Nephrocalcinosis in Neonates.

Nephrocalcinosis occurs in as many as 40% of preterm neonates. Many causes and contributors predispose neonates to develop nephrocalcinosis, including metabolic, genetic, and iatrogenic factors. Because nephrocalcinosis can be a manifestation of an underlying genetic disorder, neonates with nephrocalcinosis must undergo an evaluation to identify and address contributors, to prevent further renal calcium deposition that can potentially lead to renal dysfunction. In this article, we review the epidemiology, pathogenesis, diagnosis, and evaluation of nephrocalcinosis in neonates. We also summarize the natural history of nephrocalcinosis of prematurity as well as the management of this condition.

Persistent Increase in Serum Ferritin Levels despite Converting to Permanent Vascular Access in Pediatric Hemodialysis Patients: Pediatric Nephrology Research Consortium Study.

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL (p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year (p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology (p = 0.035), being from a center that enrolled >10 cases (p = 0.049) and baseline serum ferritin level (p = 0.017). Increasing serum ferritin after conversion to PVA is concerning. This increase is not associated with serum hematocrit trends. Future studies should investigate the correlation of serum transferrin saturation and ferritin levels in pediatric HD patients.

Educational Relative Value Units as a Measure of Academic Productivity: A Systematic Review.

INTRODUCTION: Academic Health Centers (AHCs) have complex, often competing missions. Many have developed mission-based management (MBM) systems to support their clinical and non-clinical missions. There are limited data on MBM use for their educational missions. Our scoping review explored how AHCs employed such systems.  Materials and methods: Arksey and O'Malley's six-stage framework guided our review. Based on pre-defined criteria, English language articles from PubMed, EMBASE, SCOPUS, and the Healthcare Administration Database published between 2010 and 2020 were loaded into a reference manager. The search included all health professions education schools. Articles were excluded if they were review articles, commentaries, or clearly did not involve funding for education. From the final list of selected articles, data were extracted using a data extraction sheet we developed. Two researchers reviewed each article again to ensure extracted data were reported consistently and with sufficient detail.  Results: Of the 1729 manuscripts identified, 35 met inclusion criteria. Sixteen (46%) contained data in some form but did not have a formal methods section describing the specific approach to data collection and analysis. Moreover, there was marked variability in how educational effort was quantified, what counted as educational effort (educational scholarship versus teaching) and the impacts of such quantification (departmental funding versus individual faculty incentives). None of the studies reported on the impact on faculty promotion. Faculty satisfaction with the system was reported in seven studies (20%) and was generally positive. CONCLUSIONS: A systematic description of how systems were developed to support the educational mission was lacking. Clear goals, methods of development, uniform data on educational productivity and quality, and program evaluation were not defined by most articles. This lack of process clarity presents a challenge, but more importantly an opportunity for academic health centers to unify efforts and continue to further their educational mission.

Tidal continuous cycling peritoneal dialysis in children.

About 10% of all home peritoneal dialysis regimens in children with chronic kidney disease stage 5 are reported to involve some form of a tidal peritoneal dialysis (TPD) prescription. Despite this, there remain several gaps in how pediatric nephrologists approach the use of TPD. This stems from a combination of factors such as the confusing technical terminology pertaining to TPD, seemingly conflicting data on the risks, benefits, and indications for TPD, and lastly, limited published guidelines on the practical aspects of how to write a TPD prescription, based on the indication, in children. Our educational review, using evidence-based data, attempts to bridge this gap and provide an easy-to-use guide on the key practical aspects of TPD in children.

Hypogammaglobulinemia in pediatric kidney transplant recipients.

Infections remain the most common cause of hospitalization after kidney transplantation, contributing to significant post-transplant morbidity and mortality. There is a growing body of literature that suggests that immunoglobulins may have a significant protective role against post-transplant infections, although the literature remains sparse, inconsistent, and not well publicized among pediatric nephrologists. Of great concern are data indicating a high prevalence of immunoglobulin abnormalities following transplantation and a possible link between these abnormalities and poorer outcomes. Our educational review focuses on the epidemiology and risk factors for the development of immunoglobulin abnormalities after kidney transplantation, the outcomes in patients with low immunoglobulin levels, and studies evaluating possible interventions to correct these immunoglobulin abnormalities.

Urologic Considerations in Pediatric Chronic Kidney Disease.

Common causes of pediatric ESRD are distinct from those seen in the adult population. In the pediatric population, the most common are congenital anomalies of the kidney and urinary tract (CAKUT), affecting approximately 30% of children with CKD. These structural anomalies often require coordinated care with the pediatric urology team to address voiding issues, bladder involvement, and the potential need for surgical intervention. For pediatric nephrologists and urologists, common CAKUT that are encountered include antenatal hydronephrosis, obstructive uropathies (eg, posterior urethral valves), and vesicoureteral reflux. As more pediatric patients with CAKUT, CKD, and ESRD transition to adult care, it is important for receiving adult nephrologists to understand the clinical presentation, natural history, and prognosis for these diagnoses. This review outlines the diagnosis and potential interventions for these conditions, including strategies to address bladder dysfunction that is often seen in children with CAKUT. A discussion of these management decisions (including surgical intervention) for CAKUT, which are quite common to pediatric nephrology and urology practices, may provide unique learning opportunities for adult nephrologists who lack familiarity with these pediatric conditions.

Case-control study exploring the short-term association of bronchiolitis with high blood pressure and hypertension in hospitalized children.

BACKGROUND: Unlike in adults, there are limited pediatric data exploring the association between acute respiratory illnesses and blood pressure abnormalities. The aim of our study was to explore the association of bronchiolitis, a common respiratory illness, with elevated blood pressure in hospitalized children. METHODS: In this single center retrospective case-control study, we evaluated the association between bronchiolitis and elevated blood pressure and hypertension in hospitalized children, compared to a control group admitted with nonrespiratory conditions, using multivariate regression analyses. Standard published normative data on pediatric blood pressure were used to classify children in various blood pressure categories. RESULTS: A high prevalence of elevated blood pressure (16%) and hypertension (60%) was noted among children with bronchiolitis; this was not statistically different from the control group (18% for elevated blood pressure; 57% for hypertension; P-values, 0.71 and 0.53, respectively). On multivariate regression analyses, only length of stay was associated with hypertension. No patient with blood pressure abnormalities received antihypertensives nor were any nephrology consults documented. CONCLUSIONS: A high prevalence of blood pressure abnormalities, without documentation of their recognition, was noted in hospitalized children regardless of diagnosis, pointing to the need for more data on outcomes-driven significance of pediatric inpatient blood pressure measurements.

Outcomes of living unrelated donor kidney transplants in children: An Organ Procurement and Transplant Network database analysis.

BACKGROUND: There are conflicting data on long-term outcomes of pediatric LURD renal Txs compared to Txs of kidneys from other donor sources. METHODS: An analysis of the OPTN database was conducted in children (<18 years) who had received their 1st kidney-only Tx between January 1, 2000, and September 30, 2021. The primary outcome measure was time to graft failure or death. Cox event history regression model for time to primary outcome, categorized by donor source and adjusting for confounders was performed. RESULTS: Of the 12 089 subjects, 327 (2.7%) received kidneys from LURDs, 4349 (36%) from LRDs and 7413 (61%) from DD. One year graft failure rate was 3.56%. On regression analyses, compared to LRD kidney recipients, LURD recipients had comparable graft survival (graft failure AHR 1.15, 95th percentile confidence interval 0.87-1.51; p .31) and DD recipients had lower graft survival (graft failure hazard ratio 1.26, 95th percentile confidence interval 1.10-1.43; p < .001). When using living unrelated kidney recipients as the reference group, DD kidney recipients had comparable graft survival, with a wide confidence interval (hazard ratio for graft failure 1.09; 0.83-1.43, p .53). CONCLUSIONS: Pediatric LURD kidney recipients have comparable graft survival to LRD kidney recipients; DD kidney recipients had the poorest survival. Our study, the largest to date, should encourage centers to embrace non-commercial living-unrelated transplantation as a viable option for children, preferable to DD kidneys.

Exploring how national educational organizations can promote educational research amongst members: a survey-based study.

BACKGROUND: Engagement of academic faculty in research remains low. While barriers to research have been explored, there are no data on how national organizations can help overcome these barriers. Our study explored faculty satisfaction and motivational drivers for engagement with research opportunities offered by the Council on Medical Student Education in Pediatrics (COMSEP), an organization of pediatric medical educators, and characterize strategies perceived by faculty to promote the use of these opportunities. METHODS: In 2021, 5 survey questions were administered to faculty members of COMSEP to explore satisfaction with COMSEP's research offerings, the perceived value of educational research, and the facilitators, barriers and potential opportunities for COMSEP to promote research. Clark's Commitment and Necessary Effort model on motivation served as the theoretical framework for our study, which explores motivation, self-efficacy and contextual factors influencing an individual's pursuit of goals. Chi-square analysis and Wilcoxon Signed Ranks Test were used to compare categorical and scaled variables among groups who did and did not avail of COMSEP's research offerings. RESULTS: 90 (25%) of 360 recipients responded. 61% expressed satisfaction with COMSEP's research offerings. 68% indicated research was an expectation of their academic appointment, that education was their primary research focus (74%) and that they did not have other research opportunities that met their needs (58%). Of respondents, 75.7% of females had submitted a proposal compared to 60% of non-responders who were females. The comparison by gender was not statistically significant. Exploration by academic rank revealed that 35% of instructor/assistant professors had submitted a proposal compared to 65% of associate professors/professors (p =.05). Barriers leading to non-submission to any of the offerings included having too much other work, lack of enjoyment in writing and inability to find mentors. Respondents endorsed the importance of several strategies to promote engagement in research-skill building opportunities, personalized consultations and increased funding. CONCLUSIONS: Faculty educators value the importance of educational research and recognize that research opportunities offered by COMSEP address an unmet need, but express ambivalence in the enjoyment of writing (reflecting their mood), and endorse structural barriers, that are amenable to change, affecting their personal agency.

Diabetic kidney disease in children and adolescents: an update.

Diabetic kidney disease (DKD), previously encountered predominantly in adult patients, is rapidly gaining center stage as a childhood morbidity and one that pediatric nephrologists are likely to encounter with increasing frequency. This is in large part due to the obesity epidemic and the consequent rise in type 2 diabetes in children and adolescents, as well as the more aggressive diabetes phenotype in today's youth with more rapid ß-cell decline and faster development and progression of diabetes-related complications along with lower responsiveness to the treatments used in adults. DKD, an end-organ complication of diabetes, is at the very least a marker of, and more likely a predisposing factor for, the development of adverse cardiovascular outcomes and premature mortality in children with diabetes. On an optimistic note, several new therapeutic approaches are now available for the management of diabetes in adults, such as GLP1 receptor agonists, SGLT2 inhibitors, and DPP4 inhibitors, that have also been shown to have a favorable impact on cardiorenal outcomes. Also promising is the success of very low-energy diets in inducing remission of diabetes in adults. However, the addition of these pharmacological and dietary approaches to the management toolbox of diabetes and DKD in children and adolescents awaits thorough assessment of their safety and efficacy in this population. This review outlines the scope of diabetes and DKD, and new developments that may favorably impact the management of children and young adults with diabetes and DKD.

Uncovering a Long-term Graft Survival Advantage Afforded by Infant Renal Transplants-An Organ Procurement and Transplantation Network Database Analysis.

BACKGROUND: Renal transplants (Tx) are performed infrequently in infants, due to concerns related to poor outcomes. The aim of our study was to compare graft failure rates in infant (<1 y) renal Tx recipients compared with older children. METHODS: Retrospective cohort study of pediatric renal Tx recipients from 2000 to 2015, using the Organ Procurement and Transplant Network database. A log-linear event history regression model for time to graft failure, adjusting for age group and important confounders, was used to estimate post-Tx graft failure probabilities. RESULTS: In 2696 Tx followed for a median of 6.1 y, 704 failures were observed. Significant predictors of graft failure were year of Tx (for each year after 2000, rates were 8.6% lower), Black race-ethnicity (63% higher compared with Whites), and number of HLA matches. For infants (n = 27), estimated graft failure percentage (95% confidence interval) within the first 1-, 2-, and 5-y post-Tx were 10.4 (0.1-21.1), 11.9 (1.2-22.6), and 16.4 (4.9-27.9). For the 1- to 11-y-olds (n = 1429), these were 3.8 (3.0-4.6), 6.3 (5.4-7.3), and 13.6 (12.2-15.0), respectively, and for the 12+ y olds (n = 1240), they were 3.8 (3.1-4.5), 8.1 (7.2-9.0), and 19.9 (18.1-21.7), respectively (P < 0.001 for 5-y graft failure rate across age groups). CONCLUSIONS: Infant renal Tx recipients experience a higher graft failure rate in the first year, compared with older cohorts, but over longer intervals, cumulative failure rates are comparable or even lower. To minimize early graft losses such Tx should be performed in experienced centers.

Intravenous cyclophosphamide induces remission in children with difficult to treat steroid resistant nephrotic syndrome from minimal change disease.

BACKGROUND: Steroid resistant nephrotic syndrome (SRNS), while uncommon in children, is associated with significant morbidity. Calcineurin inhibitors (CNIs) remain the first line recommended therapy for children with non-genetic forms of SRNS, but some children fail to respond to them. Intravenous (IV) cyclophosphamide (CTX) has been shown to be effective in Asian-Indian children with difficult to treat SRNS (SRNS-DTT). Our study evaluated the outcome of IV CTX treatment in North American children with SRNS-DTT. METHODS: Retrospective review of the medical records of children with SRNS-DTT treated with IV CTX from January 2000 to July 2019 at our center. Data abstracted included demographics, histopathology on renal biopsy, prior and concomitant use of other immunosuppressive agents and serial clinical/laboratory data. Primary outcome measure was attainment of complete remission (CR). RESULTS: Eight children with SRNS-DTT received monthly doses (median 6; range 4-6) of IV CTX. Four (50%) went into CR, 1 achieved partial remission and 3 did not respond. Three of the 4 responders had minimal change disease (MCD). Excluding the 1 child who responded after the 4th infusion, the median time to CR was 6.5 (range 0.5-8) months after completion of IV CTX infusions. Three remain in CR at a median of 8.5 years (range: 3.7-10.5 years) after completion of CTX; one child relapsed and became steroid-dependent. No infections or life-threatening complications related to IV CTX were observed. CONCLUSIONS: IV CXT can induce long term remission in North-American children with MCD who have SRNS-DTT.

Conversion to permanent vascular access is associated with improved markers of hemodialysis efficacy in children: Pediatric nephrology research consortium study.

BACKGROUND AND OBJECTIVES: Arteriovenous fistulae (AVF) and grafts (AVG) are preferred permanent vascular access (PVA) for chronic hemodialysis (HD) patients. Our objective was to examine the change in markers of HD efficacy after successful establishment of a PVA among children who started HD with a tunneled cuffed catheter (TCC). MATERIALS AND METHODS: Retrospective chart reviews were completed on patients from 20 pediatric dialysis centers. All patients used TCC prior to AVF/AVG, and each patient acted as his/her own control. Data on markers of HD efficacy (single-pool Kt/V, urea reduction ratio (URR), serum albumin and hematocrit (Hct)) were collected at the creation of AVF/AVG and for 2 years thereafter. Statistical methods included hypothesis testing and statistical modeling after adjusting for relevant demographic variables. RESULTS: First PVA was created in 98 individual children: 87 (89%) were AVF and 11 (11%) were AVG. The mean TCC vintage prior to AVF/AVG was 10.4 ± 17.3 months. At 1-year follow-up, Kt/V improved by 0.15 ± 0.06 (p = 0.02) and URR improved by 4.54 ± 1.17% (p < 0.0001). Furthermore, PVA was associated with improved serum albumin by 0.31 ± 0.07 g/dL (p < 0.0001) and Hct by 2.80 ± 0.65% (p < 0.0001) at 1 year. These HD efficacy markers remained statistically significant at 2nd-year follow-up. These observations were further supported by the adjusted models. Conversion to AVF was associated with statistically significant improvement in all four markers of HD efficacy at 1-year follow-up. This trend was not demonstrated for subjects who were converted to AVG. CONCLUSION: Switching to PVA was associated with improved markers of HD efficacy, single-pool Kt/V, URR, serum albumin, and Hct. This improvement was mostly demonstrated at 1 year and maintained for the 2nd year. The potential differential impact of the type of PVA on the trajectory of markers of HD efficacy should be further investigated.

Entrustable Professional Activity-Based Assessments in Undergraduate Medical Education: A Survey of Pediatric Educators.

OBJECTIVE: To explore the use of entrustable professional activities (EPAs) in undergraduate medical education (UME), characterization of EPAs by pediatric educators, and opportunities and challenges with an EPA framework. METHODS: In 2020, 9 survey questions were administered to members of the Council on Medical Student Education in Pediatrics, a national pediatric UME group. Clark's Commitment and Necessary Effort model on motivation served as the theoretical framework for our study. Quantitative and qualitative data were analyzed using descriptive statistics and conventional content analysis, respectively. RESULTS: One hundred and sixty-seven (31%) of 479 recipients, representing 75% of accredited schools responded. Eigty-three percent agreed that they understood what EPAs were, yet a minority reported using EPAs. Eighty-five percent of EPA users expressed satisfaction with EPAs in providing a shared framework and an opportunity to track student competence; dissatisfaction was expressed toward faculty resource needs. Among nonusers, barriers hindering implementation included faculty development challenges and faculty time. Qualitative analyses revealed a rich understanding of EPAs: that they offer a framework to measure learner competence by assessing performance in workplace-based tasks that can be used for entrustment decisions and for program evaluation. CONCLUSIONS: Although most pediatric UME educators report understanding EPAs (contributing to self-efficacy) and recognize their benefits (value), a minority report actually using EPAs. EPAs, while providing a valuable framework, pose challenges from contextual factors affecting personal agency, which could affect educator commitment in implementation. For more widespread adoption of the EPAs, efforts should focus on minimizing these perceived barriers.

Establishing an educational value unit to promote teaching in an academic unit.

Background: In academic health centers, education remains an incompletely supported and funded mandate. In an attempt to promote education and better support educational endeavors of faculty, some academic health centers and departments have conceived of a metric, the educational value unit (eVU), to begin to "quantify" teaching. What goes into this metric, its intended goals and the logistics of its implementation vary considerably among centers. Lessons Learned: This practical advice paper highlights the various lessons learned from a review of the limited published literature on eVU systems supplemented with our personal experience in implementing a successful eVU system in the Department of Pediatrics at our institution, to help guide others who may be interested in doing that same. Even in limited-resource settings, our hope is that these lessons can serve as a guide on how to better quantify and reward teaching, whether through monetary or nonfiscal incentives and recognition.

Effect of a patient-led educational session on pre-clerkship students' learning of professional values and on their professional development.

BACKGROUND: While there are several curricula using patients as educators, little has been published on how they affect student learning and professional development. OBJECTIVE: To explore what 1st year medical students learn about professional values from a patient-led educational experience and how it affects their professional development. DESIGN: We piloted a pediatric patient and family-led educational session during the molecular medicine course, with the goal of sharing the experience of caring for a child with a chronic illness. Following the session, students were required to submit a written reflection on what they learned and the impact the session had on them. All reflections from one academic year were qualitatively analyzed by two investigators and organized using HyperRESEARCH software. A content analysis approach was used to generate codes and emergent themes. Two theoretical lenses guided the analyses: Arnold's framework on professional values and the lens of professional identity formation, described as a process by which health care professionals "think, act and feel like a physician. RESULTS: Students gained an appreciation of professional values, especially humanism and excellence, and how clinician role models reinforce these values. Reflective writings demonstrated recognition among learners that their identity involved being active participants in health care delivery and not just as passive classroom learners. Students were motivated to study diligently and be patient advocates; some questioned their skills in dealing with ambiguity and with the health-care system, resulting in a sense of helplessness. CONCLUSION: Students learn the importance of professional attributes and of clinician role models through a pediatric family teaching experience. They are motivated, displaying glimpses of their future role as caregivers and patient advocates; however, some also express fear and doubt their own abilities. Based on this, a debriefing session has been introduced to prevent a negative effect on learner self-efficacy.

Predictors of time to first cannulation for arteriovenous fistula in pediatric hemodialysis patients: Midwest Pediatric Nephrology Consortium study.

BACKGROUND: Permanent vascular access (PVA) is preferred for long-term hemodialysis. Arteriovenous fistulae (AVF) have the best patency and the lowest complication rates compared to arteriovenous grafts (AVG) and tunneled cuffed catheters (TCC). However, AVF need time to mature. This study aimed to investigate predictors of time to first cannulation for AVF in pediatric hemodialysis patients. METHODS: Data on first AVF and AVG of patients at 20 pediatric dialysis centers were collected retrospectively, including demographics, clinical information, dialysis markers, and surgical data. Statistical modeling was used to investigate predictors of outcome. RESULTS: First PVA was created in 117 children: 103 (88%) AVF and 14 (12%) AVG. Mean age at AVF creation was 15.0 ± 3.3 years. AVF successfully matured in 89 children (86.4%), and mean time to first cannulation was 3.6 ± 2.5 months. In a multivariable regression model, study center, age, duration of non-permanent vascular access (NPVA), and Kt/V at AVF creation predicted time to first cannulation, with study center as the strongest predictor (p < 0.01). Time to first cannulation decreased with increasing age (p = 0.03) and with increasing Kt/V (p = 0.01), and increased with duration of NPVA (p = 0.03). Secondary failure occurred in 10 AVF (11.8%). Time to first cannulation did not predict secondary failure (p = 0.29), but longer time to first cannulation tended towards longer secondary patency (p = 0.06). CONCLUSIONS: Study center is the strongest predictor of time to first cannulation for AVF and deserves further investigation. Time to first cannulation is significantly shorter in older children, with more efficient dialysis treatments, and increases with longer NPVA duration.

Skin Allergy to Azole Antifungal Agents for Systemic Use: A Review of the Literature.

BACKGROUND: Antifungal azoles are the first-line agents used to treat topical and, above all, systemic mycosis. The latter could be life-threating infections in immunocompromised patients. Chemotherapeutic antibiotics, including antifungal azoles, may induce hypersensitivity reactions; however, such immunologic adverse reactions have not been defined and carefully investigated. OBJECTIVE: The study aims to provide an update on the evaluation and diagnosis of skin allergy to azole antifungal agents. METHODS: This is a systematic review performed on PubMed and Google Schoolbarusing using the key terms "allergy, hypersensitivity, anaphylaxis, immediate-type reaction, delayed-type reaction, ketoconazole, fluconazole, posaconazole, voriconazole, itraconazole, triazoles, imidazoles, antifungals, antimycotics". The search strategy included meta-analyses, randomized controlled trials, clinical trials, observational studies, reviews and case reports. RESULTS: One hundred twenty-four articles matched our search terms. The most common adverse events reported were T-cell mediated delayed-type hypersensitivity reactions, fixed drug eruptions, exanthematous dermatitis, Steven-Johnson syndrome, toxic epidermal necrolysis and acute generalized exhanthematous pustulosis. Rarely a drug rash with eosinophilia systemic symptoms, has been described. Also, immediate-type reactions such as urticaria-angioedema or anaphylaxis have been reported following the administration of antifungal imidazoles, although not so frequently. CONCLUSION: Despite their widespread use, triazoles seem to induce rare cutaneous hypersensitivity reactions, but the pathomechanisms, risk factors, diagnostic and management strategies, including skin tests and challenge tests, are little known and poorly investigated.

Correction to: Predictors of patency for arteriovenous fistulae and grafts in pediatric hemodialysis patients.

The original version of this article unfortunately contained a mistake. The name of Vimal Chadha was presented incorrectly. The corrected author list is given above.