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Introduction: Much of the higher risk for end-stage kidney disease (ESKD) in African American individuals relates to ancestry-specific variation in the apolipoprotein L1 gene (APOL1). Relative to kidneys from European American deceased-donors, kidneys from African American deceased-donors have shorter allograft survival and African American living-kidney donors more often develop ESKD. The National Institutes of Health (NIH)–sponsored APOL1 Long-term Kidney Transplantation Outcomes Network (APOLLO) is prospectively assessing kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes. Methods: APOLLO will evaluate outcomes from 2614 deceased kidney donor-recipient pairs, as well as additional living-kidney donor-recipient pairs and unpaired deceased-donor kidneys. Results: The United Network for Organ Sharing (UNOS), Association of Organ Procurement Organizations, American Society of Transplantation, American Society for Histocompatibility and Immunogenetics, and nearly all U.S. kidney transplant programs, organ procurement organizations (OPOs), and histocompatibility laboratories are participating in this observational study. APOLLO employs a central institutional review board (cIRB) and maintains voluntary partnerships with OPOs and histocompatibility laboratories. A Community Advisory Council composed of African American individuals with a personal or family history of kidney disease has advised the NIH Project Office and Steering Committee since inception. UNOS is providing data for outcome analyses. Conclusion: This article describes unique aspects of the protocol, design, and performance of APOLLO. Results will guide use of APOL1 genotypic data to improve the assessment of quality in deceased-donor kidneys and could increase numbers of transplanted kidneys, reduce rates of discard, and improve the safety of living-kidney donation. Keywords: African Americans, APOL1, chronic kidney disease, graft failure, kidney transplantation, outcomes

Background: The objective of this study was to compare the accuracy of available tests for pyuria, including newer automated tests, and to examine the implications of requiring them for the diagnosis of urinary tract infections (UTIs)., Methods: We included children between 1 and 36 months of age undergoing bladder catheterization for suspected UTIs who presented to 1 of 3 pediatric centers. Using a positive urine culture result as the reference standard, we compared the sensitivity of 5 modalities for assessing pyuria at the cutoffs most often used clinically for detecting children with a positive culture result: leukocyte esterase on a dipstick, white blood cell (WBC) count on manual microscopy with and without using a hemocytometer, automated WBC enumeration using flow cytometry, and automated WBC enumeration using digital imaging with particle recognition., Results: A total of 4188 children were included. Among febrile children, the sensitivity of the 2 most widely available modalities, the leukocyte esterase test and WBC enumeration using digital imaging, had sensitivity values of 84% (95% confidence interval, 0.80-0.87) and 75% (95% confidence interval, 0.66-0.83), respectively., Conclusions: Our findings suggest that for febrile children <36 months of age undergoing bladder catheterization for suspected UTI, pyuria will be absent in ∼20% of children who are eventually shown to have pure growth of a pathogen on a culture. This raises questions about the appropriateness of requiring pyuria for the diagnosis of UTIs., (Copyright © 2024 by the American Academy of Pediatrics.)

Importance: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care., Objective: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce., Evidence Review: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions., Findings: A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology., Conclusions and Relevance: The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients., (© 2024. The Author(s).)

Importance: Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% of children and 3% of adults who develop ESKD have FSGS, it remains uncertain whether the natural history differs in pediatric vs adult patients, and this uncertainty contributes to the exclusion of children and adolescents in clinical trials., Objective: To examine whether there are differences in the kidney health outcomes among children, adolescents, and adults with FSGS., Design, Setting, and Participants: This cohort study used pooled and parallel analyses, completed July 5, 2022, from 3 complimentary data sources: (1) Nephrotic Syndrome Rare Disease Clinical Research Network (NEPTUNE); (2) FSGS clinical trial (FSGS-CT); and (3) Kidney Research Network (KRN). NEPTUNE is a multicenter US/Canada cohort study; FSGS-CT is a multicenter US/Canada clinical trial; and KRN is a multicenter US electronic health record-based registry from academic and community nephrology practices. NEPTUNE included 166 patients with incident FSGS enrolled at first kidney biopsy; FSGS-CT included 132 patients with steroid-resistant FSGS randomized to cyclosporine vs dexamethasone with mycophenolate; and KRN included 184 patients with prevalent FSGS. Data were collected from November 2004 to October 2019 and analyzed from October 2020 to July 2022., Exposures: Age: children (age <13 years) vs adolescents (13-17 years) vs adults (≥18 years). Covariates of interest included sex, disease duration, APOL1 genotype, urine protein-to-creatinine ratio, estimated glomerular filtration rate (eGFR), edema, serum albumin, and immunosuppressive therapy., Main Outcomes and Measures: ESKD, composite outcome of ESKD or 40% decline in eGFR, and complete and/or partial remission of proteinuria., Results: The study included 127 (26%) children, 102 (21%) adolescents, and 253 (52%) adults, including 215 (45%) female participants and 138 (29%) who identified as Black, 98 (20%) who identified as Hispanic, and 275 (57%) who identified as White. Overall, the median time to ESKD was 11.9 years (IQR, 5.2-19.1 years). There was no difference in ESKD risk among children vs adults (hazard ratio [HR], 0.67; 95% CI, 0.43-1.03) or adolescents vs adults (HR, 0.85; 95% CI, 0.52-1.36). The median time to the composite end point was 5.7 years (IQR 1.6-15.2 years), with hazard ratio estimates for children vs adults of 1.12 (95% CI, 0.83-1.52) and adolescents vs adults of 1.06 (95% CI, 0.75-1.50)., Conclusions and Relevance: In this study, the association of FSGS with kidney survival and functional outcomes was comparable at all ages.

Chronic Kidney disease (CKD) is a major public health problem associated with increased health costs, morbidity, and mortality. There is a 30-fold higher mortality rate and severely impaired quality of life in children with chronic kidney disease (CKD), requiring dialysis or kidney transplant compared to the aged-match general population. The early diagnosis and treatment of pediatric CKD can reverse, delay or prevent progression to advanced kidney disease. It is worth noting that CKD with rapid progression, which carries a poor prognosis, is more common in African American children. Thus, the development of a universal pediatric CKD screening program for high-risk children can be vital for social equity. The disparity in prevalence and severity of CKD is likely due to a complex interaction between biological and nonbiological risk factors that influence the development and progression of CKD in children of African descent. For example, high-risk alleles in the gene encoding for apolipoprotein L1 (APOL1) have been recognized as the most important factor in the high incidence of some chronic kidney diseases in African Americans. In this review, we will focus on the trends in the incidence of pediatric CKD and management strategies aimed at enhancing health outcomes and reducing disease progression., (Copyright © 2022 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Introduction: Individuals with focal segmental glomerular sclerosis (FSGS) typically undergo kidney biopsy only once, which limits the ability to characterize kidney cell gene expression over time., Methods: We used single-cell RNA sequencing (scRNA-seq) to explore disease-related molecular signatures in urine cells from subjects with FSGS. We collected 17 urine samples from 12 FSGS subjects and captured these as 23 urine cell samples. The inflammatory signatures from renal epithelial and immune cells were evaluated in bulk gene expression data sets of FSGS and minimal change disease (MCD) (The Nephrotic Syndrome Study Network [NEPTUNE] study) and an immune single-cell data set from lupus nephritis (Accelerating Medicines Partnership)., Results: We identified immune cells, predominantly monocytes, and renal epithelial cells in the urine. Further analysis revealed 2 monocyte subtypes consistent with M1 and M2 monocytes. Shed podocytes in the urine had high expression of marker genes for epithelial-to-mesenchymal transition (EMT). We selected the 16 most highly expressed genes from urine immune cells and 10 most highly expressed EMT genes from urine podocytes as immune signatures and EMT signatures, respectively. Using kidney biopsy transcriptomic data from NEPTUNE, we found that urine cell immune signature and EMT signature genes were more highly expressed in FSGS biopsies compared with MCD biopsies., Conclusion: The identification of monocyte subsets and podocyte expression signatures in the urine samples of subjects with FSGS suggests that urine cell profiling might serve as a diagnostic and prognostic tool in nephrotic syndrome. Furthermore, this approach may aid in the development of novel biomarkers and identifying personalized therapies targeting particular molecular pathways in immune cells and podocytes., (© 2021 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Bariatric surgery improves markers of kidney health in severe obesity, yet it is unclear if kidney disease outcomes differ according to age at surgery. Therefore, we examined health effects of Roux-en-Y gastric bypass between 161 adolescents and 396 adults participating in two related but distinct studies. Primary outcomes were elevated urine albumin-to-creatinine ratio (UACR) of 30 mg/g or more and hyperfiltration (an estimated glomerular filtration rate of 135 ml/min/1.73m 2 or more). Analyses were stratified by the presence of pre-operative type 2 diabetes. Adolescents with pre-operative type 2 diabetes had a significantly increased prevalence of elevated UACR prior to surgery compared to adults (22.5 vs. 9.0%). Resolution of elevated UACR following surgery differed between adolescents and adults with type 2 diabetes, with adolescents experiencing a significantly earlier improvement following surgery. Adolescents without pre-operative type 2 diabetes demonstrated a significantly increased prevalence of UACR prior to surgery compared to adults (9.4 vs. 4.5%), with no improvement occurring in either group post-operatively. Adolescents with pre-operative type 2 diabetes had a significantly increased prevalence of hyperfiltration that remained throughout the study period, whereas hyperfiltration prevalence was similar among those without type 2 diabetes. Thus, adolescents with pre-operative type 2 diabetes experienced earlier attenuation of elevated UACR compared to adults with pre-operative type 2 diabetes in response to gastric bypass., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Pediatric-onset chronic kidney disease (CKD) is as relevant to adults as it is to children. Congenital anomalies of the kidney and urinary tract may have a significant impact on health from birth or during childhood or may not manifest until adulthood. Many acquired kidney diseases start to appear in late childhood and adolescence. The propensity for more rapid progression of CKD to end-stage kidney disease in adults of African ancestry, as well as disparities in access to kidney transplantation and allograft longevity, have been well documented for decades. Similar disparate patterns are seen in children, and we now know that there are a range of biological and nonbiological risk factors for the development and progression of CKD in people of African descent that are pertinent to CKD in children. In some cases, it is unclear whether there are effective potential interventions, whereas in other situations, there are opportunities to improve outcomes., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Limited health literacy has been associated with adverse outcomes in children. We evaluated this association in the setting of chronic kidney disease (CKD)., Methods: We assessed the parental health literacy of 367 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study, using the Short Test of Functional Health Literacy (STOFHLA). We evaluated the association between parental health literacy and CKD progression, defined as time to the composite event of renal replacement therapy (RRT, dialysis, or kidney transplant) or 50% decline in estimated glomerular filtration rate (eGFR)., Results: Median CKiD participant age was 9.5 years, 63% were male, and 59% non-Hispanic white. Median eGFR at baseline was 63 ml/min/1.73 m 2 , and median urine protein-to-creatinine ratio was 0.22. The median STOFHLA score was 98. Over a median follow-up of 3.7 years, the overall CKD progression rate was 2.8 per 100 person-years. After adjustment for demographic and clinical factors, the relative time to CKD progression was 28% longer per 1 SD increase in STOFHLA score (relative time, 95% CI, 1.28, 1.06-1.53)., Conclusions: In this cohort of children with CKD, higher parental health literacy was associated with a nearly 30% longer time to the composite CKD progression outcome.

Anhydramnios in the setting of severe malformations of the fetal kidney and urinary tract is associated with a high incidence of stillbirths and life-threatening complications, including severe pulmonary hypoplasia, umbilical cord compression, and perinatal asphyxia. To prevent such adverse outcomes, some centers in the United States and elsewhere are offering amniotic fluid restoration for women diagnosed with anhydramnios in the setting of fetal renal malformations. The procedures include infusions of amniotic fluid substitutes (normal saline), percutaneously or through an amnioport-an implanted system for serial or continuous infusion of normal saline to maintain the desired amniotic fluid volume. The procedures are intended to prevent pulmonary hypoplasia and allow the pregnancy to progress closer to term gestation, enabling postnatal renal management, including long-term dialysis and renal transplantation. However, these procedures have not been recommended as standard of care by the professional societies because there are many knowledge gaps, including few data on short-term and long-term renal outcomes. The available diagnostic methods do not provide reliable prognostic information, and the current maternal and fetal interventions have not been standardized. To address these unresolved issues and to propose a research agenda, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive and Kidney Diseases invited a panel of experts to a workshop in August 2016. This report provides a summary of that meeting.

Introduction: Technetium-99m dimercaptosuccinic acid (DMSA) renal scans are used in the diagnosis of renal scarring. In the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial that randomized 607 children, DMSA renal scans were used for evaluating the presence and the severity of renal scarring., Objective: The aim was to determine interobserver variability in reporting of DMSA renal scans in the RIVUR trial., Study Design: We compared DMSA renal scan reports for renal scarring and acute pyelonephritis from all non-reference local radiologists (ALRs) at study sites with adjudicated as well as non-adjudicated reports from two reference radiologists (RRs) of the RIVUR trial. Two-way comparisons of concordant and discrepant responses were analyzed using an unweighted kappa statistic between the ALR and the adjudicated RR interpretations. All analyses were performed using SAS v 9.4 (SAS institute 2015) and significance was determined at the 0.05 level., Results: Of the 2872 kidneys evaluated, adjudicated RR reports had 119 (4%) kidneys with renal scarring compared with 212 (7%) by the ALRs. For 79% kidneys the grading for scarring reported by ALRs was either upgraded (24%) or downgraded (55%) by RRs. For acute pyelonephritis (n = 2924), adjudicated RR reports had 85 (3%) kidneys with pyelonephritis compared with 151 (5%) by the ALRs. For 85% kidneys, the grading for pyelonephritis reported by the ALRs was either upgraded (28%) or downgraded (57%) by the RRs. A three-way comparison revealed that all three (RR1, RR2, and ALR) agreed over presence of renal scarring in 19% cases and two of the three agreed in 80% cases. The respective numbers for pyelonephritis were 13% and 84%. The agreement rate for all DMSA scan reports between the RRs and the ALRs was 93%., Discussion: The study revealed significant interobserver variability in the reporting of abnormal DMSA renal scans compared with the previously published studies. A noteworthy limitation was a lack of uniformity in local reporting of the scans., Conclusions: Our study highlights the need for optimizing the clinical yield of DMSA renal scans by more specific guidelines, particularly for standardized and uniform interpretation., (Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The conduct of clinical trials in small pediatric subspecialties such as pediatric nephrology is hampered by both clinical demands on the pediatric nephrologist and the small number of appropriate patients available for such studies. The American Society of Pediatric Nephrology Therapeutics Development Committee (TDC) was established to (1) identify the various stakeholders with interests and/or expertise related to clinical trials in children with kidney disease and (2) develop more effective partnerships among all parties regarding strategies for successful clinical trial development and execution. This article discusses the rationale, structure, and function of the TDC, the status of progress toward its goals, and the insights gained to date that may be useful for other subspecialties that face similar challenges.

In this review of 126 publications, we report that an overwhelming majority of adults born at preterm gestations remain healthy and well. However, a small, but a significant fraction of them remain at higher risk for neurological, personality and behavioural abnormalities, cardio-pulmonary functional limitations, systemic hypertension and metabolic syndrome compared to their term-born counterparts. The magnitude of increased risk differed across organ systems and varied across reports. The risks were proportional to the degree of prematurity at birth and seemed to occur more frequently among preterm infants born in the final two decades of the 20th century and later. These findings have considerable public health and clinical practice relevance., Conclusion: Preterm birth needs to be considered a chronic condition, with a slight increase in the risk for long-term morbidities among adults born preterm. Therefore, obtaining a history of gestational age and weight at birth should be a routine part of care for patients of all age groups., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Introduction: Voiding cystourethrogram (VCUG) provides a wealth of data on urinary tract function and anatomy, but few standards exist for reporting VCUG findings., Objective: We aimed to assess variability in VCUG reports and to test our hypothesis that VCUG reports from pediatric facilities and pediatric radiologists are more complete than those performed at other facilities or by non-pediatric radiologists., Study Design: We analyzed original VCUG reports from children enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial. A 23-item checklist was created and used to evaluate reporting of technical (e.g. catheter size), anatomic (e.g. vesicoureteral reflux (VUR) presence and grade, bladder shape), and functional information (e.g. bladder emptying). Radiologists were classified as pediatric or non-pediatric radiologists. Facilities were categorized as to whether they were a free-standing pediatric hospital (FSPH), a pediatric "hospital within a hospital" (PHWH), a non-pediatric hospital (NPH), or an outpatient radiology facility (ORF). Multivariate linear regression was used to analyze factors associated with the completeness of the VCUG reports (percent of items reported from the 23-item checklist)., Results: Six-hundred and two VCUGs were performed at 90 institutions. Of those, 76% were read by a pediatric radiologist, and 49% were performed at a FSPH (Table). On average, less than half of the 23 items in our standardized assessment tool were included in VCUG reports (mean 48%, SD 12). The completeness of reports varied by facility type: 51% complete at FSPH (SD 11), 50% at PHWH (SD 10), 36% at NPH (SD 11), and 43% at ORF (SD 8) (p < 0.0001). In multivariate analysis, VCUG reports generated at NPH or ORF had 8% fewer items included (95% CI 3.0-12.8, p < 0.01), and those generated at PHWH did not differ from those generated at FSPH. Reports read by a non-pediatric radiologist had 6% fewer items included (95% CI 3-9.7; p < 0.01) compared with those read by a pediatric radiologist., Discussion: There is substantial underreporting of findings in VCUG reports when assessing a widely represented sample of routine, community-generated reports using an idealized standard. Although VUR was often reported, other crucial anatomic and functional findings of the VCUG were consistently underreported across all facility types., Conclusion: Although pediatric radiologist and pediatric hospitals generated more complete VCUG reports compared with those having non-pediatric origins, the differences are small when considering the substantial underreporting of VCUG findings in general. This underscores the opportunities for improvement in reporting of VCUG findings., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Individuals of African ancestry harboring two variant alleles within apolipoprotein L1 ( APOL1 ) are classified with a high-risk (HR) genotype. Adults with an HR genotype have increased risk of focal segmental glomerulosclerosis and chronic kidney disease compared with those with a low-risk (LR) genotype (0 or 1 variants). The role of APOL1 risk genotypes in children with glomerular disease is less well known., Methods: This study characterized 104 African-American children with a glomerular disease by APOL1 genotype in two cohorts: the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE)., Results: Among these subjects, 46% had an HR genotype with a similar age at cohort enrollment. For APOL1 HR children, the median age of disease onset was older (CKiD: 4.5 versus 11.5 years for LR versus HR; NEPTUNE: 11 versus 14 years for LR versus HR, respectively) and preterm birth was more common [CKiD: 27 versus 4%; NEPTUNE: 26 versus 12%; combined odds ratio 4.6 (95% confidence interval: 1.4, 15.5)]. Within studies, HR children had lower initial estimated glomerular filtration rate (eGFR) (CKiD: 53 versus 69 mL/min/1.73 m 2 ; NEPTUNE: 74 versus 94 mL/min/1.73 m 2 ). Longitudinal eGFR decline was faster among HR children versus LR (CKiD: -18 versus -8% per year; NEPTUNE: -13 versus -3% per year)., Conclusions: Children with an HR genotype in CKiD and NEPTUNE seem to have a more aggressive form of glomerular disease, in part due to a higher prevalence of focal segmental glomerulosclerosis. These consistent findings across independent cohorts suggest a common natural history for children with APOL1 -associated glomerular disease. Further study is needed to determine the generalizability of these findings., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Introduction: Voiding cystourethrography (VCUG) is the modality of choice to diagnose vesicoureteral reflux (VUR). Although grading of VUR is essential for prognosis and clinical decision-making, the inter-observer reliability for grading has been shown to vary substantially. The Randomized Intervention for Children with VesicoUreteral Reflux (RIVUR) trial provides a large cohort of children with VUR to better understand the reliability of VCUG findings., Objective: To determine the inter-observer consistency of the grade of VUR and other VCUG findings in a large cohort of children with VUR., Study Design: The RIVUR trial is a randomized controlled trial of antimicrobial prophylaxis in children with VUR diagnosed after UTI. Each enrollment VCUG was read by a local clinical (i.e. non-reference) radiologist, and independently by two blinded RIVUR reference radiologists. Reference radiologists' disagreements were adjudicated for trial purposes. The grade of VUR and other VCUG findings were extracted from the local clinical radiologist's report. The unit of analysis included individual ureters and individual participants. We compared the three interpretations for grading of VUR and other VCUG findings to determine the inter-observer reliability., Results: Six-hundred and two non-reference radiology reports from 90 institutions were reviewed and yielded the grade of VUR for 560 left and 524 right ureters. All three radiologists agreed on VUR grade in only 59% of ureters; two of three agreed on 39% of ureters; and all three disagreed on 2% of ureters (Table). Agreement was better (≥92%) for other VCUG findings (e.g. bladder shape "normal"). The non-reference radiologists' grade of VUR differed from the reference radiologists' adjudicated grade by exactly one grade level in 19% of ureters, and by two or more grade levels in 2.2% of ureters. When the participant was the unit of analysis, all three radiologists agreed on the grade of VUR in both ureters in just 43% of cases., Discussion: Our study shows considerable and clinically relevant variability in grading VUR by VCUG. This variability was consistent when comparing non-reference to the adjudicated reference radiologists' assessment and the reference radiologists to each other. This study was limited to children with a history of UTI and grade I-IV VUR and may not be generalizable to all children who have a VCUG., Conclusion: The considerable inter-observer variability in VUR grading has both research and clinical implications, as study design, risk stratification, and clinical decision-making rely heavily on grades of VUR., (Copyright © 2016 Journal of Pediatric Urology Company. All rights reserved.)

Purpose: African American (AA) adults with chronic kidney disease (CKD) have a faster progression to end-stage renal disease and are less likely to receive a kidney transplant. It is unclear whether AA children experience renal replacement therapy (RRT) for end-stage renal disease sooner than non-AA children after accounting for socioeconomic status (SES)., Methods: Among children with nonglomerular CKD in the Chronic Kidney Disease in Children study, we investigated time to RRT (i.e., first dialysis or transplant) after CKD onset using parametric survival models and accounted for SES differences by inverse probability weights., Results: Of 110 AA and 493 non-AA children (median age = 10 years), AA children had shorter time to first RRT: median time was 3.2 years earlier than non-AA children (95% CI: -6.1, -0.3). When accounting for SES, this difference was diminished and nonsignificant (-1.6 years; 95% CI: -4.6, +1.5), and its directionality was consistent with faster glomerular filtration rate decline among AA children (-6.2% vs. -4.4% per year, P = .098). When RRT was deconstructed into dialysis or transplant, the time to dialysis was 37.5% shorter for AA children and 53.7% longer for transplant. These inferences were confirmed by the frequency and timing of transplant after initiating dialysis., Conclusions: Racial differences in time to RRT were almost fully accounted for by SES, and the remaining difference was congruent with a faster glomerular filtration rate decline among AA children. Access to transplant occurred later, yet times to dialysis were shorter among AA children even when accounting for SES which may be due to a lack of organ availability., Competing Interests: Statement of competing financial interests. All the authors declared no competing interests., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We aimed to determine which children are prone to non-Escherichia coli urinary tract infection (UTIs). We included 769 children with UTI. We found that circumcised males, Hispanic children, children without fever and children with grades 3 and 4 vesicoureteral reflux were more likely to have a UTI caused by organisms other than E. coli. This information may guide clinicians in their choice of antimicrobial therapy.

Background: No studies have examined whether use of sedation during a Tc-99 m dimercaptosuccinic acid (DMSA) renal scan reduces patient discomfort., Objective: To compare discomfort level during a DMSA scan to the discomfort level during other frequently performed uroradiologic tests, and to determine whether use of sedation during a DMSA scan modifies the level of discomfort., Materials and Methods: We examined the discomfort level in 798 children enrolled in the Randomized Intervention for children with Vesicoureteral Reflux (RIVUR) and Careful Urinary Tract Infection Evaluation (CUTIE) studies by asking parents to rate their child's discomfort level with each procedure on a scale from 0 to 10. We compared discomfort during the DMSA scan and the DMSA image quality between centers in which sedation was used >90% of the time (sedation centers), centers in which sedation was used <10% of the time (non-sedation centers), and centers in which sedation was used on a case-by-case basis (selective centers)., Results: Mean discomfort level was highest for voiding cystourethrogram (6.4), followed by DMSA (4.0), followed by ultrasound (2.4; P<0.0001). Mean discomfort level during the DMSA scan was significantly higher at non-sedation centers than at selective centers (P<0.001). No difference was apparent in discomfort level during the DMSA scan between sedation centers and selective centers (P=0.12), or between the sedation centers and non-sedation centers (P=0.80). There were no differences in the proportion with uninterpretable DMSA scans according to sedation use., Conclusion: Selective use of sedation in children 12-36 months of age can reduce the discomfort level experienced during a DMSA scan., Competing Interests: Compliance with ethical standards: Conflicts of interest: None

Importance: Existing data regarding the association between delayed initiation of antimicrobial therapy and the development of renal scarring are inconsistent., Objective: To determine whether delay in the initiation of antimicrobial therapy for febrile urinary tract infections (UTIs) is associated with the occurrence and severity of renal scarring., Design, Setting, and Participants: Retrospective cohort study that combined data from 2 previously conducted longitudinal studies (the Randomized Intervention for Children With Vesicoureteral Reflux trial and the Careful Urinary Tract Infection Evaluation Study). Children younger than 6 years with a first or second UTI were followed up for 2 years., Exposure: Duration of the child's fever prior to initiation of antimicrobial therapy for the index UTI., Main Outcomes and Measures: New renal scarring defined as the presence of photopenia plus contour change on a late dimercaptosuccinic acid renal scan (obtained at study exit) that was not present on the baseline scan., Results: Of the 482 children included in the analysis, 434 were female (90%), 375 were white (78%), and 375 had vesicoureteral reflux (78%). The median age was 11 months. A total of 35 children (7.2%) developed new renal scarring. Delay in the initiation of antimicrobial therapy was associated with renal scarring; the median (25th, 75th percentiles) duration of fever prior to initiation of antibiotic therapy in those with and without renal scarring was 72 (30, 120) and 48 (24, 72) hours, respectively (P = .003). Older age (OR, 1.03; 95% CI, 1.01-1.05), Hispanic ethnicity (OR, 5.24; 95% CI, 2.15-12.77), recurrent urinary tract infections (OR, 0.97; 95% CI, 0.27-3.45), and bladder and bowel dysfunction (OR, 6.44; 95% CI, 2.89-14.38) were also associated with new renal scarring. Delay in the initiation of antimicrobial therapy remained significantly associated with renal scarring even after adjusting for these variables., Conclusions and Relevance: Delay in treatment of febrile UTIs and permanent renal scarring are associated. In febrile children, clinicians should not delay testing for UTI.

Background: Children with chronic kidney disease (CKD) may have impaired caloric intake through a variety of mechanisms, with decreased appetite as a putative contributor. In adult CKD, decreased appetite has been associated with poor clinical outcomes. There is limited information about this relationship in pediatric CKD., Methods: A total of 879 participants of the Chronic Kidney Disease in Children (CKiD) study were studied. Self-reported appetite was assessed annually and categorized as very good, good, fair, or poor/very poor. The relationship between appetite and iohexol or estimated glomerular filtration rate (ieGFR), annual changes in anthropometrics z-scores, hospitalizations, emergency room visits, and quality of life were assessed., Results: An ieGFR < 30 ml/min per 1.73 m(2) was associated with a 4.46 greater odds (95 % confidence interval: 2.80, 7.09) of having a worse appetite than those with ieGFR >90. Appetite did not predict changes in height, weight, or BMI z-scores. Patients not reporting a very good appetite had more hospitalizations over the next year than those with a very good appetite. Worse appetite was significantly associated with lower parental and patient reported quality of life., Conclusions: Self-reported appetite in children with CKD worsens with lower ieGFR and is correlated with clinical outcomes, including hospitalizations and quality of life.

Background: The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial found that recurrent urinary tract infections (rUTI) with resistant organisms were more common in the trimethoprim-sulfamethoxazole prophylaxis (TSP) arm. We describe factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) resistance of rUTIs in RIVUR., Methods: Children aged 2 to 71 months with first or second UTI (index UTI) and grade I to IV vesicoureteral reflux (VUR) were randomized to TSP or placebo and followed for 2 years. Factors associated with TMP-SMX-resistant rUTI were evaluated., Results: Among 571 included children, 48% were <12 months old, 43% had grade II VUR, and 38% had grade III VUR. Recurrent UTI occurred in 34 of 278 children receiving TSP versus 67 of 293 children receiving placebo. Among those with rUTI, 76% (26/34) of subjects receiving TSP had TMP-SMX-resistant organisms versus 28% (19/67) of subjects receiving placebo (P < .001). The proportion of TMP-SMX-resistant rUTI decreased over time: in the TSP arm, 96% were resistant during the initial 6 months versus 38% resistant during the final 6 months; corresponding proportions for the placebo arm were 32% and 11%. Among children receiving TSP, 7 (13%) of 55 with TMP-SMX-resistant index UTI had rUTI, whereas 27 (12%) of 223 with TMP-SMX-susceptible index UTI had rUTI (adjusted hazard ratio 1.38, 95% confidence interval 0.54-3.56). Corresponding proportions in placebo arm were 17 (26%) of 65 and 50 (22%) of 228 (adjusted hazard ratio 1.33, 95% confidence interval 0.74-2.38)., Conclusions: Although TMP-SMX resistance is more common among children treated with TSP versus placebo, resistance decreased over time. Among children treated with TSP, there was no significant difference in UTI recurrence between those with TMP-SMX-resistant index UTI versus TMP-SMX-susceptible UTI., (Copyright © 2016 by the American Academy of Pediatrics.)

Low birth weight (LBW) and intrauterine growth restriction are major contributors to the global burden of non-communicable diseases. A Norwegian registry study has confirmed that LBW is associated with an increased risk of developing end-stage renal disease by 40 years of age, which could not be explained by familial factors.

Objective: To determine which children with urinary tract infection are likely to have pathogens resistant to narrow-spectrum antimicrobials., Study Design: Children, 2-71 months of age (n = 769) enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux or Careful Urinary Tract Infection Evaluation studies were included. We used logistic regression models to test the associations between demographic and clinical characteristics and resistance to narrow-spectrum antimicrobials., Results: Of the included patients, 91% were female and 76% had vesicoureteral reflux. The risk of resistance to narrow-spectrum antibiotics in uncircumcised males was approximately 3 times that of females (OR 3.1; 95% CI 1.4-6.7); in children with bladder bowel dysfunction, the risk was 2 times that of children with normal function (OR 2.2; 95% CI 1.2-4.1). Children who had received 1 course of antibiotics during the past 6 months also had higher odds of harboring resistant organisms (OR 1.6; 95% CI 1.1-2.3). Hispanic children had higher odds of harboring pathogens resistant to some narrow-spectrum antimicrobials., Conclusions: Uncircumcised males, Hispanic children, children with bladder bowel dysfunction, and children who received 1 course of antibiotics in the past 6 months were more likely to have a urinary tract infection caused by pathogens resistant to 1 or more narrow-spectrum antimicrobials., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background and Objectives: The main objectives of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial were to evaluate the role of antimicrobial prophylaxis in the prevention of recurrent urinary tract infection (UTI) and renal scarring in children with vesicoureteral reflux (VUR). We present a comprehensive evaluation of renal scarring outcomes in RIVUR trial participants., Design, Setting, Participants, & Measurements: This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2-71 months with grade 1-4 VUR diagnosed after a first or second febrile or symptomatic UTI. Study participants received trimethoprim-sulfamethoxazole or placebo and were followed for 2 years. Renal scarring was evaluated by baseline and follow-up (99m)technetium dimercaptosuccinic acid (DMSA) renal scans that were reviewed independently by two blinded reference radiologists., Results: At the end of the study, 58 (10%) of 599 children and 63 (5%) of 1197 renal units had renal scarring. New renal scarring did not differ between the prophylaxis and placebo groups (6% versus 7%, respectively). Children with renal scarring were significantly older (median age, 26 versus 11 months; P=0.01), had a second UTI before enrollment (odds ratio [OR], 2.85; 95% confidence interval [95% CI], 1.38 to 5.92), were more likely to be Hispanic (OR, 2.22; 95% CI, 1.13 to 4.34), and had higher grades of VUR (OR, 2.79; 95% CI, 1.56 to 5.0). The proportion of new scars in renal units with grade 4 VUR was significantly higher than in units with no VUR (OR, 24.2; 95% CI, 6.4 to 91.2)., Conclusions: Significantly more renal scarring was seen in relatively older children and in those with a second episode of febrile or symptomatic UTI before randomization. Preexisting and new renal scars occurred significantly more in renal units with grade 4 VUR than in those with low-grade or no VUR. Antimicrobial prophylaxis did not decrease the risk of renal scarring., (Copyright © 2016 by the American Society of Nephrology.)

Background: Little generalizable information is available on the outcomes of children diagnosed with bladder and bowel dysfunction (BBD) after a urinary tract infection (UTI). Our objectives were to describe the clinical characteristics of children with BBD and to examine the effects of BBD on patient outcomes in children with and without vesicoureteral reflux (VUR)., Methods: We combined data from 2 longitudinal studies (Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation) in which children <6 years of age with a first or second UTI were followed for 2 years. We compared outcomes for children with and without BBD, children with and without VUR, and children with VUR randomly assigned to prophylaxis or placebo. The outcomes examined were incidence of recurrent UTIs, renal scarring, surgical intervention, resolution of VUR, and treatment failure., Results: BBD was present at baseline in 54% of the 181 toilet-trained children included; 94% of children with BBD reported daytime wetting, withholding maneuvers, or constipation. In children not on antimicrobial prophylaxis, 51% of those with both BBD and VUR experienced recurrent UTIs, compared with 20% of those with VUR alone, 35% with BBD alone, and 32% with neither BBD nor VUR. BBD was not associated with any of the other outcomes investigated., Conclusions: Among toilet-trained children, those with both BBD and VUR are at higher risk of developing recurrent UTIs than children with isolated VUR or children with isolated BBD and, accordingly, exhibit the greatest benefit from antimicrobial prophylaxis., (Copyright © 2016 by the American Academy of Pediatrics.)

Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk genotypes are common in African-American subjects with primary FSGS and may also be present in individuals who do not self-identify as African American. APOL1 risk status is associated with lower kidney function, more glomerulosclerosis and interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk genotype did not influence proteinuria responses to cyclosporin or mycophenolate mofetil/dexamethasone., (Copyright © 2015 by the American Society of Nephrology.)