Publications by authors named "Christina B Ching"

52 Publications

Pediatric Urology and International Medical Volunteerism: Where Are We? Where Are We Going?

Urology 2021 Mar 22. Epub 2021 Mar 22.

Division of Urology, The Hospital for Sick Children, Toronto Ontario Canada; Pediatric Urology representatives, Surgical Subcommittee, Section of Global Health, American Academy of Pediatrics. Electronic address:

Objectives: To determine the current landscape of international medical volunteerism (IMV) in pediatric urology.

Methods: A questionnaire regarding IMV participation was distributed to Societies for Pediatric Urology members (SPU), pediatric urology fellows (PUFs), and pediatric urology fellowship program directors (PDs). Questions related to IMV interest, experience, and perceived barriers, as well as the importance of trainee participation.

Results: 98 of 733 SPU members queried responded; 62/98 (63%) having volunteered. There was no difference in gender, age, or years in practice between volunteers and non-volunteers (p>0.05). Non-volunteers were generally interested in participating (26/36; 72%), with lack of time and knowledge of opportunities cited as limitations. 27/46 PUFs and 16/27 PDs submitted responses. 10/27 (37%) of PUFs have participated in IMV. The main perceived barrier to their participation was lack of protected time off. While 2 PUFs (7%) stated IMV was a mandatory component of fellowship, 11/27 (41%) of PUFs vs. 2/16 (13%) of PDs believe IMV should be part of the curriculum (p=0.11). PUFs and PDs similarly ranked importance of trainee IMV participation on Likert scale (median 73 vs. 70, p=0.67). Volunteering SPU respondents ranked trainee participation higher than non-volunteers (median 80 vs. 50, p=0.0004).

Conclusions: While pediatric urology IMV opportunities exist, disseminating this information to interested parties and lack of time are barriers to participation. Amongst SPU members, there is a divide in attitudes regarding the importance of trainee participation. Trainees, however, strongly support IMV participation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2021.02.034DOI Listing
March 2021

Robotic upper tract surgery in infants 6 months or less: is there enough space?

J Robot Surg 2021 Mar 22. Epub 2021 Mar 22.

Department of Urology, Nationwide Children's Hospital, Columbus, OH, USA.

Robot-assisted laparoscopic surgery (RALS) has recently been described in children < 1 year old. However, little data exist on robotic utilization in infants ≤ 6 months old, likely due to concerns for limited intraabdominal space and decreased distance between ports in this cohort. We hypothesized that the robotic approach can be successfully used for infants ≤ 6 months old. A prospectively collected database of patients undergoing urologic robotic surgery at our institution was reviewed. Patients ≤ 6 months and ≥ 4 kg were included. Patient demographics, intraoperative details, hospital length of stay, and complications were reviewed. Descriptive statistics were performed. Twelve patients ≤ 6 months old underwent urologic robotic surgery by three surgeons at our institution (2013-2019): pyeloplasty (6), ureteroureterostomy (4), heminephrectomy (1), and nephrectomy (1). Median age at surgery was 4.75 months (IQR 4, 6). Median weight was 7.09 kg (IQR 6.33, 7.78). Median console time was 105 min (IQR 86, 123). For all procedures, 8-mm robotic arm ports were used. No procedures were converted to open. Median post-operative hospital stay was 24 h (IQR). Febrile UTI was the only complication occurring within 30 days of surgery (n = 4, 33%; 7-20 days, Clavien grade 2). For those undergoing pyeloplasty or ureteroureterostomy (n = 10), postoperative ultrasound showed improved (n = 9) or stable hydronephrosis (n = 1). At a median follow-up of 19.73 months (IQR 4.27, 38.32), no patient required an unplanned secondary intervention. Robotic upper urinary tract surgery is feasible and safe in patients ≤ 6 months of age and can be performed successfully with the same technique as for older children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11701-021-01231-6DOI Listing
March 2021

Does a standardized operative approach in cloacal reconstruction allow for preservation of a patent urethra?

J Pediatr Surg 2021 Jan 14. Epub 2021 Jan 14.

Department of Pediatric Colorectal and Pelvic Reconstructive Surgery, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA. Electronic address:

Background: Cloacal malformations are recognized as a particularly challenging congenital condition to manage and they present with a wide spectrum of anatomical configurations making surgical repair very complicated. Urethral necrosis or urethral loss is a known and devastating complication of cloacal repair. The surgical repair of these malformations has evolved over time and historically only common channel (CC) length was measured. More recently, it has been advocated that the urethral length and the CC are both important in determining surgical repair. The purpose of our study is to evaluate if this surgical approach allows for preservation of a patent urethra.

Methods: A prospective database of all cloaca patients maintained with IRB approval (IRB# STUDY00000721) was retrospectively reviewed. We included any girl with cloacal malformation who underwent primary repair at our institution between May 2014 and December 2019. Standardized preop evaluation with endoscopy and 3-dimentional imaging to assess urethral length and CC length. These measurements were used to determine operative approach. Girls with CC < 1 cm undergo posterior sagittal anorectoplasty and introitoplasty (PSARP + I), those with CC measuring 1-3 cm and urethra > 1.5 cm undergo total urogenital mobilization (TUM) and those with CC > 3 cm or urethra < 1.5 cm undergo urogenital separation (UGS). Postoperative urethral patency was determined at the time of cystoscopy and exam under anesthesia (EUA) 4-6 weeks postoperatively by visualizing a viable and healthy urethra that is catheterizable.

Results: A total of 59 patients met inclusion criteria with a median age of 11.6 months. Four girls underwent PSARP + I, 19 girls had a TUM and 36 girls underwent a UGS. All of the girls who had PSARP +I (n = 4) or TUM (n = 19) had a viable and patent urethra that was catheterizable at the cystoscopy and EUA 4-6 weeks postoperatively. Of the 36 girls who had UGS, all but 2 (5.6%) had a viable and patent urethra that catheterized without problems. Overall, 97% of girls in this cohort had a patent urethra after cloacal repair using this surgical protocol.

Conclusions: The use of a standard protocol that considers urethral and common channel length for cloacal repairs results in a viable and patent urethra in 97% of patients.

Level Of Evidence: Level II.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpedsurg.2021.01.011DOI Listing
January 2021

Acquisition, Divergence, and Personalization of the Female Perineal Microbiomes Are Driven by Developmental Milestones and Disrupted by Urinary Tract Infection: A Pilot Study.

Front Pediatr 2020 8;8:542413. Epub 2020 Dec 8.

Center for Microbial Pathogenesis, Research Institute at Nationwide Children's Hospital, Columbus, OH, United States.

The pediatric perineal microbiomes inhabit a dynamic environment with changes related to diet, toileting habits, and hormonal development. We hypothesized that next-generation sequencing would reveal different perineal bacterial signatures associated with developmental milestones in premenstrual females. Furthermore, we predicted that these microbial changes would be disrupted in premenstrual females with a history of urinary tract infection (UTI). Healthy females were recruited at well-child visits. Subjects were divided into 4 developmental groups: (1) 0-3 month old newborns; (2) 4-10 month old infants transitioning to solid foods; (3) 2-6 year old toddlers peri-toilet training; and (4) 7-12 year old premenstrual girls. A separate group of females with a history of culture proven UTI and off antibiotics >1 month was also recruited. DNA was isolated from swabs of the perineum and subjected to 16S rRNA sequencing. The diversity and species changes between developmental cohorts and age matched children with history of UTI was determined. A total of 75 subjects were recruited: 15 in each group. There was a clear evolution of the perineal microbiomes with development. There was a significant microbial disruption in girls with a history of UTI, irrespective of developmental milestone age group. The periurethral/perivaginal site displayed greater changes in microbiome structure than other sites in girls with a history of UTI. This pilot study evaluates the normal microbiome of the premenstrual girl at specific developmental milestones. Although the number of children per cohort was limited to 15, we observed statistical significance corresponding with developmental milestones. This study provides the first, culture independent delineation of the development of the perineal microbiome in girls. Furthermore, the sites closest to the site of infection appear to be more sensitive to antibiotic remodeling than those more distant. The factors that remodel the perineal microbiomes and predispose females, particularly girls, to UTIs (e.g., increase in uropathogen presence, absence of protective organisms) are unclear. Identification of specific signatures that increase susceptibility to UTI and their sequelae will improve patient care and promote personalized medicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2020.542413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752998PMC
December 2020

Gomco vs. plastibell office circumcision: No difference in overall post-procedural complications and healthcare utilization.

J Pediatr Urol 2021 02 15;17(1):85.e1-85.e7. Epub 2020 Nov 15.

Department of Pediatric Urology, Nationwide Children's Hospital, Columbus OH, USA.

Introduction: Gomco clamp and Plastibell ring are common methods of office circumcision. While they possess similar features, the Plastibell is retained after the procedure which could impact perceived and true outcomes of the procedure.

Objective: This study evaluated differences in complications, interventions, and healthcare utilization between Gomco and Plastibell office circumcision techniques.

Study Design: We retrospectively reviewed urology office performed circumcisions (January 2015-August 2018), limiting analysis to patients with follow-up. Patient demographics and circumcision technique were recorded. Complications, interventions, phone calls, emergency department (ED)/urgent care (UC) visits, and unplanned office visits directly related to the circumcision were recorded. Descriptive statistics for the number of patients experiencing an event and the number of days to event were summarized. Survival analysis with inverse probability of treatment weights was used to estimate hazard and incidence rate ratios (HR and IRR, respectively).

Results: 746 patients were included for analysis. Median time of follow-up was 2.7 weeks (interquartile range 2-5). 257 (34%) patients underwent Gomco circumcision; 489 (66%) underwent Plastibell circumcision. The techniques did not significantly differ for complications (HR = 0.9, p = 0.497), interventions (HR = 0.89, p = 0.498), and hospital visits (HR = 1.0, p = 0.985) (Table), although Plastibell patients presented to the ED/UC more (odds ratio = 1.6, p = 0.02). Plastibell patients generated proportionally more post-procedural phone calls (63 vs. 52%), though not significantly (IRR = 1.11; p = 0.426).

Discussion: Overall, the type of device used for office circumcision, between Gomco clamp and Plastibell ring, does not appear to impact the outcome of circumcision. Providers should perform the method of office circumcision with which they are familiar and comfortable. There is an overall reliance on healthcare resources suggesting poor family preparation of the post-procedural course regardless of the technique, necessitating better patient education. Limitations of this study include its retrospective nature, variability in follow-up between techniques, and variety of providers, limited to pediatric urologists, performing circumcision.

Conclusions: Gomco and Plastibell office circumcision techniques do not significantly differ in post-procedural complications, interventions, unplanned hospital visits, and office phone calls. Plastibell patients do present more often to the ED/UC perhaps as a result of increased anxiety and perceived immediacy of concerns with the device.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2020.11.019DOI Listing
February 2021

Surgical outcomes are equivalent after pure laparoscopic and robotic-assisted pyeloplasty for ureteropelvic junction obstruction.

J Pediatr Urol 2020 Dec 30;16(6):845.e1-845.e6. Epub 2020 Sep 30.

Nationwide Children's Hospital, Division of Urology, 700 Children's Drive, Columbus, OH 43205, USA.

Introduction: Minimally invasive (robotic and pure laparoscopic) pyeloplasty has been increasingly used for treatment of ureteropelvic junction obstruction (UPJO). However, few large-scale studies have compared these two modalities directly.

Methods: We performed a retrospective single-center review of all patients who underwent pure laparoscopic (LP) or robotic pyeloplasty (RALP) between 2007 and 2018. Patients were excluded if the initial surgery at our institution was a redo pyeloplasty or if they lacked follow-up information. Outcomes of interest included operative time, length of stay, and complication rates, including rates of secondary procedures. We compared these outcomes between groups using Student's t test for continuous variables and a Chi-square for categorical variables.

Results: A total of 282 patients were identified. Forty-eight were excluded based on study criteria; therefore, our total study cohort was 234 patients: 119 RALP and 115 LP cases. Overall mean postoperative follow-up time was 20.8 months, with no significant differences between groups. Mean operative time was shorter in the LP group when compared the RALP group (3 h 7 min vs. 3 h 41 min, p < 0.001). There were no significant differences between groups in length of stay (1.22 days vs 1.50 days, p = 0.095). Complications occurred in 52 patients (22.2% of overall cohort) with no difference in incidence between groups. Twenty-five patients (14 in the RALP group and 11 in the LP group) underwent unplanned secondary procedures; 19 of these patients (9 in the RALP group and 10 in the LP group) needed a procedure to address secondary obstruction.

Conclusion: We demonstrated no significant differences between RALP and LP in regards to complication rates. Surgeons performing RALP and LP have the potential to offer the same level of care for the surgical management of UPJO, especially in countries where robotic technology may not be readily available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2020.09.018DOI Listing
December 2020

Anatomic factors predict urinary continence in patient with anorectal malformation.

J Pediatr Urol 2020 Oct 21;16(5):545.e1-545.e7. Epub 2020 Jun 21.

Center for Colorectal and Pelvic Reconstruction, Nationwide Children's Hospital, Columbus, OH, USA.

It has been described that patients with more complex anorectal malformations (ARM), lower sacral ratios and spinal anomalies have poorer rates of fecal and urinary continence. While the ARM subtype has been shown to be an independent predictor of fecal continence, it is not well understood how each of these anatomic factors impact urinary continence. The purpose of this study was to identify anatomic factors associated with urinary continence in children born with ARM. We performed a retrospective review of a large prospectively collected database of children with ARM. Inclusion criteria included diagnosis of ARM, age >4 years, available lateral sacral ratio measurement and presence of spinal MRI. Any child with incomplete or absent continence data was excluded. Continence was defined as voiding per urethra volitionally, dry between voids and ≤1 urinary accident per week. Bivariable tests of association and log-binomial regression models were used to examine association between anatomic factors and urinary continence. A total of 434 patients were included in the study. 57.8% (n = 251) were male. Median age was 8.4 years (IQR 6.0-12.3). With regards to severity of ARM, 20.3% (n = 88) were complex, 23.3% (n = 101) were moderate and 56.5% (n = 245) were simple. Lateral sacral ratio included 11.1% (n = 48) that were <0.4, 36.2% (n = 157) 0.4-0.7 and 52.8% (n = 229) > 0.7. Spine status was found to be myelomeningocele in 4.4% (n = 19), low conus or tethered cord in 34.8% (n = 151) and normal or fatty filum in 60.8% (n = 264). Overall 62.2% were continent. ARM severity, lateral sacral ratio and spine status were each independent predictors of urinary continence on univariate and multivariable analysis. We conclude that in children born with ARM, the severity of ARM, lateral sacral ratio and spine status each independently predict urinary continence. These results allow us to better understand these complex patients and their ability to develop urinary continence. This is crucial in enabling proper patient and family counseling and thus, setting appropriate expectations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2020.06.011DOI Listing
October 2020

Roles for urothelium in normal and aberrant urinary tract development.

Nat Rev Urol 2020 Aug 9;17(8):459-468. Epub 2020 Jul 9.

Nephrology and Urology Research Affinity Group, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

Congenital anomalies of the kidney and urinary tract (CAKUTs) represent the leading cause of chronic kidney disease and end-stage kidney disease in children. Increasing evidence points to critical roles for the urothelium in the developing urinary tract and in the genesis of CAKUTs. The involvement of the urothelium in patterning the urinary tract is supported by evidence that CAKUTs can arise as a result of abnormal urothelial development. Emerging evidence indicates that congenital urinary tract obstruction triggers urothelial remodelling that stabilizes the obstructed kidney and limits renal injury. Finally, the diagnostic potential of radiological findings and urinary biomarkers derived from the urothelium of patients with CAKUTs might aid their contribution to clinical care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41585-020-0348-2DOI Listing
August 2020

Prediction of kidney failure in children with chronic kidney disease and obstructive uropathy.

Pediatr Nephrol 2021 Jan 25;36(1):111-118. Epub 2020 Jun 25.

Center for Surgical Outcomes Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

Background: Obstructive uropathy (OU) is a leading cause of pediatric kidney injury. Accurate prediction of kidney disease progression may improve clinical outcomes. We aimed to examine discrimination and accuracy of a validated kidney failure risk equation (KFRE), previously developed in adults, in children with OU.

Methods: We identified 118 children with OU and an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m in the Chronic Kidney Disease in Children study, a national, longitudinal, observational cohort. Each patient's 5-year risk of kidney failure was estimated using baseline data and published parameters for the 4- and 8-variable KFREs. Discriminative ability of the KFRE was estimated using the C statistic for time-to-event analysis. Sensitivity and specificity were evaluated across varying risk thresholds.

Results: Among the 118 children, 100 (85%) were boys, with median baseline age of 10 years (interquartile range, 6-14). Median eGFR was 42 mL/min/1.73m  (32-53), with a median follow-up duration of 4.5 years (2.7-7.2); 23 patients (19.5%) developed kidney failure within 5 years. The 4-variable KFRE discriminated kidney failure risk with a C statistic of 0.75 (95% CI, 0.68-0.82). A 4-variable risk threshold of ≥ 30% yielded 82.6% sensitivity and 75.0% specificity. Results were similar using the 8-variable KFRE.

Conclusions: In children with OU, the KFRE discriminated the 5-year risk of kidney failure at C statistic values lower than previously published in adults but comparable with suboptimal values reported in the overall CKiD population. The 8-variable equation did not improve model discrimination or accuracy, suggesting the need for continued research into additional, disease-specific markers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04661-wDOI Listing
January 2021

Trans IL-6 signaling does not appear to play a role in renal scarring after urinary tract infection.

J Pediatr Urol 2020 Oct 29;16(5):586-591. Epub 2020 May 29.

Department of Pediatric Urology, Nationwide Children's Hospital, Columbus OH, USA; Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus OH, USA. Electronic address:

Introduction: While inflammation is an important innate defense mechanism against infection, it can also lead to local tissue damage. The trans signaling pathway of interleukin (IL)-6 is a known mediator of inflammation. We hypothesized that the trans IL-6 signaling pathway is associated with the development of post febrile urinary tract infection (UTI) renal scarring.

Objective: To compare soluble regulators of trans IL-6 signaling between patients with a history of febrile UTI who do or do not have renal scarring.

Study Design: After IRB-approval, we collected urine samples in pediatric patients with a history of febrile (≥38 °C) UTI (urine culture >50 K uropathogen) with documented presence or absence of renal scarring on imaging. Samples were collected at a time when patients were not actively infected. Enzyme-linked immunosorbent assays were performed on samples for markers of trans IL-6 signaling: IL-6, soluble (s) IL-6 receptor (R), and soluble (s)gp130, a buffer in trans IL-6 signaling. Values were normalized to urine creatinine. Results were analyzed by t-test or Mann-Whitney U. Spearman rank correlation was used. A p-value of <0.05 was considered significant.

Results: A total of 50 urines from patients with a history of febrile UTI were collected: 23 with and 27 without scarring. There was no difference between groups regarding age or gender. There was no significant difference in urine IL-6, sIL-6R, or sgp130 between those with and without scarring (Figure). While IL-6 values significantly correlated with sIL-6R and sgp130 in those without renal scarring, IL-6 did not correlate with sgp130 in those with scarring. Ratios of IL-6 to sgp130 and sIL-6R to sgp130 were not different between groups.

Discussion: The inflammatory response generated in response to infection is believed to be largely responsible for the development of renal scarring after UTI. IL-6 is a cytokine known to be induced during UTI with a pro-inflammatory pathway, known as trans signaling. This study investigated for differences in markers of trans IL-6 signaling between patients with a history of febrile UTI with and without renal scarring. There was no significant difference between the absolute values or ratio of these markers between groups.

Conclusions: Markers of trans IL-6 signaling are not different between individuals with a history of febrile UTI with and without renal scarring in the non-acute setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2020.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686088PMC
October 2020

Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy.

Pediatr Nephrol 2020 10 22;35(10):1907-1914. Epub 2020 May 22.

Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, OH, 43205, USA.

Background: Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification.

Methods: Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine.

Results: In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR).

Conclusions: In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04602-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502482PMC
October 2020

Impact of successful pediatric ureteropelvic junction obstruction surgery on urinary HIP/PAP and BD-1 levels.

J Pediatr Urol 2020 Oct 29;16(5):592.e1-592.e7. Epub 2020 Mar 29.

Division of Pediatric Urology, Department of Pediatric Surgery, Nationwide Children's Hospital, Columbus, OH, USA; Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. Electronic address:

Introduction: In the pediatric patient whose ureteropelvic junction obstruction (UPJO) is not always symptomatic, imaging is the most common means of detecting surgical success. There is interest, however, in other means of post-operative monitoring. A panel of antimicrobial peptides (AMPs) has been previously found to be elevated in UPJO, but the impact of surgical correction on these AMPs is unknown.

Objective: To determine if elevated levels of candidate urinary AMP biomarkers of urinary tract obstruction decrease following UPJO repair.

Study Design: Pediatric patients undergoing surgical correction of an UPJO were recruited for participation. Bladder urine from uninfected consenting/assenting patients was collected immediately prior to surgery and then at least 6 months afterward. Based on prior studies demonstrating significant elevation of beta defensin 1 (BD-1), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), cathelicidin (LL-37), and neutrophil gelatinase-associated lipocalin (NGAL) in patients with UPJO versus control patients, we performed enzyme-linked immunosorbent assays on these four AMPs to compare their expression before and after surgical intervention. If found to significantly decrease, AMP levels were compared to healthy controls. AMP levels were normalized to urine creatinine. Results were analyzed with paired t test or Wilcoxon test using Graphpad software. Correlation was calculated using Pearson or Spearman correlation. A p-value of <0.05 was considered significant.

Results: 13 UPJO patients were included in this study; 9 were male (69%). Age at surgery was a median of 4.3 years (average 6.1, range 0.4-18.4 years). Follow-up urine samples were collected a median of 27.4 months after surgery (average 27.4; range 7.8-45.3 months). All 13 patients had clinical improvement and/or signs of improved hydronephrosis on post-operative imaging. HIP/PAP and BD-1 significantly decreased in post-surgical samples compared to pre-surgical samples (p = 0.02 and 0.01, respectively); NGAL and LL-37 did not significantly change. Overall, HIP/PAP decreased in 12 patients (92%) and BD-1 decreased in 11 patients (85%). BD-1 levels after successful repair were not different from healthy controls (p = 0.06).

Discussion: Urinary biomarkers of obstruction should detect significant obstructive pathology as well as reflect its resolution. This would enable their use in post-operative monitoring and augment current methods of determining successful surgical outcome through imaging.

Conclusions: The AMPs HIP/PAP and BD-1 are significantly elevated in UPJO but then significantly decrease after pyeloplasty, with BD-1 returning to healthy control levels. As a result, these AMPs could serve as markers of successful surgical intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2020.03.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529730PMC
October 2020

UTIGA: a new society for UTI professionals, researchers and patients.

Nat Rev Urol 2020 Jun;17(6):309-310

Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41585-020-0313-0DOI Listing
June 2020

Albuminuria in Pediatric Neurogenic Bladder: Identifying an Earlier Marker of Renal Disease.

Urology 2019 Nov 24;133:199-203. Epub 2019 Aug 24.

Nephrology and Urology Research Affinity Group, The Research Institute at Nationwide Children's Hospital, Columbus, OH; Nephrology Division, Nationwide Children's Hospital, Columbus, OH; Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH. Electronic address:

Objective: To investigate the role of albuminuria as a clinical marker of early renal disease in children with neurogenic bladder (NGB) in association with commonly used predictors of renal risk.

Methods: Catheterized urine was obtained from 40 patients with NGB at a tertiary pediatric hospital. Albumin-to-creatinine ratio (ACR) was analyzed for associations with estimated glomerular filtration rate, vesicoureteral reflux, hydronephrosis, bladder dynamics, and renal scarring.

Results: About 32% (13/40) of NGB patients had elevated ACR (≥30 mg/g. Elevated ACR was associated with Caucasian race, clean intermittent catheterization, hydronephrosis, and vesicoureteral reflux on univariate analysis. In multivariable analysis, presence of vesicoureteral reflux and use of anticholinergic medication were significant predictors of ACR elevation.

Conclusion: Albuminuria is an established clinical predictor of renal disease and risk for progression to renal failure. The presence of albuminuria in NGB patients with urinary tract abnormalities suggests these patients may be at increased risk for progressive renal disease. This supports the clinical utility of adding ACR to the evaluation of renal risk in pediatric NGB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2019.08.013DOI Listing
November 2019

Krt5 urothelial cells are developmental and tissue repair progenitors in the kidney.

Am J Physiol Renal Physiol 2019 09 19;317(3):F757-F766. Epub 2019 Jul 19.

Nephrology Urology Research Affinity Group, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.

Congenital urinary tract obstruction (UTO) is the leading cause of chronic kidney disease in children; however, current management strategies do not safeguard against progression to end-stage renal disease, highlighting the need for interventions to limit or reverse obstructive nephropathy. Experimental UTO triggers renal urothelial remodeling that culminates in the redistribution of basal keratin 5-positive (Krt5) renal urothelial cells (RUCs) and the generation of uroplakin-positive (Upk) RUCs that synthesize a protective apical urothelial plaque. The cellular source of Upk RUCs is currently unknown, limiting the development of strategies to promote renal urothelial remodeling as a therapeutic approach. In the present study, we traced the origins of adult Upk RUCs during normal development and in response to UTO. Fate mapping analysis demonstrated that adult Upk RUCs derive from embryonic and neonatal Krt5 RUCs, whereas Krt5 RUCs lose this progenitor capacity and become lineage restricted by . However, in response to UTO, -labeled adult Krt5 RUCs break their lineage restriction and robustly differentiate into Upk RUCs. Thus, Krt5 RUCs drive renal urothelial formation during normal ontogeny and after UTO by differentiating into Upk RUCs in a temporally restricted manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.00171.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6766634PMC
September 2019

Analysis of the Ribonuclease A Superfamily of Antimicrobial Peptides in Patients Undergoing Chronic Peritoneal Dialysis.

Sci Rep 2019 05 23;9(1):7753. Epub 2019 May 23.

Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

Infectious peritonitis is a common complication in patients undergoing chronic peritoneal dialysis (PD), limiting the duration of PD as a modality for renal replacement therapy and increasing patient morbidity and mortality. Antimicrobial peptides (AMPs) serve critical roles in mucosal defense, but their expression and activity during peritonitis are poorly understood. We hypothesized that AMPs belonging to the Ribonuclease (RNase) A Superfamily are present in peritoneal fluid and increase during peritonitis in patients undergoing chronic PD. In the absence of peritonitis, we detected RNase 3, RNase 6, and RNase 7 in cell-free supernatants and viable cells obtained from peritoneal fluid of chronic PD patients. The cellular sources of these RNases were eosinophils (RNase 3), macrophages (RNase 6), and mesothelial cells (RNase 7). During peritonitis, RNase 3 increased 55-fold and RNase 7 levels increased 3-fold on average, whereas RNase 6 levels were unchanged. The areas under the receiver-operating characteristic curves for RNase 3 and RNase 7 were 0.99 (95% confidence interval (CI): 0.96-1.0) and 0.79 (95% CI: 0.64-0.93), respectively, indicating their potential as biomarkers of peritonitis. Discrete omental reservoirs of these RNases were evident in patients with end stage kidney disease prior to PD initiation, and omental RNase 3 reactive cells increased in patients undergoing PD with a history of peritonitis. We propose that constitutive and inducible pools of antimicrobial RNases form a network to shield the peritoneal cavity from microbial invasion in patients undergoing chronic PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-44219-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533318PMC
May 2019

Impact on Patient Care of a Multidisciplinary Center Specializing in Colorectal and Pelvic Reconstruction.

Front Surg 2018 19;5:68. Epub 2018 Nov 19.

Center for Colorectal and Pelvic Reconstruction (CCPR), Nationwide Children's Hospital, Columbus, OH, United States.

Many patients with an anorectal malformation (ARM) or pelvic anomaly have associated urologic or gynecologic problems. We hypothesized that our multidisciplinary center, which integrates pediatric colorectal, urologic, gynecologic and GI motility services, could impact a patient's anesthetic exposures and hospital visits. We tabulated during 2015 anesthetic/surgical events, endotracheal intubations, and clinic/hospital visits for all patients having a combined procedure. Eighty two patients underwent 132 combined procedures (Table 1). The median age at intervention was 3 years [0.2-17], and length of follow up was 25 months [7-31]. The number of procedures in patients who underwent combined surgery was lower as compared to if they had been done independently [1(1-5) vs. 3(2-7) ( < 0.001)]. Intubations were also lower [1[1-3] vs. 2[1-6]; < 0.001]. Hospital length of stay was significantly lower for the combined procedures vs. the theoretical individual procedures [8 days [3-20] vs. 10 days [4-16]] < 0.05. Post-operative clinic visits were fewer when combined visits were coordinated as compared to the theoretical individual clinic visits (urology, gynecology, and colorectal) [1[1-4] vs. 2[1-6]; = < 0.001]. Patients with anorectal and pelvic malformations are likely to have many medical or surgical interventions during their lifetime. A multidisciplinary approach can reduce surgical interventions, anesthetic procedures, endotracheal intubations, and hospital/outpatient visits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fsurg.2018.00068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254132PMC
November 2018

Common clinical markers predict end-stage renal disease in children with obstructive uropathy.

Pediatr Nephrol 2019 03 13;34(3):443-448. Epub 2018 Oct 13.

Center for Clinical and Translational Research, Nationwide Children's Hospital, Columbus, OH, 43205, USA.

Background: Obstructive uropathy (OU) is a common cause of end-stage renal disease (ESRD) in children. Children who escape the newborn period with mild-to-moderate chronic kidney disease (CKD) continue to be at increased risk. The predictive ability of clinically available markers throughout childhood is poorly defined.

Methods: Patients with OU were identified in the Chronic Kidney Disease in Children Study. The primary outcome of interest was renal replacement therapy (RRT) (cases). Controls were age matched and defined as patients within the OU cohort who did not require RRT during study follow-up.

Results: In total, 27 cases and 41 age-matched controls were identified. Median age at baseline and age at outcome measurement were 10 vs. 16 years, respectively. First available glomerular filtration rate (GFR) (36.9 vs. 53.5 mL/min per 1.73 m), urine protein/creatinine (Cr) (0.40 vs. 0.22 mg/mg) and microalbumin/Cr (0.58 vs. 0.03 mg/mg), and serum CO (20 vs. 22 mmol/L) and hemoglobin (12.4 vs. 13.2 g/dL) differed significantly between cases and controls, respectively. GFR declined 3.07 mL/min per 1.73 m/year faster in cases compared to that in controls (p < 0.0001). Urine protein/Cr and microalbumin/Cr increased by 0.16 and 0.11 per year more in cases compared to those in controls, respectively (p ≤ 0.001 for both). Serum phosphate increased by 0.11 mg/dL and serum albumin and hemoglobin decreased by 0.04 (g/dL) and 0.14 (g/dL) per year more for cases compared to those for controls, respectively (p < 0.05 for all).

Conclusions: Age-specific baseline and longitudinal measures of readily available clinical measures predict progression to ESRD in children with mild-to-moderate CKD from OU.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-018-4107-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500428PMC
March 2019

Novel role for androgen signaling in pyelonephritis.

Kidney Int 2018 09;94(3):455-457

Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; Division of Nephrology, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA. Electronic address:

Sex differences in urinary tract infection (UTI) susceptibility and severity are known, but have historically focused on anatomic differences between males and females. Until recently, experimental UTI has been limited to female animals due to ease of transurethral bladder catheterization. Olson and colleagues have developed a model of experimental UTI independent of sex that relies on direct bladder inoculation and thus permits investigation of sex differences in UTI susceptibility. They now build upon their prior work in this model by implicating androgens as drivers of tubular invasion by uropathogenic Escherichia coli, which form luminal bacterial communities preceding renal abscess formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2018.05.020DOI Listing
September 2018

Combination treatment for cicatrix after neonatal circumcision: An office-based solution to a challenging problem.

J Pediatr Urol 2018 10 28;14(5):471-475. Epub 2018 Jun 28.

Section of Urology, Nationwide Children's Hospital, Columbus, OH, USA; Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Cicatrix formation, which can form after neonatal circumcision to entrap the glans penis, presents a therapeutic challenge. Previous studies in the literature have described either using a topical steroid cream or stretching of the scar tissue with an instrument but not a combination of both modalities. In our experience, monotherapy has resulted in significant recurrence and/or need for further treatment. We present our successful experience that combines cicatrix stretching with a hemostat using local anesthesia in the office followed by several weeks of topical steroids with a minority of patients needing any additional therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2018.05.022DOI Listing
October 2018

The uroplakin plaque promotes renal structural integrity during congenital and acquired urinary tract obstruction.

Am J Physiol Renal Physiol 2018 10 13;315(4):F1019-F1031. Epub 2018 Jun 13.

Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital , Columbus, Ohio.

Urinary tract obstruction represents a common cause of kidney injury across the human life span, resulting in chronic kidney disease and end-stage renal disease. Yet, the extent of obstructive renal damage can be heterogeneous between individuals, implying the existence of unknown mechanisms that protect against or accelerate kidney injury. In this study, we investigated the role of urothelial remodeling in renal adaptation during congenital and acquired obstruction. In the Megabladder ( Mgb) model of congenital obstruction and unilateral ureteral ligation model of acute obstruction, progressive hydronephrosis is strongly associated with dynamic reorganization of the renal urothelium, which elaborates a continuous uroplakin (Upk) plaque. This led us to postulate that the Upk plaque prevents parenchymal injury during urinary tract obstruction. To test this hypothesis, we interbred Mgb and Upk1b mice, which lack the critical Upk1b subunit for Upk plaque formation. Upk1b; Mgb mice experienced an accelerated onset of bilateral hydronephrosis with severe (>67%) parenchymal loss, leading to renal failure and mortality in adolescence. To investigate the function of the renal Upk plaque during acute obstruction, we destabilized the Upk plaque by Upk1b deletion or genetically depleted Upk cells following unilateral ureteral obstruction. Both of these strategies accelerated renal parenchymal loss following ureteral ligation, attesting to a conserved, stabilizing role for Upk plaque deposition in the acutely obstructed kidney. In aggregate, these complementary experiments provide the first evidence that the Upk plaque confers an essential, protective adaptation to preserve renal parenchymal integrity during congenital and acquired urinary tract obstruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.00173.2018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6230727PMC
October 2018

Intraoperative Onabotulinumtoxin-A Reduces Postoperative Narcotic and Anticholinergic Requirements After Continent Bladder Reconstruction.

Urology 2018 Aug 2;118:183-188. Epub 2018 May 2.

Division of Pediatric Urology, Nationwide Children's Hospital, Columbus, OH.

Objective: To determine if intradetrusor injection of onabotulinumtoxin-A (BTX-A) would reduce postoperative narcotic and anticholinergic requirements in children undergoing open continent bladder reconstruction.

Materials And Methods: After institutional review board approval, we retrospectively reviewed all bladder reconstructions performed. Bladder reconstruction was defined as the following procedures in any combination: bladder neck reconstruction and sling, bladder neck closure, Mitrofanoff, Monti, or bladder augmentation. We identified 15 children who underwent reconstruction with BTX-A injection and compared these with 15 children who did not receive BTX-A. Postoperative narcotic and anticholinergic requirements were recorded as well as length of stay, time to diet, time to return of bowel function, and complications. All medications were converted to morphine mEq/kg per day or mg/kg per day to standardize for patient size and length of stay.

Results: Thirty patients who underwent open bladder reconstruction were included. Fifteen received BTX-A injection and 15 did not. The BTX-A group required significantly less narcotic medication postoperatively compared with the no-BTX-A group (0.32 vs 0.85 morphine mEq/kg per day; P = .0002). The BTX-A group also required significantly less anticholinergic medication compared with the no-BTX-A group (0.22 vs 0.88 mg/kg per day; P = .024). There was no significant difference between the groups with respect to length of stay (98.27 vs 9.287 days; P = .34) or return of bowel function (5.53 vs 4.93 days; P = .994). Complication rate between the groups was similar (P >.99).

Conclusion: Intraoperative injection of BTX-A significantly reduced postoperative narcotic and anticholinergic requirements in patients who underwent open continent bladder reconstruction. This is an encouraging alternative treatment to manage postoperative pain with no associated risk of significant complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2018.04.006DOI Listing
August 2018

Interleukin-6/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection.

Kidney Int 2018 06 21;93(6):1320-1329. Epub 2018 Feb 21.

Research Institute at Nationwide Children's Hospital, Center for Clinical and Translational Research, Columbus, Ohio, USA; Nephrology Section, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA. Electronic address:

The signaling networks regulating antimicrobial activity during urinary tract infection (UTI) are incompletely understood. Interleukin-6 (IL-6) levels increase with UTI severity, but the specific contributions of IL-6 to host immunity against bacterial uropathogens are unknown. To clarify this we tested whether IL-6 activates the Stat3 transcription factor, to drive a program of antimicrobial peptide gene expression in infected urothelium during UTI. Transurethral inoculation of uropathogenic Escherichia coli led to IL-6 secretion, urothelial Stat3 phosphorylation, and activation of antimicrobial peptide transcription, in a Toll-like receptor 4-dependent manner in a murine model of cystitis. Recombinant IL-6 elicited Stat3 phosphorylation in primary urothelial cells in vitro, and systemic IL-6 administration promoted urothelial Stat3 phosphorylation and antimicrobial peptide expression in vivo. IL-6 deficiency led to decreased urothelial Stat3 phosphorylation and antimicrobial peptide mRNA expression following UTI, a finding mirrored by conditional Stat3 deletion. Deficiency in IL-6 or Stat3 was associated with increased formation of intracellular bacterial communities, and exogenous IL-6 reversed this phenotype in IL-6 knockout mice. Moreover, chronic IL-6 depletion led to increased renal bacterial burden and severe pyelonephritis in C3H/HeOuJ mice. Thus, IL-6/Stat3 signaling drives a transcriptional program of antimicrobial gene expression in infected urothelium, with key roles in limiting epithelial invasion and ascending infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2017.12.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5967986PMC
June 2018

Image of the Month: Clinical Features in a Newborn with Covered Cloacal Exstrophy.

European J Pediatr Surg Rep 2017 Jan 13;5(1):e57-e59. Epub 2017 Sep 13.

Center for Colorectal and Pelvic Reconstruction, Nationwide Children's Hospital, Columbus, Ohio, United States.

Cloacal exstrophy is the most severe type of anorectal malformations that belongs to the bladder-exstrophy-epispadias complex of genitourinary malformations. Interestingly, its variant, the covered cloacal exstrophy, is often missed. The clinical findings of this variant may include an imperforate anus, low lying umbilicus, thick pubic bone, and pubic diastasis but with an intact abdominal wall. We present an interesting case of covered cloacal exstrophy with a side-by-side duplicated bladder and discuss important considerations for the time of colostomy creation in the newborn period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/s-0037-1606389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597929PMC
January 2017

Spinal anesthesia for pediatric urological surgery: Reducing the theoretic neurotoxic effects of general anesthesia.

J Pediatr Urol 2017 Aug 14;13(4):396-400. Epub 2017 Jul 14.

Division of Pediatric Urology, Nationwide Children's Hospital, Columbus, OH 43205, USA; Department of Urology, The Ohio State University College of Medicine, Columbus, OH 43212, USA.

Background: Spinal anesthesia (SA) is an effective technique that has been used in children for years. With growing concern with regard to the risks of general anesthesia (GA), we developed a SA program to provide an alternative option. We present our initial experience with this program.

Objective: To implement a SA program at a large tertiary care pediatric center and assess the safety and efficacy of the technique as an alternative to GA for urologic surgery.

Study Design/methods: We prospectively collected data on all children undergoing SA at our institution. We recorded demographics, procedure, time required for placement of the SA, length of surgery, success of lumbar puncture, success of attaining adequate surgical anesthesia, need for supplemental systemic sedation, conversion to GA, and perioperative complications.

Results: SA was attempted in 105 consecutive children (104 boys, 1 girl) with a mean age of 7.4 ± 4.3 months (range 19 days-24 months) and mean weight of 8.3 ± 1.7 kg (range 3.5-13.7). Placement of the SA was successful in 93/105 children (89%). Inability to achieve lumbar puncture (cerebrospinal fluid was not obtained) meant that SA was abandoned in seven (7%) patients and GA was administered. In five patients in whom SA was successful and surgery was begun, 5/93 (5%) required conversion to GA: two because of evisceration of intestine through large hernia defects related to coughing and abdominal irritation, two because of lack of motor blockade despite an adequate sensory block, and one because of an inability to place an intravenous catheter in the lower extremities (required per SA protocol). If necessary, an intravenous catheter can be placed in the upper extremity, but this must be weighed against the fact that the block has already been placed and is of limited duration. Overall, SA was successful (SA was placed and surgery was completed without conversion to GA) in 88/105 children (84%). No additional sedation and no systemic anesthetic agents were required in 75/88 children (85%). The average time required to place the SA was 3.8 ± 2.7 min (range 1-12). The average time for the surgical procedure was 38.3 ± 23.1 min (range 10-122). No patient required conversion to GA because of recession of block. There were no surgical complications.

Discussion/conclusions: SA is a safe and efficacious technique for routine pediatric urological procedures. SA should be considered for cases such as neonatal torsion or patients with significant cardiac or pulmonary comorbidities when the risks of GA are often weighed against the risks of non-intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2017.06.006DOI Listing
August 2017

Inflammation drives renal scarring in experimental pyelonephritis.

Am J Physiol Renal Physiol 2017 01 19;312(1):F43-F53. Epub 2016 Oct 19.

Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio;

Acquired renal scarring occurs in a subset of patients following febrile urinary tract infections and is associated with hypertension, proteinuria, and chronic kidney disease. Limited knowledge of histopathology, immune cell recruitment, and gene expression changes during pyelonephritis restricts the development of therapies to limit renal scarring. Here, we address this knowledge gap using immunocompetent mice with vesicoureteral reflux. Transurethral inoculation of uropathogenic Escherichia coli in C3H/HeOuJ mice leads to renal mucosal injury, tubulointerstitial nephritis, and cortical fibrosis. The extent of fibrosis correlates most significantly with inflammation at 7 and 28 days postinfection. The recruitment of neutrophils and inflammatory macrophages to infected kidneys is proportional to renal bacterial burden. Transcriptome analysis reveals molecular signatures associated with renal ischemia-reperfusion injury, immune cell chemotaxis, and leukocyte activation. This murine model recapitulates the cardinal histopathological features observed in humans with acquired renal scarring following pyelonephritis. The integration of histopathology, quantification of cellular immune influx, and unbiased transcriptional profiling begins to define potential mechanisms of tissue injury during pyelonephritis in the context of an intact immune response. The clear relationship between inflammatory cell recruitment and fibrosis supports the hypothesis that acquired renal scarring arises as a consequence of excessive host inflammation and suggests that immunomodulatory therapies should be investigated to reduce renal scarring in patients with pyelonephritis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajprenal.00471.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5283888PMC
January 2017

Uroepithelial thickening improves detection of vesicoureteral reflux in infants with prenatal hydronephrosis.

J Pediatr Urol 2016 Aug 27;12(4):257.e1-7. Epub 2016 May 27.

Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH, USA; Section of Pediatric Urology, Nationwide Children's Hospital, Columbus, OH, USA. Electronic address:

Introduction: Postnatal evaluation of prenatal hydronephrosis (PNH) often includes a voiding cystourethrogram (VCUG) for VUR assessment. Despite limited supporting data, VCUG is currently recommended if postnatal renal and bladder ultrasound (RBUS) reveals moderate/severe hydronephrosis (HN) or hydroureter (HU). Recent studies have shown VUR is more accurately diagnosed by using certain sonographic findings as criteria for obtaining VCUG. Uroepithelial thickening (UET) of the renal pelvis is a finding associated with high-grade vesicoureteral reflux (HGVUR); however, the clinical significance of UET with PNH has not been studied.

Objective: We sought to determine if the presence of UET implies increased risk for VUR, and to investigate whether UET can improve the test characteristics of RBUS for VUR.

Study Design: We retrospectively analyzed postnatal RBUS and VCUG findings in infants ≤30 days undergoing evaluation for "prenatal hydronephrosis" over an 11-year period. We used logistic regression to identify factors associated with VUR. Test characteristics of RBUS for HGVUR were compared based on the presence of UET and two criteria sets to define abnormal RBUS. Criteria set 1 consisted of HN SFU grade 3-4 and/or HU; criteria set 2 was defined by the presence of two of following: UET, HU, duplication, and/or renal dysmorphia.

Results: Of 135 patients, 39 (29%) had VUR, of whom 16 (41%) had HGVUR. UET was significantly associated with VUR (p < 0.001), and the sensitivity for HGVUR based on UET alone was 94%. On multivariable analysis, UET, HU, duplication, and renal dysmorphia remained significant independent predictors of HGVUR. Compared to criteria 1, using criteria 2 resulted in 43 fewer VCUGs, and significant improvement in sensitivity and specificity for HGVUR (Table).

Discussion: Consistent with previous studies, HN alone on postnatal RBUS has little value in predicting the presence or severity of VUR. This study is the largest known series to evaluate UET in the setting of PNH, and our results demonstrate that UET, as well as HU, duplication and renal dysmorphia, are independent sonographic findings predicting HGVUR. Using our proposed criteria, the probability of HGVUR is fourfold more than the prevalence described in the literature, and importantly, when compared to the criteria recommended by the SFU and AUA, would have resulted in 53% fewer VCUGs while missing zero cases of HGVUR.

Conclusion: In infants with PNH, the sonographic findings of UET, HU, duplication and renal dysmorphia independently indicate greater risk of HGVUR, and the sensitivity and specificity of RBUS for HGVUR is markedly improved when at least two of the four are present.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpurol.2016.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532540PMC
August 2016

Novel Use of Pudendal Neuromodulation in a Pediatric Patient With Caudal Regression and Partial Sacral Agenesis for Refractory Bowel Bladder Dysfunction.

Urology 2016 Aug 28;94:224-6. Epub 2016 Mar 28.

Section of Pediatric Urology, Nationwide Children's Hospital, Columbus, OH; Department of Urology, The Ohio State University Wexner Medical Center, Columbus, OH.

Sacral neuromodulation (SNM) has been used off-label in the United States for over a decade in the pediatric population. Many published studies have demonstrated efficacy with SNM in this population; however, a significant number of children with refractory bowel bladder dysfunction (BBD) also have underlying comorbidities. Children with certain spinal abnormalities pose a problem for the urologist treating BBD. Patients with caudal regression can have various sacral anomalies, making SNM challenging or impossible. We present the first case in the United States of pudendal neuromodulation in a pediatric BBD patient with caudal regression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.urology.2016.03.006DOI Listing
August 2016

Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis.

Kidney Int 2016 Mar 23;89(3):612-24. Epub 2015 Dec 23.

Molecular and Human Genetics, Nationwide Children's Hospital, Columbus, Ohio, USA; Division of Anatomy, Ohio State University, Columbus, Ohio, USA.

Proper development and maintenance of urothelium is critical to its function. Uroplakins are expressed in developing and mature urothelium where they establish plaques associated with the permeability barrier. Their precise functional role in development and disease is unknown. Here, we disrupted Upk1b in vivo where its loss resulted in urothelial plaque disruption in the bladder and kidney. Upk1b(RFP/RFP) bladder urothelium appeared dysplastic with expansion of the progenitor cell markers, Krt14 and Krt5, increased Shh expression, and loss of terminal differentiation markers Krt20 and uroplakins. Upk1b(RFP/RFP) renal urothelium became stratified with altered cellular composition. Upk1b(RFP/RFP) mice developed age-dependent progressive hydronephrosis. Interestingly, 16% of Upk1b(RFP/RFP) mice possessed unilateral duplex kidneys. Our study expands the role of uroplakins, mechanistically links plaque formation to urinary tract development and function, and provides a tantalizing connection between congenital anomalies of the kidney and urinary tract along with functional deficits observed in a variety of urinary tract diseases. Thus, kidney and bladder urothelium are regionally distinct and remain highly plastic, capable of expansion through tissue-specific progenitor populations. Furthermore, Upk1b plays a previously unknown role in early kidney development representing a novel genetic target for congenital anomalies of the kidney and urinary tract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2015.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757817PMC
March 2016

Expression and Significance of the HIP/PAP and RegIIIγ Antimicrobial Peptides during Mammalian Urinary Tract Infection.

PLoS One 2015 10;10(12):e0144024. Epub 2015 Dec 10.

Division of Nephrology, Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, United States of America.

Recent evidence indicates that antimicrobial peptides (AMPs) serve key roles in defending the urinary tract against invading uropathogens. To date, the individual contribution of AMPs to urinary tract host defense is not well defined. In this study, we identified Regenerating islet-derived 3 gamma (RegIIIγ) as the most transcriptionally up-regulated AMP in murine bladder transcriptomes following uropathogenic Escherichia coli (UPEC) infection. We confirmed induction of RegIIIγ mRNA during cystitis and pyelonephritis by quantitative RT-PCR. Immunoblotting demonstrates increased bladder and urinary RegIIIγ protein levels following UPEC infection. Immunostaining localizes RegIIIγ protein to urothelial cells of infected bladders and kidneys. Human patients with UTI have increased urine concentrations of the orthologous Hepatocarcinoma-Intestine-Pancreas / Pancreatitis Associated Protein (HIP/PAP) compared to healthy controls. Recombinant RegIIIγ protein does not demonstrate bactericidal activity toward UPEC in vitro, but does kill Staphylococcus saprophyticus in a dose-dependent manner. Kidney and bladder tissue from RegIIIγ knockout mice and wild-type mice contain comparable bacterial burden following UPEC and Gram-positive UTI. Our results demonstrate that RegIIIγ and HIP/PAP expression is induced during human and murine UTI. However, their specific function in the urinary tract remains uncertain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144024PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4675559PMC
July 2016