Pediatric Transplantation最新文献

Background: The majority of patients who undergo ventricular assist device (VAD) implant in childhood survive to adulthood. This study examined the neurodevelopmental trajectory post VAD and determined factors associated with non-optimal outcome.

Methods: Patients implanted with a VAD aged < 6 years between 01/2006 and 12/2020, who underwent assessment at 4.5-7-years of age (and > 6 months post decannulation) with the Complex Pediatric Therapies Follow-up Program were included in a prospective-inception-cohort study. Optimal neurodevelopmental outcome was defined as scores of ≥ 80 on the Wechsler Preschool and Primary Scales of Intelligence, the Beery-Buktenica Developmental Test of Visual-Motor Integration and on the Adaptive Behavior Assessment System, in the absence of cerebral palsy, permanent hearing loss, visual impairment, or seizure disorder. Firth multiple regression analysis was used to determine independent factors associated with non-optimal outcome.

Results: A total of 74 patients underwent VAD implant at age < 6 years with neurodevelopmental assessments available for 48/51 patients who survived to testing. Median age at implant was 0.63 years (IQR 0.20, 2.74), 37.5% were female and 39.6% had congenital heart disease. Optimal outcome occurred in 33% of patients. Optimal outcome was associated with female sex [OR 8.03 (95% CI 1.69-56.64) p = 0.007] and implant between 2015 and 2020 [OR 6.59 (95% CI 1.42-42.62) p = 0.016]. Neurological insult sustained pre-post-VAD [OR 0.10 (95% CI 0.01-0.63) p = 0.01] was associated with a non-optimal outcome.

Conclusion: Optimal outcome was present in one-third of patients. Protective factors were female sex and implant between 2015 and 2020. Neurological insult was associated with a non-optimal outcome.

Background: Variability in tacrolimus levels, measured with the Medication Level Variability Index (MLVI), and intrapatient variability (IPV) may be associated with graft outcomes in solid organ transplant recipients. However, the optimal method for measuring tacrolimus variability, the optimal timing for measurement, and intervention thresholds for pediatric kidney transplant recipients remain uncertain.

Methods: Our retrospective study included 149 pediatric kidney transplant recipients who received tacrolimus for maintenance immunosuppression. MLVI and IPV were assessed across 3 post-transplant intervals: 2-week to 3-month; 3- to 6-month; and 6- to 12-month. Associations between MLVI or IPV and graft outcomes were analyzed using landmark survival analysis, adjusting for age at transplant, donor type, and transplant year. We used survival trees to identify optimal thresholds.

Results: MLVI during 2-week to 3-month (aHR: 1.65; 95% CI: 1.08-2.52; p = 0.02) and 6-12-month intervals (aHR: 3.82; 95% CI: 1.39-10.5; p = 0.009) post-transplant was significantly associated with the risk of graft failure. Similarly, IPV during 2-week to 3-month (aHR: 1.63; 95% CI: 1.03-2.59; p = 0.04) and 6 to 12-month intervals (aHR: 2.22; 95% CI: 1.05-4.71; p = 0.04) was significantly associated with the risk of graft failure. IPV during a 2-week to 3-month interval was significantly associated with de novo donor-specific antibody (dnDSA) development (aHR: 1.38; 95% CI: 1.07-1.78; p = 0.02). We observed no significant associations between the 3- and 6-month interval and graft failure. Neither MLVI nor IPV during any interval predicted acute rejection.

Conclusions: IPV during the first 3 months was associated with dnDSA development. Both MLVI and IPV during the first 3 months and at the 6- to 12-month interval post-transplant were associated with increased risk of graft failure.

Background: This pilot study evaluated the feasibility of integrating an immunosuppressant area under the concentration-time curve (AUC) monitoring for tacrolimus and mycophenolic acid (MPA) into pediatric kidney transplantation care.

Methods: Dedicated test codes, an AUC requisition form, and a coordinated laboratory sampling process were established for tacrolimus and MPA AUC. AUC was calculated using the ISBA 3.0 Bayesian pharmacokinetic platform. AUC results were correlated with doses, trough concentrations (C₀), 3 h post-dose concentrations (C_3h), and clinical outcomes.

Results: The AUC protocol was successfully integrated into the routine clinical workflow. Tacrolimus AUC showed correlations with dose (r = 0.85) and C₀ (r = 0.82); similarly, MPA AUC showed correlation with dose (r = 0.61) and C_3h (r = 0.65). Of the 21 Tacrolimus AUC measurements, 76% were within the target range, and 24% were below the range. For MPA AUC measurements, 65% (13/20) were within the target range, 5% (1/20) were below the range, and 30% (6/20) were above the range. Following individual AUC measurements, the tacrolimus dose was adjusted after 43% (9/21) of measurements, and the mycophenolate mofetil (MMF) dose was adjusted after 50% (10/20) of measurements.

Conclusion: This AUC pilot study demonstrated the feasibility of integrating AUC-guided monitoring into the routine management of pediatric kidney transplant recipients.

Background: Nutritional status influences outcomes after pediatric kidney transplantation. While obesity is associated with delayed graft function (DGF) in adults, prior pediatric literature has reported inconsistent associations between body mass index (BMI) and early graft function, leaving uncertainty about whether higher BMI contributes to early dysfunction in children.

Methods: We studied pediatric kidney-only recipients in the Organ Procurement and Transplantation Network (OPTN) registry. Exclusions were age < 2 years, prior or multi-organ transplants, or missing BMI, dialysis, or hospital length of stay (HLOS) data. BMI was classified using Centers for Disease Control and Prevention growth charts. Outcomes were DGF, slow graft function (SGF), and HLOS. Trend testing evaluated ordered associations across BMI categories. Logistic regression estimated adjusted associations between BMI category and DGF and SGF, and linear regression was used for HLOS.

Results: Among 9098 recipients, the incidence of DGF increased progressively across BMI groups, from 3.9% in underweight to 5.9% in obese recipients (trend p = 0.016). In adjusted models, each higher BMI category was associated with greater odds of DGF (OR 1.16, 95% CI 1.07-1.27, p < 0.001) and SGF (OR 1.20, 95% CI 1.06-1.35, p = 0.004). HLOS was modestly longer in higher-BMI groups (median 9 vs. 8 days; p < 0.001).

Conclusion: Higher BMI is associated with modest differences in early graft dysfunction in pediatric kidney transplantation. Trend analyses demonstrate a graded association between BMI and DGF and SGF, with small absolute differences across BMI categories.

Background: Focal segmental glomerulosclerosis (FSGS), which can be caused by many etiologies, is one of the major causes of nephrotic syndrome and end-stage kidney disease. Multiple etiologies, including glomerular hyperperfusion, can cause secondary FSGS. Unilateral renal artery stenosis can lead to FSGS of the contralateral native kidney, but it is not well demonstrated whether transplant renal artery stenosis can cause a similar change in a single transplanted kidney.

Case presentation: A female underwent kidney transplantation at the age of 17 on January 14, 2020. Her renal function remained stable until 25 months later, when the patient presented with hypertension and elevated serum creatinine (SCr), with an unremarkable urine test. Ultrasound and computed tomography angiography (CTA) revealed stenosis at the initial segment of the main transplant renal artery. After percutaneous transluminal angioplasty of the main transplant renal artery, her SCr and blood pressure recovered. 5 months later, hypertension recurred with moderate proteinuria (2.5 g/d). An allograft biopsy showed a remarkable cellular FSGS lesion. Due to the absence of glomeruli in the electronic microscope sample, a second biopsy was performed a month later. Unexpectedly, no FSGS, except for very mild glomerular hypoperfusion and remarkably enlarged juxtaglomerular apparatus, was found. Hemodynamic abnormality in the kidney was suspected as the two biopsy sites were from the lower pole and upper pole, respectively. The donor kidney had an accessory renal artery on a common aortic patch with the main renal artery. Doppler ultrasonography confirmed two different hemodynamic areas in the kidney. Transplant renal artery stenosis of the main artery induced an FSGS lesion in the region dominated by the accessory artery. Endovascular stenting was performed, and her proteinuria turned negative, with SCr recovering only 3 days later. The patient had long-term follow-up after discharge and had a favorable condition.

Conclusions: Transplant renal artery stenosis can cause regional hyperperfusion leading to adaptive FSGS, presenting with proteinuria and morphologically manifesting as a cellular variant of FSGS instead of the classic variant, which is usually closely related to hyperperfusion. The lesion must be differentiated from primary and other secondary FSGS. Removal of the hemodynamic abnormality can quickly relieve hypertension and proteinuria.

Background: Despite the known impact of steroid therapy on growth after kidney transplantation (KTx), steroids remain widely used in pediatric KTx recipients. Evidence on the effect on linear growth at minimal doses of steroids (6 mg/m² or 0.2 mg/kg/day) is limited. This study evaluated whether low doses of steroid therapy are associated with post-transplant growth failure.

Methods: Single-center retrospective cohort study. In total, 44 pediatric KTx recipients from 2005 to 2024 were collected. Differences in Z-Score and height before 6 months and after 6 and 12 months of KTx were assessed using Friedman rank tests. Linear mixed models were used to analyze the longitudinal effect of steroid therapy on growth outcomes.

Results: The mean age at KTx was 11 years (SD ± 3.8). Median prednisolone doses at 3 and 6 months after KTx were 0.23 (p25-75: 0.18-0.41) and 0.21 mg/k/day (0.14-0.28), respectively. The mean-height Z-score improved from -2.35 (SD ± 1.30) to 1.82 (SD ± 1.23) one year post-KTx. The percentage of patients with short stature (height Z-score ≤ -2SD) decreased from 65.1% at baseline (KTx) to 54.8% and 52.3% after 6 and 12 months, respectively. In multivariable analysis, time follow-up and age at KTx were associated with post-transplant growth. Steroid therapy shows a trend to reduce body height, but the interaction was not significant.

Conclusion: This single-center study found that pediatric KTx recipients receiving low-dose steroid therapy showed post-transplant improvements in height and Z-scores. Notably, the use of low-dose steroids did not significantly impair growth, although a slight downward trend in Z scores was noted.

Optimizing postoperative analgesia in pediatric liver transplantation remains challenging due to the balance between effective pain control, opioid-related adverse effects, and the risks of neuraxial techniques in coagulopathic patients. Regional anesthesia has gained attention as a potential opioid-sparing adjunct in this setting. This concise review aimed to systematically synthesize evidence on regional anesthesia techniques for pediatric liver transplant recipients. A concise review was conducted in a systematic method following PRISMA principles. Comprehensive searches were performed on February 21, 2025, using PubMed/MEDLINE and Scopus to identify studies evaluating regional anesthesia in pediatric liver transplantation. Inclusion criteria encompassed original studies involving pediatric liver transplant recipients receiving regional analgesia. Two reviewers independently screened titles, abstracts, and full texts, with discrepancies resolved by consensus. Six studies met inclusion criteria, encompassing 55 pediatric liver transplant patients (18 controls). Reported regional techniques included erector spinae plane (ESP) blocks (n = 24), thoracic epidural analgesia (TEA) (n = 4), and quadratus lumborum (QL) blocks (n = 9). Across studies, regional anesthesia was associated with decreased perioperative opioid use, early extubation in the operating room, and faster return of bowel function. ESP and QL blocks demonstrated favorable safety profiles, while TEA-performed only after confirming normal coagulation-was safely implemented without complications. Regional anesthesia may be beneficial as part of multimodal analgesia in carefully selected pediatric liver transplant recipients by reducing opioid exposure and supporting early recovery. However, evidence remains limited by small sample sizes and heterogeneous methodologies. Larger, prospective trials are needed to refine patient selection, establish standardized protocols, and confirm safety and efficacy.

Background: Utility of preoperative rotational thromboelastometry (ROTEM) over standard coagulation assays (SCAs) in predicting intraoperative bleeding during orthotopic liver transplantation (OLT) in children with liver failure (LF) remains unclear.

Methods: In this single-center retrospective cohort of pediatric OLT recipients, we compared the predictive values of preoperative ROTEM parameters (intrinsic pathway (INTEM) maximum clot firmness (MCF), extrinsic pathway (EXTEM) clotting time (CT), INTEM CT, and fibrinogen-based (FIBTEM) MCF) and the corresponding SCAs (platelet count, international normalized ratio (INR), activated partial thromboplastin time (aPTT), and fibrinogen level, respectively) for significant intraoperative bleeding (blood loss of > 22 mL/kg; i.e., ≥ 85th percentile for the cohort).

Results: Seventy-two children (44 with chronic liver disease, 15 with acute liver failure, and 13 with acute-on-chronic liver failure), with a median age of 39 (IQR 13-159) months, were included. Twelve children (17%) had significant intraoperative bleeding. Most ROTEM parameters and the corresponding SCAs strongly correlated, except for EXTEM CT and INR (Rho of 0.501 and confidence interval (CI) of 0.298-0.660). A combination of SCA parameters performed better than the combination of corresponding ROTEM parameters (area under the curve of 0.862 vs. 0.760; p = 0.029) in predicting significant intraoperative bleeding. Among coagulation parameters, only platelet count was associated with significant intraoperative bleeding (adjusted Odds Ratio of 1.02, CI of 1.00-1.04; p = 0.009).

Conclusions: ROTEM parameters and SCAs have comparable predictive value for significant intraoperative bleeding in children with LF requiring OLT. Further investigation is required to assess how ROTEM can be effectively used in managing coagulopathy in pediatric LF.

Background: Percutaneous transhepatic cholangiography (PTC) is commonly performed after liver transplantation in children for the management of bilioenteric anastomosis strictures. In this setting in which pressure in bile ducts is higher than in the venous system, accidental traumatic bilio-venous fistula may lead to bilhemia, that is, bile leakage into the bloodstream through the fistula, but this complication has never been reported in children after PTC.

Methods and results: We report the case of a young child who experienced severe bilhemia following PTC after liver transplantation. The blood levels of all four major bile components (i.e., cholesterol, bile acids, bilirubin, and phospholipids) were highly elevated, suggesting the presence of bilhemia. Conventional imaging techniques did not reveal the abnormal communication, which was confirmed through direct bile duct opacification. Placement of multiple stents within the hepatic vein, along with dilatation of a bilioenteric anastomosis stricture, enabled fistula occlusion and led to complete recovery.

Conclusion: This case demonstrates that bilhemia can occur in children after PTC and emphasizes the diagnosis and management modalities of this rare complication.