Pediatric Transplantation最新文献

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.

Background: Resolution of BK viremia is almost universally required before kidney transplant. Unfortunately, proven anti-BK viral therapies are limited. The Seraph 100 mimics the action of the natural glycocalyx, which binds pathogens via heparin sulfate proteoglycans. In this case report, we describe the use of this filter to facilitate the clearance of BK viremia.

Methods: Our patient was a 14-year-old cardiac transplant recipient secondary to familial dilated cardiomyopathy. She developed BK nephropathy resulting in end stage kidney disease (ESKD). After failed medical management and immunoreduction over 4 years, the Seraph 100 Microbind Affinity Blood Filter was utilized extracorporeally in line with continuous renal replacement therapy (CRRT) for 48 h to eliminate detectable BK viral replication.

Results: The patient's BK titers initially increased negligibly but cleared within 2 months of Seraph 100 treatment, and she successfully underwent kidney transplantation without recurrence of BK viremia. There were no adverse events other than one episode of emesis at the initiation of CRRT.

Conclusion: Our case provides proof of concept and feasibility for studying the Seraph 100 as a potential therapeutic option for the clearance of BK viral titers, especially in ESKD patients who already have dialysis access.

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: Liver transplant (LT) waitlist mortality occurs in 10% of children; innovative strategies to expand access to LT can be lifesaving.

Methods: Outcomes of ABO incompatible (ABOi) LT performed between 1999 and 2023 at a high-volume center were compared to ABO compatible (ABOc) LT.

Results: 25 ABOi LT were performed among 270 LT; 72% were listed with status 1/1A/1B or a median pediatric end-stage liver disease/model for end-stage liver disease of 40 (IQR 32,41). Time on the waitlist for ABOi recipients was shorter (median 11 days [IQR 4,46]) compared to ABOc (113 days [IQR 39,252], p < 0.001). ABOi graft types were 64% technical variants (including 2 living donor grafts) and 36% whole; 52% received a duct-duct biliary anastomosis. There were no statistically significant differences in 1/5/10-year patient survival [ABOi: 87,87,87% vs. ABOc: 96,94,89%, p = 0.6] or graft survival [ABOi: 87,82,82% vs. ABOc: 92,86,80%, p = 0.9]. When compared to ABOc, there were no statistically significant differences in vascular complications, bile leaks, or acute T-cell-mediated rejection with ABOi LT. Biliary strictures were diagnosed in 43% of ABOi LT and more frequently than in ABOc (20%, p = 0.0495).

Conclusions: ABOi LT can offer children on the waitlist a survival advantage through shorter waiting time. ABOi LT can be performed safely with a low rate of vascular complications similar to ABOc LT.

Background: Post-transplant lymphoproliferative disorders (PTLD) may significantly impair outcomes in children after solid organ transplantation (SOT). Diagnosis and treatment may be challenging. We analyze a representative pediatric liver transplant (LT) cohort in light of these challenges.

Methods: Pediatric LT recipients monitored by the Swiss Pediatric Liver Center from 2009 to 2021 with a suspicion of Epstein-Barr virus (EBV) driven PTLD were included. All cases were retrospectively reviewed using the World Health Organization (WHO) 2022 classification criteria for Pediatric Tumors. Two groups were defined: (1) histologically confirmed PTLD, and (2) 'indeterminate PTLD' if criteria were not entirely met.

Results: During the inclusion period, 111 patients underwent LT. Histology review confirmed PTLD in 13 patients (11.7%) while 3 patients were included in the 'indeterminate' group. The most common subtype was non-destructive PTLD (6/13), followed by monomorphic (4/13) and polymorphic PTLD (3/13). Hypermetabolism on whole body (¹⁸F) fluorodeoxyglucose PET/CT helped define adequate biopsy location in 11/13 patients. Three patients with monomorphic PTLD also showed low-grade PTLD subtypes in other biopsy sites. Nine patients received mTOR inhibitors after diagnosis, either as monotherapy or in combination with calcineurin inhibitors, without major side effects.

Conclusions: The detailed analysis of our series of pediatric LT patients with PTLD allowed for the development of a diagnostic and management algorithm, now applied at our institution. Spatial and temporal heterogeneity argues in favor of multiple and, if necessary, repeated biopsies at different sites.

Background: Reports on bilateral simultaneous native nephrectomies in the pediatric population are lacking. This study evaluates indications and outcomes of a tertiary care pediatric hospital's single center experience with bilateral simultaneous native nephrectomies over 15 years.

Methods: A retrospective chart review of pediatric patients (< 21 years old) who underwent bilateral simultaneous native nephrectomy from January 1, 2009, to August 1, 2024, at a single institution was performed for surgical indications, approach, and outcomes.

Results: Ten patients were identified. Mean age at bilateral simultaneous nephrectomy was 9.6 years (range 14 months-19 years). Surgical indications included hypertensive crisis in four, nephrotic syndrome in three, Polycythemia Vera in one, recurrent urinary tract infections (UTI) in one, and significant hydroureteronephrosis in one patients. Prior to nephrectomy, six patients were on hemodialysis, two patients were on peritoneal dialysis (PD), and two patients were not on any form of dialysis. Of the 10 patients, four underwent surgery during an inpatient admission for an acute exacerbation of the listed indication. Three cases were done robotically (transperitoneal), and seven were performed open. Both patients on PD preoperatively underwent open retroperitoneal surgery and were able to restart PD on postoperative day 1. There was one complication in a patient with recurrent UTIs who developed an intra-abdominal abscess, requiring percutaneous drainage.

Conclusions: Bilateral simultaneous native nephrectomy is a safe and effective way to manage conditions associated with end-stage renal disease in pediatric patients. In our experience, this can be done by an open or minimally invasive approach.

Background: Partial heart transplantation (PHT) is a new type of transplant that delivers growing heart valve implants for children. However, the acceptable ischemia time for PHTs remains unexplored. Therefore, the ischemia time for PHTs is empirically limited to orthotopic heart transplant (OHT) ischemia time of 4-6 h because the valves contained in OHTs are known to grow. This limits the distance from where PHT grafts can be procured. Without longer procurement distances, children who need PHT must wait a long time for suitable donor hearts. We previously demonstrated that PHTs remain viable for an ischemia time of 48 h in a rat model. Here we expand on this work in a porcine model.

Methods: Porcine pulmonary valve (PV) and aortic valve (AV) leaflets were preserved in DMEM culture medium, Belzer UW, Unisol, or HTK solution (n = 6/group) at 4°C. At preset intervals, the cellular viability was measured using the alamarBlue assay. The valves were also analyzed with flow cytometry and histology.

Results: While the metabolic activity of the valves slowly decreased over time, there was significant cellular viability for up to 21 days of cold preservation with Belzer UW solution. Flow cytometry and histology further corroborated the results, showing cellular preservation at 7 days of ischemia time.

Conclusions: OHT preservation is limited to only 4-6 h because longer ischemia times are associated with primary graft dysfunction from reduced contractility of ventricular myocardial cells. In contrast, PHTs spare the native ventricles. Our results indicate that PHT grafts remain viable much longer than OHT grafts. In vivo data are needed to verify that PHT grafts can grow and function after this significantly increased ischemic time.