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.

Developing a Standardized Ethics Consultation Note Template Based on the Formatting Preferences of Stakeholders.

Effective documentation is considered a core competency for clinical ethics consultation. Ethics consultants within the Cleveland Clinic in Cleveland, Ohio, observed variation in the formatting of ethics chart notes across consultants and realized that this formatting was based on their own views of effectiveness. To minimize variation and optimize the readability and understandability of ethics chart notes for end users, a team undertook a quality improvement project to assess the formatting preferences of healthcare professionals who rely on ethics consultation notes. The team developed three sample templates and conducted interviews with stakeholders to understand their preferences. A single standardized template was developed based on the preferences that emerged, which all consultants on the ethics consultation service then utilized. In the first five months of implementation, the percentage of end user respondents marking the highest Likert scale option on a post-consultation survey regarding whether the ethics consultation service provided helpful documentation increased from 60 percent to 72 percent compared to the same five-month period in the year prior.

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.

American Indian Diabetes Beliefs and Practices: Anxiety, Fear, and Dread in Pregnant Women With Diabetes.

Diabetes among American Indian (AI) people is a health disparities condition that creates excessive morbidity and mortality. This research delineated culturally constructed models of type 2 diabetes among 97 pregnant women in two large AI nations in Oklahoma. The data analysis of explanatory models of type 2 diabetes revealed the participants' intense anxiety, fear, and dread related to the condition. The sample was further stratified by combinations of diabetes status: 1) absence of type 2 diabetes (n = 66), 2) type 2 diabetes prior to pregnancy (n = 4), and 3) gestational diabetes (n = 27). Patients were interviewed regarding perceptions of the etiology, course, and treatment of diabetes. The research incorporated an integrated phenomenologic and ethnographic approach using structured and semi-structured interviews to yield both quantitative and qualitative data. General findings comprised three main categories of patients' concerns regarding type 2 diabetes as an illness: 1) mechanical acts (i.e., injections), 2) medical complications, and 3) the conceptual sense of diabetes as a "severe" condition. Specific findings included significant fear and anxiety surrounding 1) the health and well-being of the unborn child, 2) the use of insulin injections, 3) blindness, 4) amputation, and 5) death. Paradoxically, although there was only a slight sense of disease severity overall, responses were punctuated with dread of specific outcomes. The latter finding is considered consistent with the presence of chronic diseases that can usually be managed but present risk of severe complications if not well controlled.

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.

Family members' requests to extend physiologic support after declaration of brain death: a case series analysis and proposed guidelines for clinical management.

We describe and analyze 13 cases handled by our ethics consultation service (ECS) in which families requested continuation of physiological support for loved ones after death by neurological criteria (DNC) had been declared. These ethics consultations took place between 2005 and 2013. Patients' ages ranged from 14 to 85. Continued mechanical ventilation was the focal intervention sought by all families. The ECS's advice and recommendations generally promoted "reasonable accommodation" of the requests, balancing compassion for grieving families with other ethical and moral concerns such as stewardship of resources, professional integrity, and moral distress. In cases we characterized as finite-goal accommodation, a "reasonable accommodation" strategy proved effective in balancing stakeholders' interests and goals, enabling steady progress toward resolution. When a family objected outright to a declaration of DNC and asked for an indefinite accommodation, the "reasonable accommodation" approach offered clinicians little practical direction, and resolution required definitive action by either the family or the clinical team. Based on our analysis and reflections on these 13 cases, we propose ethically justified and practical guidelines to assist healthcare professionals, administrators, and ECSs faced with similar cases.

Perceptions and Concerns Regarding Diabetes Mellitus During Pregnancy Among American Indian Women.

Diabetes among American Indian (AI) people is a. condition that creates excessive morbidity and mortality and is a significant health disparity. This research delineated culturally constructed models of diabetes mellitus (DM) among 97 pregnant women in 2 large AI Nations to Oklahoma. Analysis of data revealed intense anxiety, fear, and dread related to DM during pregnancy. The sample was stratified by DM status: (a) absence of DM (n = 66), (b) DM prior to pregnancy (n = 4), and (c) gestational (n = 27). Structured and semistructured interviews elicited patient culturally based explanatory models (EMs) of etiology, course, and treatment. The research incorporated an integrated phenomenologic and ethnographic approach and yielded both quantitative and qualitative data. General findings comprised the following main categories of patients' concerns regarding DM as an illness: (a) care-seeking behaviors, (b) medical management, (c) adherence and self-management, (d) complications, and (e) the conceptual sense of DM as a "severe" and feared condition. Many findings varied according to acculturation status, but all included significant fear and anxiety surrounding (a) the health and well-being of the unborn child, (b) the use of insulin injections, (c) blindness, (d) amputation, and (e) death, but with (f) a paradoxically lowered anxiety level about diabetes severity overall, while at the same time expressing extreme dread of specific outcomes. The latter finding is considered consistent with the presence of chronic conditions that can usually be managed, yet still having risk if severe.

Denying Death: The Terminally Critically Ill.

We describe a subgroup of the Chronically Critically Ill (CCI) we call the Terminally Critically Ill as demonstrated by terminally ill cancer patients. These cancer patients, though clearly terminally ill and with relatively short prognoses, can be kept alive for extended periods with medical interventions aimed at treating the complications of the cancer and cancer treatment. Such interventions can be painful, exhausting, costly and may interfere with attending to end of life concerns. We present a typical (composite) case and discuss ethical concerns regarding this growing subgroup of the chronically critically ill patients for whom death is routinely denied and delayed for extended periods.

Blue and green ammonia production: A techno-economic and life cycle assessment perspective.

Blue and green ammonia production have been proposed as low-carbon alternatives to emissions-intensive conventional ammonia production. Although much attention has been given to comparing these alternatives, it is still not clear which process has better environmental and economic performance. We present a techno-economic analysis and full life cycle assessment to compare the economics and environmental impacts of blue and green ammonia production. We address the importance of time horizon in climate change impact comparisons by employing the Technology Warming Potential, showing that methane leakage can exacerbate the climate change impacts of blue ammonia in short time horizons. We represent a constrained renewable electricity availability scenario by comparing the climate change impact mitigation efficiency per kWh of renewable electricity. Our work emphasizes the importance of maintaining low natural gas leakage for sustainability of blue ammonia, and the potential for technological advances to further reduce the environmental impacts of photovoltaics-based green ammonia.

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.

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.

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.

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.

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.

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.

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.

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.