Burnout During the COVID-19 Pandemic: A Report on Pediatric Residents.

BACKGROUND AND OBJECTIVE: The Pediatric Resident Burnout and Resilience Consortium (PRB-RSC) has described the epidemiology of burnout in pediatric residents since 2016. We hypothesized burnout rates during the pandemic would increase. We explored resident burnout during the COVID-19 pandemic and its relationship to resident perception of workload, training, personal life, and local COVID burden. METHODS: Since 2016, PRB-RSC has sent an annual, confidential survey to over 30 pediatric and medicine-pediatrics residencies. In 2020 and 2021, seven questions were added to explore the relationship of COVID-19 and perceptions of workload, training, and personal life. RESULTS: In 2019, 46 programs participated, 22 in 2020, and 45 in 2021. Response rates in 2020 (n = 1055, 68%) and 2021(n = 1702, 55%) were similar to those of previous years (P = .09). Burnout rates in 2020 were significantly lower than in 2019 (54% vs 66%, P < .001) but returned to pre-COVID levels in 2021 (65%, P = .90). In combined 2020-2021 data, higher rates of burnout were associated with reported increased workload (Adjusted Odds Ratio (AOR) 1.38, 95% CI 1.19-1.6) and concerns regarding the effect of COVID on training (AOR 1.35, 95% CI 1.2-1.53). Program-level county COVID burden in combined 2020-2021 data was not associated with burnout in this model (AOR=1.03, 95% CI 0.70-1.52). CONCLUSIONS: Burnout rates within reporting programs decreased significantly in 2020 and returned to prepandemic levels in 2021. Increased burnout was associated with perceived increases in workload and concerns regarding effect of the pandemic on training. Given these findings, programs should consider further investigation into workload and training uncertainty on burnout.

Seeking justice, equity, diversity and inclusion in pediatric nephrology.

Inequity, racism, and health care disparities negatively impact the well-being of children with kidney disease. This review defines social determinants of health and describes how they impact pediatric nephrology care; outlines the specific impact of systemic biases and racism on chronic kidney disease care and transplant outcomes; characterizes and critiques the diversity of the current pediatric nephrology workforce; and aims to provide strategies to acknowledge and dismantle bias, address barriers to care, improve diversity in recruitment, and strengthen the pediatric nephrology community. By recognizing historical and current realities and limitations, we can move forward with strategies to address racism and bias in our field and clinical practices, thereby cultivating inclusive training and practice environments.

Burnout in Pediatric Nephrology Fellows and Faculty: Lessons From the Sustainable Pediatric Nephrology Workforce Project (SUPERPOWER).

Physician well-being is an important contributor to both job satisfaction and patient outcomes. Rates of burnout among physicians vary by specialty, ranging from 35 to 70%. Among pediatric residents, longitudinal data demonstrates consistent rates of burnout around 50-60%, although little is known about burnout among pediatric subspecialty fellows. Specifically, the degree of burnout among pediatric nephrologists remains unknown, as does the impact faculty burnout may have on trainee burnout. We sought to evaluate prevalence and predictors of burnout among US pediatric nephrology fellows and faculty, and assess for interactions between groups. In this multi-center pilot survey of all United States pediatric nephrology training programs from February to April 2020, burnout was assessed through abbreviated Maslach Burnout Inventory and predictors were explored through survey items devoted to demographic, personal characteristics, and job and career satisfaction questions. A total of 30/34 available fellows and 86/102 faculty from 11 institutions completed the survey (overall response rate 85%). The prevalence of burnout was 13% among fellows and 16% among faculty. Demographic (age, gender, year of training, faculty rank, marital status) and program factors (fellowship size, faculty size, current block/rotation, vacation or weekend off timing) were not significantly associated with burnout. Faculty and fellows with burnout reported significantly lower quality of life (5.3 vs. 7.9, p < 0.05), higher perceived stress (2.4 vs. 1.4, p < 0.05) and lower satisfaction with career choice (66 vs. 22%) and work life balance (28 vs. 0%), compared to those without burnout (p < 0.05 for all). Other important factors positively associated with burnout included lower institutional support for wellness programs and lower satisfaction with both colleague and faculty support. Larger studies are needed to explore if burnout is truly less prevalent among pediatric nephrology fellows and faculty compared to pediatric residents and graduate physicians. A larger sample size is also necessary to determine whether any interactions exist between the faculty and trainee roles in the developments of burnout. Future studies should also explore how to promote well-being through addressing key factors such as overall learning/working environment, stress reduction, and building personal resilience.

Realizing Inclusion and Systemic Equity in Medicine: Upstanding in the Medical Workplace (RISE UP)-an Antibias Curriculum.

Introduction: Racism is a public health threat, and racist behaviors adversely affect clinicians in addition to patients. Medical trainees commonly experience racism and bias. More than half of pediatric residents at a single institution reported experiencing or witnessing discriminatory behavior at work; only 50% reported receiving training on implicit bias, delivering difficult feedback, or peer support. Our multispecialty team created Realizing Inclusion and Systemic Equity in Medicine: Upstanding in the Medical Workplace (RISE UP), an antibias, anti-racism communication curriculum composed of three hybrid (virtual and in-person) workshops. Methods: During the pediatric resident workshops, we introduced tools for addressing bias, presented video simulations, and led small-group debriefings with guided role-play. We also reviewed escalation pathways, reporting methods, and support systems. Residents completed an evaluation before and after each workshop to assess the curriculum's efficacy. Results: Thirty-nine residents participated in RISE UP, with 20 attending all three workshops. Ninety-six percent of participants indicated they would recommend the workshops to colleagues. After the third workshop, 92% reported having tools to respond to bias, and 85% reported knowing how to escalate concerns regarding discriminatory behavior. Chief residents were most frequently identified as sources of resident support when encountering discriminatory behavior. Discussion: This curriculum was successful in developing and strengthening residents' responses to discrimination, including upstander support. The curriculum is adaptable for virtual, in-person, and hybrid settings, allowing for flexibility. Establishing institutional support, promoting faculty development, and creating and disseminating escalation pathways are critical to addressing racism in health care.

Longitudinal outcomes of body mass index in overweight and obese children with chronic kidney disease.

BACKGROUND: Longitudinal changes in body mass index (BMI) among overweight and obese children with chronic kidney disease (CKD) are not well characterized. We studied longitudinal trajectories and correlates of these trajectories, as results may identify opportunities to optimize health outcomes. METHODS: Longitudinal changes in age-sex-specific BMI z-scores over 1851 person-years of follow-up were assessed in 524 participants of the Chronic Kidney Disease in Children Study. A total of 353 participants were categorized as normal (BMI > 5th to < 85th percentile), 56 overweight (BMI ≥ 85th to 95th percentile) and 115 obese (BMI ≥ 95th percentile) based on the average of three BMI measurements during the first year of follow-up. Studied covariates included age, sex, race, CKD etiology, corticosteroid usage, household income, and maternal education. RESULTS: In unadjusted analysis, BMI z-scores decreased over time in elevated BMI groups (overweight: mean = - 0.06 standard deviations (SD) per year, 95% CI: - 0.11, - 0.01; obese: mean = - 0.04 SD per year, 95% CI: - 0.07, - 0.01). Among obese children, only age was associated with change in BMI z-score; children < 6 years had a mean decrease of 0.19 SD during follow-up (95% CI: - 0.30, - 0.09). Socioeconomic factors were not associated with change in BMI. CONCLUSION: Overweight and obese children with CKD demonstrated a significant annual decline in BMI, though the absolute change was modest. Among obese children, only age < 6 years was associated with significant decline in BMI. Persistence of elevated BMI in older children and adolescents with CKD underscores the need for early prevention and effective intervention.

Assessment of the Urinary Microbiome in Children Younger Than 48 Months.

BACKGROUND: The urinary tract was once thought to be sterile, and little is known about the urinary microbiome in children. This study aimed to examine the urinary microbiome of young children across demographic and clinical factors. METHODS: Children <48 months, undergoing a urinary catheterization for clinical purposes in the Pediatric Emergency Department were recruited and urine samples collected. Detailed demographic and clinical information were recorded. Urine samples underwent DNA extraction and 16S ribosomal RNA gene sequencing, urinalysis and urine culture. RESULTS: Eighty-five children were included; a urinary microbiome was identified in every child. Nine children had Escherichia coli urinary tract infections (UTIs) identified. Those with UTIs had a significantly decreased alpha diversity (t test, P < 0.001) and the composition of the microbiome clustered separately (P = 0.001) compared with those without UTIs. CONCLUSIONS: A urinary microbiome was identified in every child, even neonates. Differences in microbiome diversity and composition were observed in patients with a standard culture positive UTI. The urinary microbiome has just begun to be explored, and the implications on long-term disease processes deserve further investigation.

Bartter Syndrome and Gitelman Syndrome.

Bartter and Gitelman syndromes are conditions characterized by renal salt-wasting. Clinical presentations range from severe antenatal disease to asymptomatic with incidental diagnosis. Hypokalemic hypochloremic metabolic alkalosis is the common feature. Bartter variants may be associated with polyuria and weakness. Gitelman syndrome is often subtle, and typically diagnosed later life with incidental hypokalemia and hypomagnesemia. Treatment may involve fluid and electrolyte replenishment, prostaglandin inhibition, and renin-angiotensin-aldosterone system axis disruption. Investigators have identified causative mutations but genotypic-phenotypic correlations are still being characterized. Collaborative registries will allow improved classification schema and development of effective treatments.

Neonate with urinary ascites but no hydronephrosis: unusual presentation of posterior urethral valves.

Posterior urethral valves (PUV) are an important cause of paediatric obstructive uropathy. PUV are usually diagnosed by prenatal ultrasonography (US) revealing hydronephrosis and bladder distention. We describe a 17-day-old male infant with abdominal distention who had no hydronephrosis on prenatal US. Laboratory investigations showed serum creatinine of 12 mg/dL, hyperkalaemia and metabolic acidosis. Abdominal US showed large amount of ascites, normal-sized kidneys without hydronephrosis and incompletely distended bladder. Paracentesis revealed clear, yellow ascitic fluid with creatinine level of 27 mg/dL compatible with urinary ascites. Voiding cystourethrogram (VCUG) demonstrated PUV with a dilated posterior urethra, grade 5 right vesicoureteral reflux and a ruptured kidney fornix with peritoneal extravasation of contrast. Foley decompression resulted in normalisation of creatinine within 72 hours. Transurethral resection of PUV was performed, and a repeat VCUG showed recovery of forniceal rupture. This case illustrates an unusual presentation of a potentially life-threatening but treatable cause of urinary tract obstruction.

Phenotypic and Genotypic Characterization and Treatment of a Cohort With Familial Tumoral Calcinosis/Hyperostosis-Hyperphosphatemia Syndrome.

Familial tumoral calcinosis (FTC)/hyperostosis-hyperphosphatemia syndrome (HHS) is a rare disorder caused by mutations in the genes encoding fibroblast growth factor-23 (FGF23), N-acetylgalactosaminyltransferase 3 (GALNT3), or KLOTHO. The result is functional deficiency of, or resistance to, intact FGF23 (iFGF23), causing hyperphosphatemia, increased renal tubular reabsorption of phosphorus (TRP), elevated or inappropriately normal 1,25-dihydroxyvitamin D3 (1,25D), ectopic calcifications, and/or diaphyseal hyperostosis. Eight subjects with FTC/HHS were studied and treated. Clinical manifestations varied, even within families, ranging from asymptomatic to large, disabling calcifications. All subjects had hyperphosphatemia, increased TRP, and elevated or inappropriately normal 1,25D. C-terminal FGF23 was markedly elevated whereas iFGF23 was comparatively low, consistent with increased FGF23 cleavage. Radiographs ranged from diaphyseal hyperostosis to massive calcification. Two subjects with severe calcifications also had overwhelming systemic inflammation and elevated C-reactive protein (CRP). GALNT3 mutations were identified in seven subjects; no causative mutation was found in the eighth. Biopsies from four subjects showed ectopic calcification and chronic inflammation, with areas of heterotopic ossification observed in one subject. Treatment with low phosphate diet, phosphate binders, and phosphaturia-inducing therapies was prescribed with variable response. One subject experienced complete resolution of a calcific mass after 13 months of medical treatment. In the two subjects with systemic inflammation, interleukin-1 (IL-1) antagonists significantly decreased CRP levels with resolution of calcinosis cutis and perilesional inflammation in one subject and improvement of overall well-being in both subjects. This cohort expands the phenotype and genotype of FTC/HHS and demonstrates the range of clinical manifestations despite similar biochemical profiles and genetic mutations. Overwhelming systemic inflammation has not been described previously in FTC/HHS; the response to IL-1 antagonists suggests that anti-inflammatory drugs may be useful adjuvants. In addition, this is the first description of heterotopic ossification reported in FTC/HHS, possibly mediated by the adjacent inflammation. © 2016 American Society for Bone and Mineral Research.

Perceived appetite and clinical outcomes in children with chronic kidney disease.

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.

Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia.

Alterations in epithelial cell polarity and in the subcellular distributions of epithelial ion transport proteins are key molecular consequences of acute kidney injury and intracellular energy depletion. AMP-activated protein kinase (AMPK), a cellular energy sensor, is rapidly activated in response to renal ischemia, and we demonstrate that its activity is upregulated by energy depletion in Madin-Darby canine kidney (MDCK) cells. We hypothesized that AMPK activity may influence the maintenance or recovery of epithelial cell organization in mammalian renal epithelial cells subjected to energy depletion. MDCK cells were ATP depleted through a 1-h incubation with antimycin A and 2-deoxyglucose. Immunofluoresence localization demonstrated that this regimen induces mislocalization of the Na-K-ATPase from its normal residence at the basolateral plasma membrane to intracellular vesicular compartments. When cells were pretreated with the AMPK activator metformin before energy depletion, basolateral localization of Na-K-ATPase was preserved. In MDCK cells in which AMPK expression was stably knocked down with short hairpin RNA, preactivation of AMPK with metformin did not prevent Na-K-ATPase redistribution in response to energy depletion. In vivo studies demonstrate that metformin activated renal AMPK and that treatment with metformin before renal ischemia preserved cellular integrity, preserved Na-K-ATPase localization, and led to reduced levels of neutrophil gelatinase-associated lipocalin, a biomarker of tubular injury. Thus AMPK may play a role in preserving the functional integrity of epithelial plasma membrane domains in the face of energy depletion. Furthermore, pretreatment with an AMPK activator before ischemia may attenuate the severity of renal tubular injury in the context of acute kidney injury.

Activating AMP-activated protein kinase (AMPK) slows renal cystogenesis.

Renal cyst development and expansion in autosomal dominant polycystic kidney disease (ADPKD) involves both fluid secretion and abnormal proliferation of cyst-lining epithelial cells. The chloride channel of the cystic fibrosis transmembrane conductance regulator (CFTR) participates in secretion of cyst fluid, and the mammalian target of rapamycin (mTOR) pathway may drive proliferation of cyst epithelial cells. CFTR and mTOR are both negatively regulated by AMP-activated protein kinase (AMPK). Metformin, a drug in wide clinical use, is a pharmacological activator of AMPK. We find that metformin stimulates AMPK, resulting in inhibition of both CFTR and the mTOR pathways. Metformin induces significant arrest of cystic growth in both in vitro and ex vivo models of renal cystogenesis. In addition, metformin administration produces a significant decrease in the cystic index in two mouse models of ADPKD. Our results suggest a possible role for AMPK activation in slowing renal cystogenesis as well as the potential for therapeutic application of metformin in the context of ADPKD.

AS160 associates with the Na+,K+-ATPase and mediates the adenosine monophosphate-stimulated protein kinase-dependent regulation of sodium pump surface expression.

The Na(+),K(+)-ATPase is the major active transport protein found in the plasma membranes of most epithelial cell types. The regulation of Na(+),K(+)-ATPase activity involves a variety of mechanisms, including regulated endocytosis and recycling. Our efforts to identify novel Na(+),K(+)-ATPase binding partners revealed a direct association between the Na(+),K(+)-ATPase and AS160, a Rab-GTPase-activating protein. In COS cells, coexpression of AS160 and Na(+),K(+)-ATPase led to the intracellular retention of the sodium pump. We find that AS160 interacts with the large cytoplasmic NP domain of the α-subunit of the Na(+),K(+)-ATPase. Inhibition of the activity of the adenosine monophosphate-stimulated protein kinase (AMPK) in Madin-Darby canine kidney cells through treatment with Compound C induces Na(+),K(+)-ATPase endocytosis. This effect of Compound C is prevented through the short hairpin RNA-mediated knockdown of AS160, demonstrating that AMPK and AS160 participate in a common pathway to modulate the cell surface expression of the Na(+),K(+)-ATPase.

Hematuria and decreased kidney function as initial signs of acute B-cell lymphoblastic leukemia.

We report the case of a 14-year-old boy who presented with hematuria and decreased kidney function as initial manifestations of acute lymphoblastic leukemia (ALL). Computed tomography of the abdomen showed extensive retroperitoneal lymphadenopathy and bilateral nephromegaly. The patient's kidney biopsy specimen showed a dense monomorphous interstitial infiltrate of small round blue cells with significant nuclear atypia. Immunohistochemical workup showed positive staining for CD20, CD10, and terminal deoxynucleotidyl transferase (TdT), consistent with ALL. The patient underwent induction chemotherapy, attained remission 4 weeks after induction, and presently is stable in the consolidation phase of chemotherapy. This is an unusual case of ALL involving both kidneys with initial presenting signs of hematuria and decreased kidney function.

Mycophenolate mofetil-induced colitis in children.

Mycophenolate Mofetil (MMF) is a frequently used medication for the maintenance of immunosuppression in pediatric renal transplant patients. It is known to cause mild gastrointestinal side effects. Severe colitis due to MMF is rare and is only described in adults. We report 2 children who presented with severe colitis due to MMF. Infectious and other causes of diarrhea were ruled out. Our patients had diverse histologic findings on colonic biopsies. Patient 1 had histologic features similar to inflammatory bowel disease and patient 2 to graft versus host disease. Withdrawal of MMF resulted in the complete resolution of symptoms in both patients suggesting a causal association. These cases underscore the importance of considering MMF-induced colitis in any patient who presents with diarrhea while on MMF therapy.

Dystroglycan and AMP kinase: polarity's protectors when the power goes out.

The AMP-stimulated protein kinase regulates epithelial polarity under conditions of energy depletion by phosphorylating the myosin regulatory light chain. In this issue of Developmental Cell, Mirouse et al. demonstrate that dystroglycan and perlecan, an extracellular matrix receptor and its ligand, help localize myosin regulatory light chain, making it available for phosphorylation by AMP kinase in response to energy stress.

Epithelial junctions and polarity: complexes and kinases.

PURPOSE OF REVIEW: An enormous body of research has been focused on exploring the mechanisms through which epithelial cells establish their characteristic polarity. It is clear that under normal circumstances cell-cell contacts mediated by the calcium-dependent adhesion proteins of the intercellular adhesion junctions are required to initiate complete polarization. Furthermore, formation of the tight, or occluding, junctions that limit paracellular permeability has long been thought to help to establish polarity by preventing the diffusion of membrane proteins between the two plasmalemmal domains. This review will discuss several selected kinases and protein complexes and highlight their relevance to transporting epithelial cell polarization. RECENT FINDINGS: Recent work has shed new light on the roles of junctional complexes in establishing and maintaining epithelial cell polarity. In addition, work from several laboratories suggests that the formation of these junctions is tied to processes that regulate cellular energy metabolism. SUMMARY: Junctional complexes and energy sensing kinases constitute a novel class of machinery whose capacity to generate and modulate epithelial cell polarity is likely to have wide ranging and important physiological ramifications.

Pediatric fatality following ingestion of dinitrophenol: postmortem identification of a "dietary supplement".

Dinitrophenol, a chemical currently used as an insecticide, is known to uncouple mitochondrial oxidative phosphorylation. A component of explosives, it has also been used in the past as a food coloring and clothing dye. In the 1930s, physicians prescribed it for weight loss, but this practice was discontinued when reports of cataracts, deaths, and other adverse outcomes came to light. We describe in our report the overdose and fatality of a teenager who purchased the product as a weight loss dietary supplement by mail order. We also describe a laboratory method that allowed postmortem determination of the dinitrophenol concentration in the victim's serum. Her death, despite prompt medical treatment, underscores the danger of dinitrophenol. The easy accessibility and apparent resurgent interest in dinitrophenol as a weight loss agent is extremely timely and troubling.