Pediatric Transplantation最新文献

Introduction: Heart transplantation is the definitive treatment for infants and children with nine advanced stages of congenital heart failure. This study presents the experiences of a single medical center regarding pediatric heart transplants conducted over a decade.

Methods: Baseline characteristics of recipients and donors of pediatric heart transplant patients from 2012 to 2021 were recorded. Post-transplant complications and survival rates were assessed during a median follow-up period of 2 years.

Results: The study, which spanned a decade and included 225 transplants, revealed several key findings. The mean age of recipients was 10.8 years, with a majority being boys. The most common diagnoses were dilated cardiomyopathy (83.6%) and restrictive cardiomyopathy (8.0%). Donors, with a mean age of 21.4 years, were predominantly male. The primary causes of donor death were head trauma/motor vehicle accidents (56.9%). Notably, post-transplant complications included Renal failure requiring dialysis (15.7%), Central Nervous System (16.9%), Cytomegalovirus infections (24.9%), and Epstein-Barr virus infections (21.8%). During the follow-up, 48 deaths were recorded, yielding a crude mortality rate of 7.4 per 100 person-years. The 1-year, 3-year, and 5-year survival rates, which were 85.7%, 79.7%, and 73.9%, respectively, demonstrate the significant progress in pediatric heart transplant outcomes over the past decade.

Conclusion: Pediatric heart transplant outcomes have improved over the past decade, although challenges remain. Significant risk factors for mortality include donor age, male donor gender, and 28 Rituximab treatment. Strategies to mitigate these risks could enhance survival rates post-transplant.

Background: Parents of pediatric heart transplant (HTx) recipients have a unique perspective on the challenges associated with the transition into adult care networks. We sought to assess parental perceptions of the challenges pediatric HTx recipients face daily and parental concerns around the transition from pediatric care networks.

Methods: A 15-item online survey was developed in partnership with parent-stakeholders and administered to parents of pediatric HTx recipients in September 2023. Closed and open-ended questions assessed (1) the patients' diagnosis, age at diagnosis, and age at transplant, (2) parents' daily concerns about their child's well-being, (3) parents' overall concerns about their child's well-being as they transition into adulthood, (4) parents' perceptions of their child's quality-of-life (QoL) and health, and (5) parents' demographic characteristics.

Results: Eighty-six parents completed the survey. On a scale of 1 (worst) to 10 (best), 75% of parents rated their child's overall QoL at 8 or higher and 76% rated their child's health-related QoL at 8 or higher. Parents' daily concerns about their child's well-being included infectious diseases, health behaviors and care management, transplant-related concerns, socialization and education, mental health, and care coordination. Concerns related to the transition into adulthood included health behaviors and self-management, life satisfaction, finances, family, transplant-related concerns, and care coordination.

Conclusions: Although parents of pediatric HTx recipients reported mostly positive QoL outcomes, they have concerns related to care management, life satisfaction, and healthcare access as their children transition into adulthood. Comprehensive transition-specific interventions and guidelines are needed to support families during this high-risk period.

Background: Renal allograft compartment syndrome (RACS) represents a rare and potentially underdiagnosed cause of allograft dysfunction, typically occurring in the immediate post-transplant period. However, delayed-onset RACS remains underrecognized.

Methods: We present a case of a 14.5-year-old girl with nephronophthisis, who received a kidney transplant from her father and who was diagnosed with late-onset renal allograft compartment syndrome on post-transplant day 20.

Results: In the post-transplant follow-up of this patient, the serum creatinine level increased from the 2nd day. On day 5, surgical re-evaluation was performed as she did not respond to acute rejection therapy with prednisolone, anti-human T-lymphocyte immunoglobulin, and plasmapheresis. Although macroscopic examination of the allograft did not reveal any abnormalities, serum creatinine levels rapidly returned to normal after surgery. However, on the 20th day, serum creatinine started to rise again. Calcineurin toxicity and infectious causes have been ruled out. She received treatment with immunoadsorption and intravenous immunoglobulin as the second biopsy showed glomerulitis and tubulitis. Despite these treatments, the serum creatinine level increased to 6 mg/dL, and she was reassessed surgically. Although the allograft appeared normal, there was edema in the surrounding tissue. Serum creatinine levels returned to normal (0.9 mg/dL) spontaneously after surgery. So, she was diagnosed with late-onset renal allograft compartment syndrome due to the edema surrounding the allograft and improvement observed in serum creatinine levels after fascia opening.

Conclusions: RACS should be considered beyond the immediate post-transplant period, particularly when standard interventions fail to improve graft function. Surgical exploration remains a critical diagnostic and therapeutic tool in such cases.

Background: Inborn errors of metabolism (IEMs) are inherited diseases causing significant morbidity and mortality, particularly in childhood. Liver transplantation (LT) can be curative or partially effective for these diseases. LT for IEMs has increased, making IEMs the second most common reason for pediatric LT after biliary atresia.

Patients and methods: Between 2001 and 2023, 50 pediatric patients with IEMs underwent LT at Başkent University, Ankara Hospital. Data collected retrospectively included diagnosis, gender, age of diagnosis, age of LT, LT indication, donor data, graft type, rejection episodes, post-transplant complications, and clinical findings of the IEMs before and after LT. Treatment methods, follow-up duration, and survival time were also recorded.

Results: Of the 332 pediatric LT patients, 50 (15.1%) had IEMs, with three requiring re-transplantations. Diagnoses included glycogen storage diseases (n = 11), tyrosinemia type 1 (n = 10), primary hyperoxaluria (n = 6), urea cycle disorders (n = 6), homozygous familial hypercholesterolemia (n = 4), propionic acidemia (n = 4), deoxyguanosine kinase deficiency (n = 3), maple syrup urine disease (n = 2), methylmalonic acidemia (n = 1), Niemann-Pick disease type B (n = 1), alkaptonuria with unknown neonatal cholestasis (n = 1), and bile acid synthesis disorder (n = 1). The parental consanguinity rate was 74%. Living-related donors provided organs for 48 (90.5%) patients. The mean age at LT was 75.3 ± 8.2 months (range: 5-218), with a follow-up period of 82.1 ± 10.2 months (range:1 day-229 months). Survival rates at 1, 5, 10, and 15 years were 83.7%, 81%, 81%, and 70.9%, respectively.

Conclusion: LT is an effective solution for children with IEM causing chronic organ failure and difficult to manage with medical treatment, showing a good long-term prognosis.

Aim: Liver transplantation (LT) is a well-accepted treatment for primary sclerosing cholangitis (PSC) with generally good outcomes, although recurrent PSC (rPSC) poses significant challenges. This study aimed to describe patient characteristics and identify potential risk factors of rPSC in pediatric LT recipients.

Methods: This retrospective study analyzed 13 pediatric patients who underwent LT for PSC at a single center. Patient characteristics, risk factors, and outcomes were compared between those with and without rPSC.

Results: The median age at PSC diagnosis was 5.2 years and at LT, 15.4 years. Inflammatory bowel disease (IBD) was present in 12 patients (92.3%), and four (30.7%) had overlapping autoimmune hepatitis (AIH) before LT. Two patients received grafts from living-related donors, and 11 from deceased donors. During a median follow-up of 53 months, 4 of the 13 patients (30.7%) developed rPSC at a median of 48.9 months post-LT. Patients with rPSC tend to be younger at PSC diagnosis. All rPSC cases were associated with IBD, and half had AIH overlap, though the frequency difference was not significant. Acute cellular rejection (ACR) was universal in rPSC patients (100%) compared to nonrecurrent cases (33.3%, p = 0.07). One case of rPSC developed pulmonary hypertension following rPSC and succumbed to PH crisis, resulting in a 5-year patient survival rate of 82%.

Conclusions: The recurrence rate was high in pediatric patients with PSC. The observed association with immune-activating conditions raises the possibility of utilizing immunologic interventions to prevent rPSC, although further prospective studies are warranted to clarify the underlying mechanisms.

Background: BK Polyoma virus (BKV) can lead to significant renal complications in immunocompromised individuals. While commonly observed in kidney transplant recipients, its occurrence in non-renal solid organ transplant (NRSOT) recipients remains rare. The mainstay of treatment for BKV nephropathy in these patients involves careful reduction of immunosuppression.

Summary: In this report, we present a unique case of end-stage renal disease due to refractory BKV nephropathy in a pediatric heart transplant patient. The patient was treated with bilateral native nephrectomy to eliminate the viral reservoir with clearance of her BK viremia. This led to a six-month period of viral clearance, allowing for subsequent living donor kidney transplantation (LDKT).

Conclusion: BKV nephropathy is a rare entity in NRSOT patients. This case highlights the successful management of refractory BKV nephropathy in a pediatric heart transplant recipient through bilateral native nephrectomy, leading to an extended period of viral clearance and subsequent LDKT. Further studies are needed to explore the broader applicability of this approach in NRSOT recipients.

Background: Pediatric kidney transplantation requires complex multidisciplinary coordination. The contributions of pharmacotherapeutic aspects to this practice have been of fundamental importance, even in low- and middle-income countries (LMIC).

Methods: We conducted a quasi-systematic review of the PubMed and Google Scholar databases from inception to July 2024 using Medical Subject Headings and keywords relevant to Therapeutic Drug Monitoring (TDM) and Model-Based Precision Dosing (MIPD). The quality of the articles and data collected were appraised using the appropriate critical appraisal tools and was synthesized qualitatively.

Results: TDM and the analyses and interpretations associated with pharmacometric aspects, specifically clinical pharmacokinetics, have led to the use of modern strategies such as MIPD. These strategies allow for individually adjusted drug dosages to be optimized, making them more effective and safer for many immunosuppressants, antibiotics, antivirals, antifungals, antiepileptics, antineoplastics, and antiarrhythmics, among others. Several points of interest associated with improving the implementation and practice of TDM-MIPD, particularly challenging in LMICs, include the availability and adequate management of economic resources (such as software and laboratory supplies), the development of collaborative work with other institutions (including foreign ones), the possibility of consolidating independent management not depending on other clinical services, the need to train and maintain highly skilled professional staff for clinical and research purposes, and the establishment and maintenance of specialized educational programs.

Conclusion: Throughout the world, but especially in LMICs, there is a need to intensify strategies that allow for the more widespread application of TDM-MIPD to improve pharmacotherapeutic care for this highly vulnerable patient population.

Background: Biliary strictures (BS) remain a challenge in pediatric liver transplant (LT). Achievement of the "Optimal Biliary Outcome" (OBO), stricture resolution without recurrence or surgery is the goal. We analyzed cost associated with different management.

Methods: Society of Pediatric LT (SPLIT) data were matched with Pediatric Health Information System (PHIS) data by dates of birth and transplant, center and sex. SPLIT data were used to identify LT recipients (2011-2016) with BS. Procedure and admissions costs from PHIS were inflation-adjusted to 2022. Sub-analyses evaluated costs associated with achieving OBO.

Results: Optimal biliary outcome was achieved in 42% of 77 participants following a median of 4 procedures and 2 inpatient nights compared to a median of 7 procedures and 4 nights in those without OBO (p < 0.001). BS management was lower in participants who achieved OBO versus who did not achieve OBO (p = 0.004). Significant center variation in cost was observed (p < 0.001). Biliary strictures diagnosed earlier post-PLT were associated with lower costs per patient (p = 0.049), while those who underwent surgical biliary revision did not incur higher costs per patient (p = 0.17). In participants who did not achieve OBO and underwent ≥ 6 PTC procedures tended to incur much higher costs compared to those who underwent ≤ 5 PTC procedures, regardless of surgical biliary revision (p = 0.08).

Conclusions: Biliary stricture management costs were highest in patients requiring treatment for recurrence or surgical biliary revision and lowest earlier post-transplant, suggesting that more aggressive management upfront may optimize costs. Future work will explore practice variation and cost-effective strategies to achieve OBO.

Introduction: Primary hyperoxaluria type 1 (PH1) is a very rare inherited metabolic disorder characterized by excessive oxalate production due to mutation variants in the alanine-glyoxylate aminotransferase gene (AGXT). Approximately 4% of PH1 cases are diagnosed after kidney transplantation. Most post-transplant recurrences of PH1 are associated with poor graft outcomes. Lumasiran, a novel RNA interference (RNAi) therapeutic for PH1, was recently discovered with promising results.

Methods: This report describes a pediatric case of PH1 diagnosed post-kidney transplantation with graft dysfunction who was treated with extensive hemodialysis and lumasiran as rescue therapy.

Results: Patient was able to stop hemodialysis with the improvement of her kidney function and plasma oxalate after the fourth dose of lumasiran.

Conclusion: This case underscores the importance of maintaining a high index of suspicion for PH1 in patients with congenital anomalies of the kidney and urinary tract (CAKUT) or unexplained end-stage kidney disease (ESKD) cases, even post-transplantation. It also demonstrates the potential efficacy of lumasiran in managing PH1 post-transplantation when combined with intensive hemodialysis and supportive care. However, more studies with prolonged follow-up periods are necessary to establish the long-term efficacy and safety of lumasiran in the treatment of PH1 without the requirement for liver transplantation.