Pediatric Transplantation最新文献

Introduction: Machine perfusion (MP) can help expand the donor pool, yet its use in pediatric liver transplantation (LT) has been limited. We aimed to compare the characteristics and outcomes of children undergoing LT with vs. without MP.

Methods: We retrospectively compared children (< 18 years) undergoing first LT with vs. without MP using United Network for Organ Sharing data (01/01/2016-12/31/2024). The MP group was compared to all non-MP and to propensity score matched non-MP LT recipients.

Results: Forty MP LT recipients were compared to 3857 all non-MP and 40 matched non-MP recipients. Compared to all non-MP recipients, MP recipients had a higher laboratory MELD/PELD score (median 16.5 vs. 12.0, p = 0.03) and were more likely to receive split grafts (42.5% vs. 21.6%, p = 0.001) allocated at a national level (65.0% vs. 40.8%, p = 0.007) from older donors (median 16.0 vs. 11.0 years, p < 0.001) with longer organ preservation times (median 15.0 vs. 6.5 h, p < 0.001). Although not statistically different, DCD liver grafts were used in 20.0% of MP LTs compared to 11.1% of all non-MP LTs (p = 0.08). Compared to matched non-MP recipients, MP recipients were more likely to have ascites (47.2% vs. 19.4%, p = 0.02). There was no significant difference regarding patient or graft survival between the MP and all non-MP (p = 0.68 and p = 0.80) or the matched non-MP groups (p = 0.28 and p = 0.14).

Conclusion: MP can support LT in sick pediatric recipients using split grafts, while allowing for prolonged preservation times and national-level allocation at a larger radius, without impacting survival.

Background: As short-term outcomes following pediatric liver transplantation improve, an increasing burden of morbidity arises from chronic graft dysfunction warranting retransplantation. In this single-center retrospective cohort study, we aim to describe outcomes and determine factors that influence morbidity and mortality following liver retransplantation in pediatric recipients.

Methods: Data were collected on patient, and surgical factors which may influence survival and morbidity in all recipients < 18 years of age undergoing liver retransplantation between 2010 and 2024. Retransplants within 21 days were defined as early retransplants. For late retransplants, medical records were additionally reviewed to identify cases transplanted with acute decompensation of liver disease with organ failures. These cases were classified according to EASL-CLIF criteria for acute-on-chronic liver failure (ACLF).

Findings: Forty-four children underwent 52 retransplants with six third grafts and two fourth grafts. Sixteen were early retransplants with 9 (56.33%) due to vascular complications and the remaining primary non-function. Thirty-six were late retransplants with 13 (36.1%) due to chronic rejection and 13 (36.1%) due to biliary complications. Eight (22.2%) late retransplants fulfilled ACLF criteria. Patient survival for all retransplants at 1-, 5- and 10-year was 75% (95% CI: 64.1%-87.7%), 69.1% (95% CI: 57.6%-82.9%), 64.8% (95% CI: 51.9%-80.9%) and graft survival was 70.0% (95% CI: 58%-85.3%), 57% (95% CI: 43%-74.4%), 46% (95% CI: 32%-68.5%) respectively with no significant difference in survival for early versus late retransplants. Factors significantly associated with reduced retransplant survival for late retransplants were preoperative renal replacement therapy (HR: 3.80, 95% CI: 1.09-13.28, p = 0.04), meeting criteria for ACLF (HR: 3.08, 95% CI: 1.14-8.31, p = 0.03), and prolonged warm ischemia time (HR: 1.24, 95% CI: 1.09-1.67, p = 0.04). No significant perioperative factors reducing posttransplant survival were identified for early retransplants.

Conclusion: Children with chronic graft dysfunction are at risk of ACLF which is associated with significant increased posttransplant mortality. Improved disease models are needed for patients with chronic graft dysfunction to better inform decision-making regarding the timing of retransplantation.

Over the last decades, long-term survival after pediatric liver transplantation (LT) has improved substantially, highlighting the importance of long-term graft and recipient outcomes. Metabolic syndrome, a combination of components associated with increased cardiovascular risk, is a well-defined concept in the general adult population. The same components can be present after LT leading to post-transplant metabolic syndrome (PTMS). In children, PTMS is estimated to be prevalent in around 14%-20% of LT recipients. However, a univocal definition is lacking as well as consensus on specific cut-off values for the different components. The latter comprise: low HDL-cholesterol, high triglycerides (both falling under the heading of "dyslipidemia"), hypertension, impaired fasting glucose and/or impaired glucose tolerance, and (abdominal) obesity. Although most studies have a retrospective or cross-sectional nature and are of relatively small sample size, there seems to be an accumulation of risk factors in the first years after transplantation, declining thereafter and rising again in the long term. Sustained exposure to immunosuppression is identified as a major contributor, as well as accumulating general cardiometabolic risk factors throughout life.

Background: Health administrative datasets have the potential to provide valuable insights into pediatric solid organ transplantation; however, validation is necessary to ensure their accuracy. This study aimed to assess the validity of administrative data by comparing it to direct transplant records from a major pediatric transplant center in Ontario, Canada (1991-2011).

Methods: Using linked administrative healthcare databases, we conducted a retrospective analysis to evaluate the validity of physician billing claims and hospital diagnostic and procedural codes in identifying pediatric solid organ transplants. Sensitivity and positive predictive value (PPV) were calculated for various algorithms.

Results: During the study period, a total of 347 kidney, 250 liver, 200 heart, and 28 lung transplants were performed. The best algorithm for identifying these transplants utilized hospital procedural codes from the Canadian Institute for Health Information Discharge Abstract Database. Compared to transplant center records, these codes demonstrated a sensitivity of 91% (95% CI: 89-93) and PPV of 93% (95% CI: 91-95) when including all organ types, and performed similarly well when evaluating individual organ types.

Conclusion: This study is the first to validate administrative data for identifying pediatric solid organ transplant recipients, demonstrating the reliability of procedural codes for population-level health research in this domain.

Proteinuria is a relatively frequent complication in both adults and children after kidney transplantation (40%-80%). It is usually mild and predominantly of tubular origin and is caused mainly by rejection, mTOR inhibitors, or hypertension; however, proteinuria could also be in the nephrotic range and of glomerular origin if caused by the recurrence of idiopathic FSGS or rejection. Proteinuria is a risk factor impacting graft and patient survival in adults and graft survival in children. Proteinuria should be assessed by protein/creatinine ratio regularly in pediatric kidney transplant recipients. In children with idiopathic FSGS, proteinuria should be assessed daily during the first 2-3 weeks post-transplant to enable prompt diagnosis of recurrence. The etiology of proteinuria should be identified (recurrence, rejection, mTOR-inhibitors, hypertension, etc.). If no apparent cause is found, a graft biopsy should be considered. Antiproteinuric therapy is primarily focused on treating the causes of the proteinuria, and this is usually done using Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs). The long-term follow-up goal should be normalization of proteinuria with a protein/creatinine ratio < 20 mg/mmol (200 mg/g). Because of the role elevated blood pressure may play in exacerbating proteinuria, antihypertensive medications should be used in those who are resistant to initial antiproteinuric therapy to achieve lower BP.

Background: Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder that leads to systemic oxalosis and end-stage renal disease (ESRD). Before the advent of siRNA therapy, liver transplantation, often combined with kidney transplantation, was the only definitive treatment.

Methods: We conducted a retrospective review of eight pediatric patients with PH1 who underwent liver transplantation at a single tertiary care institution between 1998 and 2018. Clinical records were reviewed to extract data on transplant strategy, timing and modality of dialysis, surgical technique, and long-term outcomes. Histopathological and imaging data were used to assess systemic oxalate deposition.

Results: Five patients underwent sequential liver-kidney transplantation (seqLKT), one received preemptive liver transplantation, and two received kidney transplantation prior to PH1 diagnosis. To reduce systemic oxalate burden, seqLKT patients received intensive dialysis bridging. Following an early case of hepatic artery thrombosis, arterial conduit reconstruction to the aorta was employed in subsequent cases to optimize hepatic inflow. Oxalate deposition in arterial walls, retina, or bone was documented in three patients. At a median follow-up of 7.5 years, seven of eight patients were alive with stable hepatic and renal graft function.

Conclusions: This case series illustrates the surgical complexity and multidisciplinary coordination required in pediatric PH1 management and supports the role of seqLKT with conduit-based hepatic artery reconstruction and intensive dialysis bridging as effective approaches in selected patients, particularly in settings without access to gene-targeted therapy.

Background: Tacrolimus is the maintenance immunosuppression of choice in pediatric liver transplant (LT) recipients. However, in selective cases, sirolimus is used as an alternative immunosuppressive treatment. We aimed to review a single centre's experience of using sirolimus as an alternative to tacrolimus in pediatric LT recipients.

Methods: Single centre retrospective study of pediatric LT recipients who were started on sirolimus as an alternative immunosuppressant to tacrolimus. Children (< 16 years) who were started on sirolimus between May 2000 and May 2024 were included in the study.

Results: A total of 19 children were started on sirolimus following LT and followed up for a median of 4 years (range 0.4-12.8). Post-transplant lymphoproliferative disorder (PTLD) was the most common reason for tacrolimus discontinuation and conversion to sirolimus (n = 14), followed by tacrolimus-related adverse effects (n = 4) and disease recurrence (n = 1). There were no cases of PTLD recurrence or biopsy-confirmed rejection whilst on sirolimus. Proteinuria and hyperlipidaemia were the most common sirolimus side effects observed. Eighteen children remain on sirolimus to date, and none required discontinuation from side effects. In those with PTLD, 4 episodes of rejection occurred between the period of tacrolimus discontinuation and starting sirolimus (median immunosuppression-free time of 5 months), with one child requiring regrafting due to chronic rejection.

Conclusion: The experience from our centre demonstrates sirolimus to be a safe and effective alternative to tacrolimus in a selected population of pediatric LT recipients. Further research with a larger sample size is required to confirm these findings and evaluate the long-term safety of sirolimus in this population.

Background: End-stage renal disease (ESRD) is a critical global health concern, with kidney transplantation being the preferred treatment for children with stage 5 chronic kidney disease. However, ABO-incompatibility (ABOi) poses a major barrier to successful transplantation. While advances in antibody removal techniques, including immunoadsorption (IA), have enabled ABOi kidney transplantation, cost remains a significant challenge, especially in low-resource settings. Most available data focus on adults, with limited pediatric reports, particularly using reusable IA columns.

Case presentation: We report the case of a 7-year-old girl who underwent ABOi kidney transplantation from her mother, despite an exceptionally high pretransplant anti-B IgG antibody titer of 1:1 024. She received a single dose of Rituximab (200 mg) 14 days pretransplant, followed by two IA sessions using a reusable Vitrosorb IA column. The first session reduced titers to 1:16, but a rebound increase to 1:128 necessitated a second session, bringing titers down to 1:8. A final plasmapheresis session stabilized titers before transplantation. The surgery was uneventful, and post-transplant antibody levels remained controlled. The patient demonstrated good graft function and was discharged in stable condition.

Discussion & conclusion: This is the highest reported pretransplant titer (1:1 024) in a pediatric ABOi kidney transplant case. The use of a reusable Vitrosorb IA column proved both effective and cost-efficient, making it a viable option in resource-limited settings. Our findings suggest that IA reuse is safe, reduces financial burden, and warrants further investigation for broader clinical application.

Background: Early studies evaluating steroid-minimization (SM) employed immunosuppression that is not representative of the modern era of immunosuppression. We hypothesized that current SM-based immunosuppression protocols offer unique advantages for pediatric kidney transplant recipients (pKTR) without compromising allograft and patient outcomes.

Methods: This is a retrospective study of 3263 pKTR between 2000 and 2019 from the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS). Study participants were grouped as SM and steroid based (SB) based on corticosteroids use at 30 days post-transplant. Primary outcomes of interest were allograft function and survival. Secondary outcomes included linear growth, obesity and hypertension.

Results: A SB regimen was used in 2312 (70.9%) and SM in 951 (29.1%). Comparison of the allograft function showed that SM was associated with a significantly higher estimated glomerular filtration rate (eGFR) at 1, 2, and 3 years post-transplant compared to SB. Kaplan-Meier curves showed that SM was associated with significantly less allograft loss (p = 0.01) compared to SB while there was no significant difference in allograft survival when stratified by induction and steroid regimen (p = 0.49). Multivariate Cox regression showed that the SB regimen was not associated with improved graft survival (hazard ratio 1.38 [0.89-2.16]; p = 0.15). Secondary outcome analysis showed significantly better linear growth and less obesity and hypertension in SM compared to SB.

Conclusions: SM immunosuppression was not associated with decreased allograft rejection, function or survival, and was associated with a reduced risk of secondary complications. In patients receiving contemporary, tacrolimus-based maintenance immunosuppression, a SM regimen may be preferred.

Objective: To describe an exceedingly rare vascular anatomical variant of the splenic artery arising from the superior mesenteric artery (SMA), termed a splenomesenteric trunk, with angiographic imaging in a pediatric patient.

Methods: Case review of a 6 year-old boy, status post liver transplantation for biliary atresia, who presented with ongoing hematemesis, melena, portal hypertension and chronic thrombocytopenia from hypersplenism. He underwent portal venous stenting, and we decided to perform a partial splenic embolization to reduce portal pressure and improve platelet counts. CT and angiographic imaging findings are presented, with literature correlation.

Results: CT 3D and DSA demonstrated the absence of the splenic artery on injection of the celiac trunk. Selective SMA angiography revealed a variant origin of the splenic artery from the SMA, with normal caliber and no aneurysm or stenosis.

Conclusion: Recognition of this rare vascular variant is essential to avoid procedural complications. This represents, to our knowledge, the first angiographically documented case of a splenomesenteric trunk in a pediatric patient.