithelium is abnormal in patients with neurogenic bladder due to myelomeningocele

Cited by 40 publications

References 18 publications

Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation

Evaluation of gel spun silk-based biomaterials in a murine model of bladder augmentation

Predictive ability of NGAL in identifying urinary tract infection in children with neurogenic bladders

E. coli virulence factors in children with neurogenic bladder associated with bacteriuria

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