Subsequent kidney transplant after pediatric heart transplant: Prevalence and risk factors.

Pediatric heart failure and transplantation carry associated risks for kidney failure and potential need for kidney transplant following pediatric heart transplantation (KT/pHT). This retrospective, United Network of Organ Sharing study of 10,030 pediatric heart transplants (pHTs) from 1987 to 2020 aimed to determine the incidence of waitlisting for and completion of KT/pHT, risk factors for KT/pHT, and risk factors for nonreceipt of a KT/pHT. Among pHT recipients, 3.4% were waitlisted for KT/pHT (median time of 14 years after pHT). Among those waitlisted, 70% received a KT/pHT, and 18% died on the waitlist at a median time of 0.8 years from KT/pHT waitlisting (median age of 20 years). Moderate-high sensitization at KT/pHT waitlisting (calculated panel reactive antibody, ≥ 20%) was associated with a lower likelihood of KT/pHT (adjusted hazard ratio, 0.67; 95% confidence interval, 0.47-0.95). Waitlisting for heart transplantation simultaneously with kidney transplant (adjusted hazard ratio, 3.73; 95% confidence interval, 2.01-6.92) was associated with increased risk of death on the KT/pHT waitlist. While the prevalence of KT/pHT is low, there is substantial mortality among those waitlisted for KT/pHT. These findings suggest a need to consider novel risk factors for nonreceipt of KT/pHT and death on the waitlist in prioritizing criteria/guidelines for simultaneous heart-kidney transplantation.

Adult and late adolescent complications of pediatric solid organ transplantation.

BACKGROUND: There have been over 51 000 pediatric solid organ transplants since 1988 in the United States alone, leading to a growing population of long-term survivors who face complications of childhood organ failure and long-term immunosuppression. AIMS: This is an educational review of existing literature. RESULTS: Pediatric solid organ transplant recipients are at increased risk for risk for cardiovascular and kidney disease, skin cancers, and growth problems, though the severity of impact may vary by organ type. Pediatric recipients often are able to complete schooling, maintain a job, and form family and social networks in adulthood, though at somewhat lower rates than the general population, but face additional challenges related to neurocognitive deficits, mental health disorders, and discrimination. CONCLUSIONS: Transplant centers and research programs should expand their focus to include long-term well-being. Increased collaboration between pediatric and adult transplant specialists will be necessary to better understand and manage long-term complications.

Kidney transplantation in patients with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a disorder of the mammalian target of the rapamycin (mTOR) pathway associated with the development of multisystem tumors, including renal angiomyolipoma (AML). These renal tumors are benign by nature but locally invasive and carry a risk for the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). The frequency of subsequent renal transplantation in this population is largely uncharacterized, although single-center data suggests that 5%-15% of adult TSC patients are kidney transplant recipients. METHODS: This retrospective cohort study utilized United Network for Organ Sharing (UNOS) data. We included candidates waitlisted between 1987 and 2020 for a first kidney transplant with TSC-associated kidney failure. We utilized descriptive statistics to characterize the frequency of first-time kidney transplant waitlisting and transplantation among persons with TSC and the Fine-Gray subdistribution hazard model to evaluate characteristics associated with progression from waitlist. RESULTS: We identified 200 TSC-associated kidney failure patients within the waitlist cohort. Of these, 12 were pediatric patients. Two-thirds (N = 134) of waitlisted persons were female. One hundred forty patients received a transplant with a median waitlist time of 2 years. Younger age at waitlisting was associated with a greater probability of progressing to transplant (HR 0.98 [95% CI: 0.96-0.99]). 91.8% of kidney transplant recipients survived 1-year post-transplant with a functioning allograft. CONCLUSIONS: The majority of patients with TSC who are waitlisted for a kidney transplant progress onto transplantation with excellent 1-year post transplant patient and allograft survival.

Antibody-mediated rejection in pediatric kidney transplant recipients: A report from the Pediatric Nephrology Research Consortium.

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large-scale pediatric-specific data regarding AMR treatment outcomes. METHODS: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1-18 years at transplant with biopsy-proven AMR between 2009 and 2019 and at least 12 months of follow-up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. RESULTS: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post-transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m2 at AMR diagnosis was associated with a 5.6-fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. CONCLUSIONS: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one-third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure.

Education and employment outcomes in pediatric chronic kidney disease.

As outcomes and survival for children with chronic kidney disease (CKD) have improved over the last 30 years, there is an emerging need to characterize and understand later educational and employment outcomes across the spectrum of pediatric CKD severity-ranging from mild CKD to requirement for dialysis and kidney transplantation. Although large-scale research on the topic of long-term educational and employment outcomes in the pediatric CKD population is relatively scarce, the existing literature does support that children across the spectrum of CKD severity are at risk for education-related difficulties including chronic school absenteeism. These education-related difficulties are compounded by well-described neurocognitive deficits-particularly in the domain of executive functioning-that may potentially perpetuate the risk for academic underachievement. This is particularly concerning given that data from the general pediatric population suggest that childhood academic underachievement is associated with higher likelihood of un-/underemployment in adulthood. This review highlights what is known about educational and employment outcomes among persons with a history of childhood CKD, as well as suggestions for interventions to improve educational outcomes for this population.

Responding to the workforce crisis: consensus recommendations from the Second Workforce Summit of the American Society of Pediatric Nephrology.

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

An Improved Postprocessing Method to Mitigate the Macroscopic Cross-Slice B0 Field Effect on R2* Measurements in the Mouse Brain at 7T.

The MR transverse relaxation rate, R2*, has been widely used to detect iron and myelin content in tissue. However, it is also sensitive to macroscopic B0 inhomogeneities. One approach to correct for the B0 effect is to fit gradient-echo signals with the three-parameter model, a sinc function-weighted monoexponential decay. However, such three-parameter models are subject to increased noise sensitivity. To address this issue, this study presents a two-stage fitting procedure based on the three-parameter model to mitigate the B0 effect and reduce the noise sensitivity of R2* measurement in the mouse brain at 7T. MRI scans were performed on eight healthy mice. The gradient-echo signals were fitted with the two-stage fitting procedure to generate R2corr_t*. The signals were also fitted with the monoexponential and three-parameter models to generate R2nocorr* and R2corr*, respectively. Regions of interest (ROIs), including the corpus callosum, internal capsule, somatosensory cortex, caudo-putamen, thalamus, and lateral ventricle, were selected to evaluate the within-ROI mean and standard deviation (SD) of the R2* measurements. The results showed that the Akaike information criterion of the monoexponential model was significantly reduced by using the three-parameter model in the selected ROIs (p = 0.0039-0.0078). However, the within-ROI SD of R2corr* using the three-parameter model was significantly higher than that of the R2nocorr* in the internal capsule, caudo-putamen, and thalamus regions (p = 0.0039), a consequence partially due to the increased noise sensitivity of the three-parameter model. With the two-stage fitting procedure, the within-ROI SD of R2corr* was significantly reduced by 7.7-30.2% in all ROIs, except for the somatosensory cortex region with a fast in-plane variation of the B0 gradient field (p = 0.0039-0.0078). These results support the utilization of the two-stage fitting procedure to mitigate the B0 effect and reduce noise sensitivity for R2* measurement in the mouse brain.

Post-acute and Chronic Kidney Function Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Initiative.

We investigated the risks of post-acute and chronic adverse kidney outcomes of SARS-CoV-2 infection in the pediatric population via a retrospective cohort study using data from the RECOVER program. We included 1,864,637 children and adolescents under 21 from 19 children's hospitals and health institutions in the US with at least six months of follow-up time between March 2020 and May 2023. We divided the patients into three strata: patients with pre-existing chronic kidney disease (CKD), patients with acute kidney injury (AKI) during the acute phase (within 28 days) of SARS-CoV-2 infection, and patients without pre-existing CKD or AKI. We defined a set of adverse kidney outcomes for each stratum and examined the outcomes within the post-acute and chronic phases after SARS-CoV-2 infection. In each stratum, compared with the non-infected group, patients with COVID-19 had a higher risk of adverse kidney outcomes. For patients without pre-existing CKD, there were increased risks of CKD stage 2+ (HR 1.20; 95% CI: 1.13-1.28) and CKD stage 3+ (HR 1.35; 95% CI: 1.15-1.59) during the post-acute phase (28 days to 365 days) after SARS-CoV-2 infection. Within the post-acute phase of SARS-CoV-2 infection, children and adolescents with pre-existing CKD and those who experienced AKI were at increased risk of progression to a composite outcome defined by at least 50% decline in estimated glomerular filtration rate (eGFR), eGFR <15 mL/min/1.73m2, End Stage Kidney Disease diagnosis, dialysis, or transplant.