First name
Sandra
Last name
Amaral

Title

Pediatric Kidney Transplantation-Can We Do Better? The Promise and Limitations of Epitope/Eplet Matching.

Year of Publication

2022

Number of Pages

893002

Date Published

07/2022

ISSN Number

2296-2360

Abstract

Kidney transplant is the optimal treatment for end-stage kidney disease as it offers significant survival and quality of life advantages over dialysis. While recent advances have significantly improved early graft outcomes, long-term overall graft survival has remained largely unchanged for the last 20 years. Due to the young age at which children receive their first transplant, most children will require multiple transplants during their lifetime. Each subsequent transplant becomes more difficult because of the development of donor specific HLA antibodies (dnDSA), thereby limiting the donor pool and increasing mortality and morbidity due to longer time on dialysis awaiting re-transplantation. Secondary prevention of dnDSA through increased post-transplant immunosuppression in children is constrained by a significant risk for viral and oncologic complications. There are currently no FDA-approved therapies that can meaningfully reduce dnDSA burden or improve long-term allograft outcomes. Therefore, primary prevention strategies aimed at reducing the risk of dnDSA formation would allow for the best possible long-term allograft outcomes without the adverse complications associated with over-immunosuppression. Epitope matching, which provides a more nuanced assessment of immunological compatibility between donor and recipient, offers the potential for improved donor selection. Although epitope matching is promising, it has not yet been readily applied in the clinical setting. Our review will describe current strengths and limitations of epitope matching software, the evidence for and against improved outcomes with epitope matching, discussion of eplet load vs. variable immunogenicity, and conclude with a discussion of the delicate balance of improving matching without disadvantaging certain populations.

DOI

10.3389/fped.2022.893002

Alternate Title

Front Pediatr

PMID

35722502

Title

5-Year Activity and Participation Outcomes of the First Successful Pediatric Bilateral Hand Transplantation: A Case Report.

Year of Publication

2022

Number of Pages

1-16

Date Published

2022 Apr 04

ISSN Number

1541-3144

Abstract

<p><strong>AIMS: </strong>Describe the 5-year outcomes of the first successful pediatric bilateral hand transplantation.</p>

<p><strong>METHODS: </strong>The child underwent quadrimembral amputation at age two and received bilateral hand allografts at age eight. Rehabilitation included biomechanical, neurorehabilitation, and occupational approaches in acute and outpatient settings. Therapist observed outcomes, patient-reported measures, and parent-reported measures were repeated over a 5-year period.</p>

<p><strong>RESULTS: </strong>Observation assessments revealed functional dexterity skills and modified independence to full independence with self-care activities. The parent reported the child had moderate difficulty with upper extremity functioning 25-, 41-, and 48-months post-transplantation, and mild difficulty at 60-months; the child reported no difficulties in this domain at 41 months. Five years post-transplantation the child reported enjoying many age-appropriate activities, and high-quality peer relations were endorsed by both parent and child.</p>

<p><strong>CONCLUSION: </strong>The child developed hand movements for daily activities and was completing daily activities with improved efficiency. Health-related quality of life outcomes were favorable.</p>

DOI

10.1080/01942638.2022.2057210

Alternate Title

Phys Occup Ther Pediatr

PMID

35379065

Title

Text Messages and Financial Incentives to Increase Physical Activity in Adolescents With Prediabetes and Type 2 Diabetes: Web-Based Group Interviews to Inform Intervention Design.

Year of Publication

2022

Number of Pages

e33082

Date Published

2022 Apr 06

ISSN Number

2371-4379

Abstract

<p><strong>BACKGROUND: </strong>Physical activity is a major component of treatment for adolescents with obesity and prediabetes or type 2 diabetes; however, sedentary behavior remains pervasive. An SMS text message-based intervention paired with financial incentives may be an effective way to promote physical activity in this population.</p>

<p><strong>OBJECTIVE: </strong>This study aims to obtain end-user feedback on SMS text message content and assess the acceptability of a planned SMS text messaging intervention with financial incentives to motivate youth with prediabetes or type 2 diabetes to increase physical activity.</p>

<p><strong>METHODS: </strong>Adolescents with overweight or obesity and prediabetes or type 2 diabetes who attended a large academic pediatric endocrinology clinic were recruited to participate in group interviews (2-4/group) via videoconferencing. Participants were asked to share their thoughts on the use of SMS text messages and financial incentives to remind and motivate them to be more physically active. They rated and provided feedback on specific messages to be used in clinical trials. Participants were also asked about their personal experience with rewards to motivate behavior change and their anticipated reactions to rewards provided for goal attainment (gain-framing) versus those provided and then taken away if a goal was not met (loss-framing). The interviews were conducted by 2 trained interviewers and a note-taker. Content analysis was used to explore themes.</p>

<p><strong>RESULTS: </strong>Group interviews were completed with 20 participants (11/20, 55% women; 15/20, 75% with type 2 diabetes; 5/20, 25% with prediabetes) with a mean age of 15 (SD 1; range 12-18) years and a mean BMI of 41 (SD 5) kg/m (all &gt;95th percentile for age and sex). Most participants were non-Hispanic Black (14/20, 70%) and 10% (2/20) were Hispanics. Participants frequently cited near-continuous smartphone use and agreed that SMS text messages would serve as good reminders to be physically active, but the consensus about the need for short messages was strong. Favorable content included references to what they were likely to be doing when messages were sent (eg, homework or watching television) and messages that were upbeat or informative. Specific physical activity suggestions were rated favorably. Attitudes toward financial incentives varied, with differing opinions about whether loss-framed incentives would be motivating or discouraging. Many participants highlighted the role of intrinsic, rather than extrinsic, motivation in achieving and sustaining behavior change.</p>

<p><strong>CONCLUSIONS: </strong>The engagement of adolescents with obesity and diabetes or prediabetes allowed for the refinement of SMS text messages for our planned intervention, with an emphasis on short, upbeat, relatable, and informative messages. Although an SMS text messaging intervention using financial incentives to motivate youth with prediabetes or type 2 diabetes to be more physically active is theoretically acceptable, the impact on actual activity levels in this population requires prospective evaluation in a clinical trial.</p>

DOI

10.2196/33082

Alternate Title

JMIR Diabetes

PMID

35384850

Title

Focal segmental glomerulosclerosis recurrence in a young adult with kidney transplant after mRNA COVID-19 vaccination.

Year of Publication

2022

Date Published

2022 Apr 29

ISSN Number

1432-198X

DOI

10.1007/s00467-022-05564-8

Alternate Title

Pediatr Nephrol

PMID

35486256

Title

Self-Reported Health Outcomes of Children and Youth with 10 Chronic Diseases.

Year of Publication

2022

Date Published

2022 Mar 02

ISSN Number

1097-6833

Abstract

<p><strong>OBJECTIVES: </strong>To identify pediatric patient-reported outcomes (PROs) that are associated with chronic conditions and to evaluate the effects of chronic disease activity on PROs.</p>

<p><strong>STUDY DESIGN: </strong>Participants 8-24 years-old and their parents were enrolled into 14 studies that evaluated PROMIS® PROs across 10 chronic conditions--asthma, atopic dermatitis, cancer, cancer survivors, chronic kidney disease, Crohn's disease, juvenile idiopathic arthritis, lupus, sickle cell disease, and type 1 diabetes mellitus. PRO scores were contrasted with the United States general population of children using nationally representative percentiles. PRO-specific coefficients of variation were computed to illustrate the degree of variation in scores within versus between conditions. Condition-specific measures of disease severity and Cohens d effect sizes were used to examine PRO scores by disease activity.</p>

<p><strong>RESULTS: </strong>Participants included 2,975 child respondents and 2,392 parent respondents who provided data for 3,409 unique children: 52% were 5-12 years-old, 52% female, 25% African-American/Black, and 14% Hispanic. Across all 10 chronic conditions, children reported more anxiety, fatigue, pain, and mobility restrictions than the general pediatric population. Variation in PRO scores within chronic disease cohorts was equivalent to variation within the general population, exceeding between-cohort variation by factors of 1.9 (mobility) to 5.7 (anxiety). Disease activity was consistently associated with poorer self-reported health, and these effects were weakest for peer relationships.</p>

<p><strong>CONCLUSIONS: </strong>Chronic conditions are associated with symptoms and functional status in children and adolescents across 10 different disorders. These findings highlight the need to complement conventional clinical evaluations with those obtained directly from patients themselves using PROs.</p>

DOI

10.1016/j.jpeds.2022.02.052

Alternate Title

J Pediatr

PMID

35247394

Title

Caregiver perspectives of pre-transplant evaluation in children.

Year of Publication

2022

Date Published

2022 Jan 05

ISSN Number

1432-198X

Abstract

<p><strong>BACKGROUND: </strong>Pre-transplant evaluation is mandated by Centers for Medicare and Medicaid Services, but there is wide institutional variation in implementation, and the family experience of the process is incompletely understood. Current literature largely focuses on adult transplant recipients.</p>

<p><strong>METHODS: </strong>This qualitative study begins to fill the knowledge gap about family experience of the pre-transplant evaluation for children through interviews with caregivers at a large pediatric transplant center.</p>

<p><strong>RESULTS: </strong>Prominent themes heard from caregivers include (1) the pre-transplant evaluation is overwhelming and emotional, (2) prior experiences and background knowledge frame the evaluation experience, and (3) frustration with communication among teams is common.</p>

<p><strong>CONCLUSIONS: </strong>These findings are relevant to efforts by transplant centers to optimize information delivery, minimize concrete barriers, and address healthcare systems issues. A higher resolution version of the Graphical abstract is available as Supplementary information.</p>

DOI

10.1007/s00467-021-05354-8

Alternate Title

Pediatr Nephrol

PMID

34985556

Title

A Qualitative Study of Facilitators and Barriers to Self-Management of CKD.

Year of Publication

2022

Number of Pages

46-55

Date Published

2022 Jan

ISSN Number

2468-0249

Abstract

<p><strong>Introduction: </strong>Self-management is an integral component of CKD treatment. Nevertheless, many patients with CKD do not adequately engage in self-management behaviors, and little is known on the underlying reasons. We aimed to identify and describe the factors that influence self-management behaviors from the perspective of adults with CKD.</p>

<p><strong>Methods: </strong>We conducted 30 semistructured interviews with adults with CKD stage 3 or 4 from an academic nephrology clinic in the United States. Interviews were analyzed thematically.</p>

<p><strong>Results: </strong>The following are the 3 key phases of CKD self-management behavior engagement identified: (i) prioritization, (ii) performance, and (iii) maintenance. Prioritization was favorably influenced by optimism, stress management, and patient-provider communication and hampered by fatalism and competing priorities. Behavior performance was facilitated by motivating factors, self-efficacy, and support resources and impeded by comorbid conditions that caused treatment burden and adverse symptoms. Behavior maintenance relied on effective routines, influenced by similar factors as behavior performance, and reinforced by memory aids, goal setting, self-monitoring, and proactive preparation.</p>

<p><strong>Conclusion: </strong>We identified modifiable facilitators and barriers that influence the incorporation of CKD self-management into daily life. Our findings have important implications for the care of patients with CKD by providing a framework for providers to develop effective, tailored approaches to promote self-management engagement.</p>

DOI

10.1016/j.ekir.2021.10.021

Alternate Title

Kidney Int Rep

PMID

35005313

Title

Late renal allograft torsion in a pediatric transplant recipient.

Year of Publication

2021

Number of Pages

e14210

Date Published

2021 Dec 15

ISSN Number

1399-3046

Abstract

<p><strong>BACKGROUND: </strong>Kidney allograft torsion is a rare complication of kidney transplant that can lead to allograft loss from prolonged ischemia if not quickly corrected with detorsion and nephropexy. We report a case of late intraperitoneal renal allograft torsion in a pediatric transplant recipient.</p>

<p><strong>CASE REPORT: </strong>The patient is a 7-year-old male with a history of end-stage renal disease secondary to renal dysplasia in the setting of bilateral high-grade vesicoureteral reflux. He underwent bilateral native nephrectomies for recurrent pyelonephritis and right ureteral kink with urinary tract obstruction. Torsion occurred 3&nbsp;years after transplant in the setting of one day of emesis, loose stool, severe abdominal pain, and decreased urine output. Diagnosis of transplant torsion was suspected on non-contrast CT scan done after transplant Doppler ultrasound showed no flow to the allograft. The CT scan showed that the kidney had been medialized and renal hilum was flipped from the expected orientation. The patient required a transplant nephrectomy.</p>

<p><strong>CONCLUSIONS: </strong>Renal transplant torsion is a rare event but should be suspected in any renal transplant recipient with acute onset of abdominal pain, acute kidney injury, and decreased urine output, regardless of length of time from transplantation. Patients suspected to have renal torsion should be evaluated emergently with a transplant ultrasound Doppler.</p>

DOI

10.1111/petr.14210

Alternate Title

Pediatr Transplant

PMID

34907635

Title

Patient-Reported Outcomes in Children With Chronic Kidney Disease.

Year of Publication

2021

Number of Pages

476-484

Date Published

2021 Sep

ISSN Number

1558-4488

Abstract

<p>Patient-reported outcomes (PROs) are quantitative assessments of a patient's perspective on their health and are derived directly from the patient, as opposed to clinician interpretation. PROs can serve as unique tools to improve health care providers' understanding of the patient's daily lived experience and highlight salient domains that are specific to children with chronic kidney disease (CKD). As such, PROs fill an important gap in achieving optimal health and well-being for children with CKD. However, several knowledge gaps remain in the implementation of PROs within both the clinical and research realms. This review provides a broad overview of PRO development, implementation for children with CKD, and highlights future directions and challenges.</p>

DOI

10.1016/j.semnephrol.2021.09.010

Alternate Title

Semin Nephrol

PMID

34916009

Title

Design and Methods of the Validating Injury to the Renal Transplant Using Urinary Signatures (VIRTUUS) Study in Children.

Year of Publication

2021

Number of Pages

e791

Date Published

2021 Dec

ISSN Number

2373-8731

Abstract

<p>Lack of noninvasive diagnostic and prognostic biomarkers to reliably detect early allograft injury poses a major hindrance to long-term allograft survival in pediatric kidney transplant recipients.</p>

<p><strong>Methods: </strong>Validating Injury to the Renal Transplant Using Urinary Signatures Children's Study, a North American multicenter prospective cohort study of pediatric kidney transplant recipients, aims to validate urinary cell mRNA and metabolite profiles that were diagnostic and prognostic of acute cellular rejection (ACR) and BK virus nephropathy (BKVN) in adult kidney transplant recipients in Clinical Trials in Organ Transplantation-4. Specifically, we are investigating: (1) whether a urinary cell mRNA 3-gene signature (-normalized mRNA, and ribosomal RNA) discriminates biopsies with versus without ACR, (2) whether a combined metabolite profile with the 3-gene signature increases sensitivity and specificity of diagnosis and prognostication of ACR, and (3) whether mRNA levels in urinary cells are diagnostic of BKVN and prognostic for allograft failure.</p>

<p><strong>Results: </strong>To date, 204 subjects are enrolled, with 1405 urine samples, including 144 biopsy-associated samples. Among 424 urine samples processed for mRNA, the median A260:280 ratio (RNA purity) was 1.91, comparable with Clinical Trials in Organ Transplantation-4 (median 1.82). The quality control failure rate was 10%. Preliminary results from urine supernatant showed that our metabolomics platform successfully captured a broad array of metabolites. Clustering of pool samples and overlay of samples from various batches demonstrated platform robustness. No study site effect was noted.</p>

<p><strong>Conclusions: </strong>Multicenter efforts to ascertain urinary biomarkers in pediatric kidney transplant recipients are feasible with high-quality control. Further study will inform whether these signatures are discriminatory and predictive for rejection and infection.</p>

DOI

10.1097/TXD.0000000000001244

Alternate Title

Transplant Direct

PMID

34805493

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