OXGR1 is a candidate disease gene for human calcium oxalate nephrolithiasis.

PURPOSE: Nephrolithiasis (NL) affects 1 in 11 individuals worldwide, leading to significant patient morbidity. NL is associated with nephrocalcinosis (NC), a risk factor for chronic kidney disease. Causative genetic variants are detected in 11% to 28% of NL and/or NC, suggesting that additional NL/NC-associated genetic loci await discovery. Therefore, we employed genomic approaches to discover novel genetic forms of NL/NC. METHODS: Exome sequencing and directed sequencing of the OXGR1 locus were performed in a worldwide NL/NC cohort. Putatively deleterious, rare OXGR1 variants were functionally characterized. RESULTS: Exome sequencing revealed a heterozygous OXGR1 missense variant (c.371T>G, p.L124R) cosegregating with calcium oxalate NL and/or NC disease in an autosomal dominant inheritance pattern within a multigenerational family with 5 affected individuals. OXGR1 encodes 2-oxoglutarate (α-ketoglutarate [AKG]) receptor 1 in the distal nephron. In response to its ligand AKG, OXGR1 stimulates the chloride-bicarbonate exchanger, pendrin, which also regulates transepithelial calcium transport in cortical connecting tubules. Strong amino acid conservation in orthologs and paralogs, severe in silico prediction scores, and extreme rarity in exome population databases suggested that the variant was deleterious. Interrogation of the OXGR1 locus in 1107 additional NL/NC families identified 5 additional deleterious dominant variants in 5 families with calcium oxalate NL/NC. Rare, potentially deleterious OXGR1 variants were enriched in patients with NL/NC compared with Exome Aggregation Consortium controls (χ2 = 7.117, P = .0076). Wild-type OXGR1-expressing Xenopus oocytes exhibited AKG-responsive Ca2+ uptake. Of 5 NL/NC-associated missense variants, 5 revealed impaired AKG-dependent Ca2+ uptake, demonstrating loss of function. CONCLUSION: Rare, dominant loss-of-function OXGR1 variants are associated with recurrent calcium oxalate NL/NC disease.

Hybrid Clinics: A New Model for Ambulatory Care to Reduce Infection Risk.

Objectives: To assess the viability of a hybrid clinic model combining in-person examination with video-based consultation to minimize viral transmission risk. Methods: Data were collected prospectively in a pediatric urology clinic for in-person visits from January to April 2018 ("classic") and hybrid visits from October to December 2020 of the COVID-19 pandemic ("hybrid"). Variables included provider, diagnosis, patient type, time of day, prior surgery, postoperative status, and decision-making for surgery. The primary outcome was "room time" or time in-person. The secondary outcome was "total time" or visit duration. Proportion of visits involving close contact (room time ≥15 min) was assessed. Univariate analyses were performed using the Wilcoxon rank-sum test and Fisher's exact test. Mixed models were fitted for visit approach and other covariates as fixed effects and provider as random effect. Results: Data were collected for 346 visits (256 classic, 90 hybrid). Hybrid visits were associated with less room time (median 3 min vs. 10 min, p < 0.001) but greater total time (median 13.5 min vs. 10 min, p = 0.001) as compared with classic visits. On multivariate analysis, hybrid visits were associated with 3 min less room time (95% confidence intervals [CIs]: -5.3 to -1.7, p < 0.001) but 3.8 min more total time (95% CI: 1.5-6.1, p = 0.001). Close contact occurred in 6.7% of hybrid visits, as compared with 34.8% of classic visits (p < 0.001). Conclusions: Hybrid clinic visits reduce room time as compared with classic visits. This approach overcomes the examination limitations of telemedicine while minimizing viral transmission, and represents a viable model for ambulatory care whenever close contact carries infection risk.

Comparing Pediatric Ureteroscopy Outcomes with SuperPulsed Thulium Fiber Laser and Low-Power Holmium:YAG Laser.

PURPOSE: The thulium fiber laser is a promising new lithoptripsy technology never before studied in the pediatric population. Our center adopted the first platform in North America, the SuperPulsed thulium fiber laser (SPTF). We aimed to compare outcomes in pediatric ureteroscopy using the SPTF to those using the gold standard, low-power holmium:yttrium-aluminum-garnet (Ho:YAG) laser. MATERIALS AND METHODS: This is a retrospective, consecutive cohort study of unilateral ureteroscopy with laser lithotripsy performed in pediatric patients from 2016 to 2021 as an early adopter of the SPTF. Thirty-day complications and stone-free status, defined as the absence of a stone fragment on followup imaging within 90 days, were analyzed using logistic regression. Operative times were compared using linear regression. Propensity scores for use of SPTF were used in regression analyses to account for potential cohort imbalance. RESULTS: A total of 125 cases were performed in 109 pediatric patients: 93 with Ho:YAG and 32 with SPTF. No significant difference was noted in age (p=0.2), gender (p=0.6), stone burden (p >0.9) or stone location (p=0.1). The overall stone-free rate was 62%; 70% with SPTF and 59% with Ho:YAG. The odds of having a residual stone fragment were significantly lower with SPTF than with Ho:YAG (OR=0.39, 95% CI: 0.19-0.77, p=0.01). There was no significant difference in operative time (p=0.8). Seven (25%) complications were noted with SPTF and 19 (22%) with Ho:YAG (p=0.6). CONCLUSIONS: The SPTF laser was associated with a higher stone-free rate than the low-power Ho:YAG laser without compromising operative time and safety.

Malignancy Yield of Testis Pathology in Older Boys and Adolescents with Cryptorchidism.

PURPOSE: We performed a retrospective, single-institution study to characterize the pathological findings of testis tissue specimens from older boys and adolescents with cryptorchidism. MATERIALS AND METHODS: With institutional review board approval, pathology reports were obtained for testicular specimens from patients age 10 years or older at a pediatric hospital from 1994 to 2016. Reports were excluded if they lacked clinical records, lacked testicular parenchyma, were from a descended testis or were from a patient with differences of sexual development. Variables of interest included age, testis location, procedure and pathological findings. Presence of malignancy among intra-abdominal versus extra-abdominal undescended testes was compared using Fisher's Exact Test. RESULTS: Seventy-one patients met inclusion criteria. The median age was 15.3 years (range 10.1-27.7). None had a history of testicular malignancy. Forty-five unilateral orchiectomies, 22 unilateral orchiopexies with biopsy and 4 bilateral procedures were performed. Seventeen testes (22.7%) were intra-abdominal, 42 (56.0%) were in the inguinal canal, 9 (12.0%) were at the external inguinal ring, 3 (4.0%) were in the superficial inguinal pouch and 4 (5.3%) were in the scrotum. Malignancy was detected in 2/71 patients (2.8%). By location, 2/16 patients (12.5%) with intra-abdominal testis and 0/55 patients (0%) with extra-abdominal testis demonstrated malignancy (p=0.048). CONCLUSIONS: Among males with cryptorchidism ages 10 years and older without differences of sexual development, 2/16 patients with intra-abdominal testis and 0/55 patients with extra-abdominal testis demonstrated malignancy. In older boys and adolescents, orchiectomy or biopsy is indicated for intra-abdominal testes but may not be necessary for extra-abdominal undescended testes.

Dietary Risk Factors for Pediatric Kidney Stones: A Case-Control Study.

PURPOSE: Data are scarce regarding dietary risk factors for pediatric nephrolithiasis. Our objective was to perform a case-control study (nonmatched) of the association of dietary nutrients with pediatric urolithiasis. MATERIALS AND METHODS: We obtained dietary information from pediatric urolithiasis patients (from stone clinic in 2013-2016) and healthy controls (well-child visit at primary care in 2011-2012). Survey results were converted to standard nutrient intakes. Children younger than 5 years of age and those with extreme calorie intake values (<500 or >5,000 kcal/day) were excluded. The association of individual nutrients with urolithiasis was assessed by bivariate analysis results and machine-learning methods. A multivariable logistic regression model was fitted using urolithiasis as the outcome. RESULTS: We included 285 patients (57 stones/228 controls). Mean±SD age was 8.9±3.6 years (range 5-20). Of the patients 47% were male. After adjusting for age, sex, body mass index (obese/overweight/normal), calorie intake and oxalate, urolithiasis was associated with higher dietary sodium (OR=2.43 [95% CI=1.40-4.84] per quintile increase, p=0.004), calcium (OR=1.73 [95% CI=1.07-3.00] per quintile increase, p=0.034) and beta carotene (OR=2.01 [95% CI=1.06-4.18] per quintile increase, p=0.042), and lower potassium (OR=0.31 [95% CI=0.13-0.63] per quintile increase, p=0.003). Sensitivity analysis was performed by removing oxalate from the model and limiting the sample to patients aged 5-13 years, with similar results. CONCLUSIONS: In our cohort, higher dietary intake of calcium, sodium and beta carotene, and lower potassium intake were associated with pediatric urolithiasis. This is the first study using a detailed dietary survey to identify dietary risk factors for pediatric urolithiasis. Further research is warranted to delineate the mechanisms and to generate a lower risk diet profile for pediatric urolithiasis.

Normative values for ureteral diameter in children.

BACKGROUND: Assessment of the ureter is a fundamental part of the radiologic evaluation of the urinary tract. Abnormal ureteral dilation warrants further investigation to assess the etiology, which includes obstruction and/or reflux. Despite this fundamental need, there are no established normative values in children based on imaging. OBJECTIVE: To provide normative values for ureteral diameter in pediatric patients with age-related ranges. MATERIALS AND METHODS: We retrospectively reviewed all magnetic resonance (MR) urography studies and chose only normal ureters for assessment. The images were analyzed on commercially available software to assess maximum internal diameter. Manual measurements were done in cases where the images were below the resolution for automated assessment. Maximum intraluminal ureteral diameters were measured in upper, mid and lower thirds and the average of the three maximum ureteral diameters was used to obtain the average widest internal ureteral diameter. Multivariable linear regression was performed to test the association between the calculated diameter and gender. Differences in sizes between the left and right ureter were assessed using paired Wilcoxon signed rank test. RESULTS: One hundred twenty-one MR urography studies were selected, which included 160 ureter units. The diameter increases progressively with age, ranging from 3.2 mm during infancy to 5.0 mm in patients older than 16 years of age. After 9 years of age, the average widest internal ureteral diameter is slightly larger in males compared to females (odds ratio [OR]=1.91, 95% confidence interval [CI] [1.63, 2.25], P<0.0001). The right ureter was slightly larger than the left (3.9 mm vs. 3.7 mm, P=0.004) among 39 patients in whom both right and left ureter units were included. The average mid ureteral diameter is widest, followed by the distal third then proximal third. CONCLUSION: We present the normative values for the average widest internal ureteral diameter based on laterality and different segments. In the pediatric population, 3.8 mm should be considered the average widest internal ureteral diameter.

Changes in Clinical Presentation and Renal Outcomes among Children with Febrile Urinary Tract Infection: 2005 vs 2015.

PURPOSE: Recent studies have demonstrated trends of decreasing voiding cystourethrogram utilization rates and delayed vesicoureteral reflux diagnosis in some children. It is possible that such delays could lead to more children sustaining repeated episodes of febrile urinary tract infection, and potential kidney injury, prior to diagnosis and treatment. MATERIALS AND METHODS: Using single institutional, cross-sectional cohorts of patients in 2 time periods (2005 and 2015), we compared clinical presentation and renal outcomes among patients 13 years and younger with history of febrile urinary tract infection presenting for initial voiding cystourethrogram. Outcomes included 1) recurrent urinary tract infection, 2) presence of vesicoureteral reflux, 3) grade of vesicoureteral reflux, and 4) renal scarring. Associations between year of presentation and outcomes of recurrent urinary tract infection and vesicoureteral reflux diagnosis were evaluated using multivariable logistic regression models. For the outcome of renal scarring, a logistic regression model was fitted for propensity score matched cohorts. RESULTS: Compared to children presenting in 2005, those in 2015 had 3 times the odds of recurrent urinary tract infection (OR 3.01, 95% CI 2.18-4.16, p <0.0001). Time period was not associated with the odds of vesicoureteral reflux (OR 0.98, 95% CI 0.77-1.23, p=0.85). Those in 2015 were more likely to present with vesicoureteral reflux grade >3 (OR 2.22, 95% CI 1.13-4.34, p=0.02) but not vesicoureteral reflux grade >2 (OR 1.11, 95% CI 0.74-1.67, p=0.60). Renal scarring was more common among children presenting in 2015 (OR 2.9, 95% CI 1.03-8.20, p=0.04). CONCLUSIONS: Compared to 2005, children presenting in 2015 for post-urinary tract infection voiding cystourethrogram have increased likelihood of recurrent urinary tract infection and renal scarring, despite similar likelihood of vesicoureteral reflux diagnosis.

Antireflux Surgery at National Surgical Quality Improvement Program-Pediatric Hospitals.

PURPOSE: This study aims to examine contemporary practice patterns and compare short-term outcomes for vesicoureteral reflux procedures (ureteral reimplant/endoscopic injection) using National Surgical Quality Improvement Program-Pediatric data. MATERIALS AND METHODS: Procedure-specific variables for antireflux surgery were developed to capture data not typically collected in National Surgical Quality Improvement Program-Pediatric (eg vesicoureteral reflux grade, urine cultures, 31-60-day followup). Descriptive statistics were performed, and logistic regression assessed associations between patient/procedural factors and outcomes (urinary tract infection, readmissions, unplanned procedures). RESULTS: In total, 2,842 patients (median age 4 years; 76% female; 68% open reimplant, 6% minimally invasive reimplant, 25% endoscopic injection) had procedure-specific variables collected from July 2016 through June 2018. Among 88 hospitals, a median of 24.5 procedures/study period were performed (range 1-148); 95% performed ≥1 open reimplant, 30% ≥1 minimally invasive reimplant, and 70% ≥1 endoscopic injection, with variability by hospital. Two-thirds of patients had urine cultures sent preoperatively, and 76% were discharged on antibiotics. Outcomes at 30 days included emergency department visits (10%), readmissions (4%), urinary tract infections (3%), and unplanned procedures (2%). Over half of patients (55%) had optional 31-60-day followup, with additional outcomes (particularly urinary tract infections) noted. Patients undergoing reimplant were younger, had higher reflux grades, and more postoperative occurrences than patients undergoing endoscopic injections. CONCLUSIONS: Contemporary data indicate that open reimplant is still the most common antireflux procedure, but procedure distribution varies by hospital. Emergency department visits are common, but unplanned procedures are rare, particularly for endoscopic injection. These data provide basis for comparing short-term complications and developing standardized perioperative pathways for antireflux surgery.

Pattern recognition algorithm to identify detrusor overactivity on urodynamics.

AIMS: Detrusor overactivity (DO) of the bladder is a finding on urodynamic studies (UDS) that often correlates with lower urinary tract symptoms and drives management. However, UDS interpretation remains nonstandardized. We sought to develop a mathematical model to reliably identify DO in UDS. METHODS: We utilized UDS archive files for studies performed at our institution between 2013 and 2019. Raw tracings of vesical pressure, abdominal pressure, detrusor pressure, infused volume, and all annotations during UDS were obtained. Patients less than 1 year old, studies with calibration issues, or those with significant artifacts were excluded. In the training set, five representative DO patterns were identified. Candidate Pdet signal segments were matched to representative DO patterns. Manifold learning and dynamic time warping algorithms were used. Five-fold cross validation (CV) was used to evaluate the performance. RESULTS: A total of 799 UDS studies were included. The median age was 9 years (range, 1-33). There were 1,742 DO events that did not overlap with annotated artifacts (cough, cry, valsalva, movements). The AUC of the training sets from the five-fold CV was 0.84 ± 0.01. The five-fold CV leads to an overall accuracy 81.35%, and sensitivity and specificity of detecting DO events are 76.92% and 81.41%, respectively, in the testing set. CONCLUSIONS: Our predictive model using machine learning algorithms provides promising performance to facilitate automated identification of DO in UDS. This would allow for standardization and potentially more reliable UDS interpretation. Signal processing and machine learning interpretation of the other components of UDS are forthcoming.

Telemedicine for Pediatric Urological Postoperative Care is Safe, Convenient and Economical.

PURPOSE: We compared virtual visits, ie remote patient encounters, via a live video system, with conventional in-person visits with respect to clinical outcomes, family experience and costs in a pediatric urology surgical population. MATERIALS AND METHODS: Patients were enrolled in a prospective cohort study comparing postoperative virtual and in-person visits during a 4-month period in 2018. Appointment status and time metrics were tracked. The primary outcome was the safety of virtual visits, assessed by comparing the number of additional in-person visits, emergency department encounters and hospital readmissions. Secondary outcomes included the family assessment of the encounter and associated costs. After each visit families were prompted to complete a survey that assessed missed work/school and direct costs. Opportunity cost was estimated using reported missed work time, average national hourly wage and visit duration. RESULTS: Overall 107 virtual and 100 in-person postoperative visits were completed. There was no difference in patient characteristics, appointment compliance or clinical outcomes between the cohorts. Travel and waiting for care accounted for 98.4% of the total time spent for an in-person visit. With the virtual visit significantly less work and school were missed by parents and children, respectively. The opportunity costs associated with an in-person visit were computed at $23.75 per minute of face time with a physician, compared to $1.14 for a virtual visit. CONCLUSIONS: For pediatric postoperative care virtual visits are associated with shorter wait times, decreased missed work and school, and clinical outcomes similar to those of in-person visits. Telemedicine appears to reduce the costs associated with these brief but important encounters.

Interobserver Reliability of the Antenatal Consensus Classification System for Urinary Tract Dilatation.

OBJECTIVES: The consensus classification system for urinary tract dilatation (UTD) was designed to be more objective and reproducible than previously used systems. We sought to evaluate interobserver reliability of UTD components and overall scores in a prenatal population undergoing third-trimester ultrasound examinations. METHODS: We retrospectively identified patients who underwent antenatal ultrasound examinations for UTD between 28 and 40 weeks' gestation. All images from individual studies of 300 fetuses were reviewed independently by 5 experienced sonologists (1 maternal-fetal medicine specialist and 4 radiologists). Urinary tract dilatation scores (normal, A1, or A2/3) and Society for Fetal Urology (SFU) scores were assigned. Interobserver agreement between raters was evaluated with the Fleiss κ statistic. RESULTS: Overall interobserver agreement for the antenatal UTD risk score showed substantial agreement among all 5 readers (κ = 0.657 [95% confidence interval, 0.632, 0.683]; P < .001). All 5 readers applied the same UTD risk score in 53.7% of cases. Some variability in the antenatal UTD score and individual elements was observed. At least 2 UTD risk scores were assigned to a specific individual patient in 46.3% of cases (139 of 300), and all 3 UTD risk scores were assigned to a specific individual patient in 1.7% of cases (5 of 300). In 18.0% of cases (54 of 300), at least 2 readers assigned a UTD score different from that assigned by the other readers. Agreement was lowest for parenchymal appearance (κ = 0.225). Agreement for the SFU system was fair (κ = 0.368; P < .001). CONCLUSIONS: Interobserver agreement for the antenatal UTD grading system was substantial. Compared to the SFU system, the antenatal UTD system showed better agreement among readers.

Mutations in SLC26A1 Cause Nephrolithiasis.

Nephrolithiasis, a condition in which urinary supersaturation leads to stone formation in the urinary system, affects about 5%-10% of individuals worldwide at some point in their lifetime and results in significant medical costs and morbidity. To date, mutations in more than 30 genes have been described as being associated with nephrolithiasis, and these mutations explain about 15% of kidney stone cases, suggesting that additional nephrolithiasis-associated genes remain to be discovered. To identify additional genes whose mutations are linked to nephrolithiasis, we performed targeted next-generation sequencing of 18 hypothesized candidate genes in 348 unrelated individuals with kidney stones. We detected biallelic mutations in SLC26A1 (solute carrier family 26 member 1) in two unrelated individuals with calcium oxalate kidney stones. We show by immunofluorescence, immunoblotting, and glycosylation analysis that the variant protein mimicking p.Thr185Met has defects in protein folding or trafficking. In addition, by measuring anion exchange activity of SLC26A1, we demonstrate that all the identified mutations in SLC26A1 result in decreased transporter activity. Our data identify SLC26A1 mutations as causing a recessive Mendelian form of nephrolithiasis.

The Use of Telemedicine for the Postoperative Urological Care of Children: Results of a Pilot Program.

PURPOSE: For postoperative visits, which are often brief interactions between family and clinician, patients may prefer the convenience of receiving postoperative care from home. We evaluated the feasibility of telemedicine for postoperative encounters in pediatric urology. MATERIALS AND METHODS: We performed a prospective telemedicine pilot study during an implementation period from November 10, 2017 to March 22, 2018. All postoperative patients deemed eligible by 1 of 4 urologists were offered enrollment in the telemedicine program. Enrollees underwent at least 1 virtual visit within 6 weeks of surgery. Technical difficulties and the number of unscheduled visits and readmissions were noted. After each virtual evaluation the family and clinician were prompted to complete a survey pertaining to perceptions of the telemedicine experience, including how effective the virtual visit was in delivering care. For each virtual visit with a urologist we estimated roundtrip travel cost and time. RESULTS: There was 96% technical success when using the software. A total of 125 postoperative virtual visits were completed in 83 patients. Median age of the children was 3.4 years and 87% were boys. Clinicians found that the virtual visit was "very effective" in 86% of cases, delivering the same care that they would have provided during a visit in person. Families were estimated to have saved a mean $150 travel cost and a median of 113 minutes of travel time per visit. No adverse postoperative outcomes were observed. CONCLUSIONS: This pilot study demonstrates that telemedicine can be successfully implemented in the postoperative care of pediatric urology patients.

Interobserver and Intra-Observer Reliability of the Urinary Tract Dilation Classification System in Neonates: A Multicenter Study.

PURPOSE: The Urinary Tract Dilation classification system was designed to be more objective and reproducible than currently available grading systems. We evaluated the reliability and consistency of the system in newborns. MATERIALS AND METHODS: Of 1,046 infants 0 to 90 days old undergoing ultrasound for hydronephrosis 243 were randomly selected for study inclusion. Seven readers (4 radiologists and 3 urologists) at 4 institutions classified complete, de-identified ultrasound studies on a Web based platform. Interobserver and intra-observer agreement was evaluated using the Fleiss kappa statistic. RESULTS: Interobserver agreement for Urinary Tract Dilation risk score was moderate among the 7 readers (kappa = 0.421, 95% CI 0.404-0.438). Interobserver agreement using the Society for Fetal Urology scale was worse than with the Urinary Tract Dilation classification (kappa = 0.344, 95% CI 0.330-0.359). All 7 readers assigned the same Urinary Tract Dilation score in 19.3% of cases (47 of 243). In 38.7% of cases (94 of 243) at least 3 readers assigned a Urinary Tract Dilation score different from that assigned by the other readers. In 7% of cases (17 of 243) at least 3 readers assigned a score of P0/P1, while at least 3 readers scored the same cases as P2/P3. At least 3 different Urinary Tract Dilation risk scores were assigned to the same patient in 30.45% of patients (74 of 243). Among individual Urinary Tract Dilation elements calyceal dilatation and bladder status had the highest disagreement. Five readers regraded 80 cases and agreed with their previous Urinary Tract Dilation risk score in 63.8% to 75.0% of cases (kappa 0.458 to 0.729). CONCLUSIONS: Interobserver agreement using the Urinary Tract Dilation grading system is fair to moderate, with variable agreement on individual elements of the system. Agreement was higher for the Urinary Tract Dilation system compared to the Society for Fetal Urology scale.

Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis.

The incidence of nephrolithiasis continues to rise. Previously, we showed that a monogenic cause could be detected in 11.4% of individuals with adult-onset nephrolithiasis or nephrocalcinosis and in 16.7-20.8% of individuals with onset before 18 years of age, using gene panel sequencing of 30 genes known to cause nephrolithiasis/nephrocalcinosis. To overcome the limitations of panel sequencing, we utilized whole exome sequencing in 51 families, who presented before age 25 years with at least one renal stone or with a renal ultrasound finding of nephrocalcinosis to identify the underlying molecular genetic cause of disease. In 15 of 51 families, we detected a monogenic causative mutation by whole exome sequencing. A mutation in seven recessive genes (AGXT, ATP6V1B1, CLDN16, CLDN19, GRHPR, SLC3A1, SLC12A1), in one dominant gene (SLC9A3R1), and in one gene (SLC34A1) with both recessive and dominant inheritance was detected. Seven of the 19 different mutations were not previously described as disease-causing. In one family, a causative mutation in one of 117 genes that may represent phenocopies of nephrolithiasis-causing genes was detected. In nine of 15 families, the genetic diagnosis may have specific implications for stone management and prevention. Several factors that correlated with the higher detection rate in our cohort were younger age at onset of nephrolithiasis/nephrocalcinosis, presence of multiple affected members in a family, and presence of consanguinity. Thus, we established whole exome sequencing as an efficient approach toward a molecular genetic diagnosis in individuals with nephrolithiasis/nephrocalcinosis who manifest before age 25 years.

Antimicrobial prophylaxis for children with vesicoureteral reflux.

BACKGROUND: Children with febrile urinary tract infection commonly have vesicoureteral reflux. Because trial results have been limited and inconsistent, the use of antimicrobial prophylaxis to prevent recurrences in children with reflux remains controversial. METHODS: In this 2-year, multisite, randomized, placebo-controlled trial involving 607 children with vesicoureteral reflux that was diagnosed after a first or second febrile or symptomatic urinary tract infection, we evaluated the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences (primary outcome). Secondary outcomes were renal scarring, treatment failure (a composite of recurrences and scarring), and antimicrobial resistance. RESULTS: Recurrent urinary tract infection developed in 39 of 302 children who received prophylaxis as compared with 72 of 305 children who received placebo (relative risk, 0.55; 95% confidence interval [CI], 0.38 to 0.78). Prophylaxis reduced the risk of recurrences by 50% (hazard ratio, 0.50; 95% CI, 0.34 to 0.74) and was particularly effective in children whose index infection was febrile (hazard ratio, 0.41; 95% CI, 0.26 to 0.64) and in those with baseline bladder and bowel dysfunction (hazard ratio, 0.21; 95% CI, 0.08 to 0.58). The occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively). Among 87 children with a first recurrence caused by Escherichia coli, the proportion of isolates that were resistant to trimethoprim-sulfamethoxazole was 63% in the prophylaxis group and 19% in the placebo group. CONCLUSIONS: Among children with vesicoureteral reflux after urinary tract infection, antimicrobial prophylaxis was associated with a substantially reduced risk of recurrence but not of renal scarring. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; RIVUR ClinicalTrials.gov number, NCT00405704.).

Blunt Abdominal Trauma from Motor Vehicle Collisions from 2007 to 2011: Renal Injury Probability and Severity in Children versus Adults.

PURPOSE: There are sparse data directly comparing the probability of renal injury in children and adults. The kidney of the child is believed to be more susceptible to blunt injury for a variety of anatomical reasons. In a large cohort we tested the hypothesis that the pediatric kidney is more susceptible to any renal injury and to higher grade injury. MATERIALS AND METHODS: We queried the NTDB® (National Trauma Data Bank®) on all hospital admissions following motor vehicle collisions in a pediatric population (age less than 21 years) and a referent adult population (age 30 to 50 years). Of 111,172 children who were admitted after motor vehicle collisions 1,093 had renal injury. RESULTS: Of the 111,172 children admitted to the hospital following motor vehicle collisions 59,385 had abdominal trauma and 1,093 had renal injury. In a multivariate logistic model adjusting for overall ISS (Injury Severity Score), region, year, driver/passenger status, presence of restraint or an airbag, we found that children had 48% higher odds of renal injury compared to adults ages 30 to 50 years (OR 1.48, 95% CI 1.32-1.66, p <0.001). Furthermore, children were at 33% higher risk for high grade renal injury (OR 1.33, 95% CI 1.05-1.69, p = 0.919). The effect remained when restricting analysis to patients with concomitant liver and spleen injuries (p <0.001). CONCLUSIONS: In a large national cohort of children, blunt renal injury following motor vehicle collisions is rare but substantially more common than in adults. The odds of high grade renal injury are approximately 50% higher in children. A greater index of suspicion and a lower threshold for renal imaging is prudent for children with blunt abdominal trauma from motor vehicle collisions.

Utility Estimation for Pediatric Vesicoureteral Reflux: Methodological Considerations Using an Online Survey Platform.

PURPOSE: The advent of online task distribution has opened a new avenue for efficiently gathering community perspectives needed for utility estimation. Methodological consensus for estimating pediatric utilities is lacking, with disagreement over whom to sample, what perspective to use (patient vs parent) and whether instrument induced anchoring bias is significant. We evaluated what methodological factors potentially impact utility estimates for vesicoureteral reflux. MATERIALS AND METHODS: Cross-sectional surveys using a time trade-off instrument were conducted via the Amazon Mechanical Turk® (https://www.mturk.com) online interface. Respondents were randomized to answer questions from child, parent or dyad perspectives on the utility of a vesicoureteral reflux health state and 1 of 3 "warm-up" scenarios (paralysis, common cold, none) before a vesicoureteral reflux scenario. Utility estimates and potential predictors were fitted to a generalized linear model to determine what factors most impacted utilities. RESULTS: A total of 1,627 responses were obtained. Mean respondent age was 34.9 years. Of the respondents 48% were female, 38% were married and 44% had children. Utility values were uninfluenced by child/personal vesicoureteral reflux/urinary tract infection history, income or race. Utilities were affected by perspective and were higher in the child group (34% lower in parent vs child, p <0.001, and 13% lower in dyad vs child, p <0.001). Vesicoureteral reflux utility was not significantly affected by the presence or type of time trade-off warm-up scenario (p = 0.17). CONCLUSIONS: Time trade-off perspective affects utilities when estimated via an online interface. However, utilities are unaffected by the presence, type or absence of warm-up scenarios. These findings could have significant methodological implications for future utility elicitations regarding other pediatric conditions.

Imaging in the diagnosis of pediatric urolithiasis.

Pediatric urolithiasis is an important and increasingly prevalent cause of pediatric morbidity and hospital admission. Ultrasound (US) is the recommended primary imaging modality for suspected urolithiasis in children. There is, however, widespread use of CT as a first-line study for abdominal pain in many institutions involved in pediatric care. The objective of this review is to outline state-of-the-art imaging modalities and methods for diagnosing urolithiasis in children. The pediatric radiologist plays a key role in ensuring that the appropriate imaging modality is performed in the setting of suspected pediatric urolithiasis. Our proposed imaging algorithm starts with US, and describes the optimal technique and indications for the use of CT. We emphasize the importance of improved communication with a greater collaborative approach between pediatric and general radiology departments so children undergo the appropriate imaging evaluation.

Surgical Management of Stones: American Urological Association/Endourological Society Guideline, PART II.

PURPOSE: This Guideline is intended to provide a clinical framework for the surgical management of patients with kidney and/or ureteral stones. The summary presented herein represents Part II of the two-part series dedicated to Surgical Management of Stones: American Urological Association/Endourological Society Guideline. Please refer to Part I for introductory information and a discussion of pre-operative imaging and special cases. MATERIALS AND METHODS: A systematic review of the literature (search dates 1/1/1985 to 5/31/2015) was conducted to identify peer-reviewed studies relevant to the surgical management of stones. The review yielded an evidence base of 1,911 articles after application of inclusion/exclusion criteria. These publications were used to create the Guideline statements. Evidence-based statements of Strong, Moderate, or Conditional Recommendation were developed based on benefits and risks/burdens to patients. Additional directives are provided as Clinical Principles and Expert Opinions when insufficient evidence existed. RESULTS: The Panel identified 12 adult Index Patients to represent the most common cases seen in clinical practice. Three additional Index Patients were also created to describe the more commonly encountered special cases, including pediatric and pregnant patients. With these patients in mind, Guideline statements were developed to aid the clinician in identifying optimal management. CONCLUSIONS: Proper treatment selection, which is directed by patient- and stone-specific factors, remains the greatest predictor of successful treatment outcomes. This Guideline is intended for use in conjunction with the individual patient's treatment goals. In all cases, patient preferences and personal goals should be considered when choosing a management strategy.