Pediatric Transplantation最新文献

Background: Mucormycosis is a rare but devastating opportunistic fungal infection in immunocompromised hosts with particularly high morbidity and mortality in solid organ transplant recipients. Pediatric cases are exceedingly rare, and outcomes are often fatal.

Case presentation: We report a case of a 13-year-old girl on chronic peritoneal dialysis who received a deceased donor kidney transplant. She was at immunological risk due to a positive virtual crossmatch. Induction therapy included antithymocyte globulin and methylprednisolone, followed by a maintenance immunosuppressive regimen of prednisone, mycophenolate mofetil, and tacrolimus. Post-transplant, she developed early graft dysfunction, anuria, and hemodynamic instability. A graft biopsy showed acute tubular necrosis and C4d positivity prompting plasma exchange for suspected antibody-mediated rejection. Graft explant on day nine revealed angio-invasive mucormycosis due to Rhizopus arrhizus. The rapid onset suggested the infection may have been acquired from the donor. Despite antifungal therapy, she suffered from recurrent arterial pseudoaneurysms in the surgical bed. She died 91 days post-transplant from a ruptured iliac artery mycotic aneurysm.

Conclusion: This case highlights the challenges in diagnosing and managing mucormycosis in pediatric kidney transplant recipients. A high index of suspicion together with early recognition, aggressive surgical management, and appropriate antifungal treatment is essential. Donor derived fungal infections should be considered in cases of early onset disease. Unfortunately, outcomes remain poor.

Background: Clinical practice variation in the management of recurrent idiopathic focal segmental glomerulosclerosis (rFSGS) is poorly defined and likely hinders successful clinical trial design.

Methods: We conducted an online survey between June 2024 and September 2024 of Pediatric Nephrology Research Consortium (PNRC) and European Society for Pediatric Nephrology (ESPN) members to evaluate global clinical practice patterns in the management of pediatric rFSGS and physician perceptions of barriers to rFSGS clinical trial participation.

Results: Of 120 responses (50 PNRC members from the US and Canada and 70 ESPN members from Europe, Asia, and South America), all respondents were physicians and 50% were transplant program medical directors. Pretransplant mutation analysis was routine in 104 (87%) centers, and native nephrectomy was routine for patients with and without hypoalbuminemia in 77 (66%) and 23 (19%) centers, respectively. Forty-two (35%) centers reported routine therapeutic interventions to prevent rFSGS prior to kidney transplantation; this increased to 79 centers (66%) in patients with previous recurrence. Plasmapheresis was the first therapeutic intervention in most centers, although it was used significantly more often in North America (96%) than Europe (77%; p = 0.005). Rituximab was administered in 102 (85%) centers as treatment for rFSGS. Common barriers to recruitment and inclusion of patients in clinical trials of rFSGS were limited site resources (36%), recipient/family reluctance (10%), and operational and logistical issues (26%).

Conclusions: Heterogeneity of practice patterns in the management of pediatric rFSGS and barriers to clinical trials requires collaborative efforts to study and reach consensus on prevention and management of rFSGS.

Background: Diffuse infantile hepatic hemangiomas can lead to complications such as high-output heart failure, hypothyroidism, abdominal compartment syndrome, and hepatic failure. Medical management with propranolol is first-line therapy; however, treatment failure may occur in severe cases.

Methods: We described the case of a 2-month-old male with multiple cutaneous infantile hemangiomas and diffuse hepatic hemangiomas who presented with acute liver failure and cardiorespiratory insufficiency despite optimal treatment with propranolol. The patient was urgently listed for liver transplantation with a Pediatric End-Stage Liver Disease (PELD) score of 23 and weight < 5 kg. The infant underwent orthotopic liver transplantation from a deceased donor with caval replacement.

Results: Immunohistochemical staining of the liver and adrenal lesions was diffusely and strongly positive for GLUT1, consistent with infantile hemangioma. Liver function labs normalized immediately post-operatively without perioperative complications or rejection. The patient is growing and developing normally at 10 months after transplant.

Conclusions: This case highlights liver transplantation as a definitive treatment for hemangioma-related acute liver failure when propranolol therapy fails. Timely referral for transplantation is critical in optimizing outcomes in this rare but severe condition.

Partial Heart Transplantation (PHT) is a new type of transplant that enables implantation of living allogeneic semilunar valves capable of growing with pediatric patients. Semilunar valve function depends on the integrity of the leaflets, which are thin, avascular tissues composed of endothelial cells, interstitial cells, and extracellular matrix-features that closely parallel the architecture of the cornea. In this paper, we highlight this structural similarity and propose that corneal preservation and immune privilege, which were extensively studied over decades, may be frameworks that are adaptable to semilunar valves in PHT. This concept introduces a potentially impactful direction for improving the storage and viability of transplantable semilunar valves.

Background: Adolescent and young adult (AYA) kidney transplant recipients (KTR) are susceptible to risk-taking behaviors that peak during transfer from pediatric to adult healthcare, resulting in poorer outcomes. Professional guidelines support healthcare transition (HCT) practices to mitigate this risk; however, HCT perspectives and practices among providers, especially adult providers caring for KTR in the US, have not been widely studied.

Methods: An online survey of American Society of Transplantation (AST) members was conducted targeting both adult providers (AP) and pediatric providers (PP).

Results: The survey was completed by 135 respondents (predominantly US), including 61 PP and 74 AP. US respondents who disclosed their center ID represented 30% of all programs. Providers agreed that HCT was important (PP 97%, AP 94%) and a shared responsibility (PP 91% and AP 84%). Respondents to our survey frequently worked within transition programs (PP 70% vs. AP 48%), but the majority did not have a formal HCT policy to guide them (PP 43%, AP 21%). Multidisciplinary transition clinics were rare (PP 27%, AP 23%). Only 64% of PP included targeted HCT education either as part of a routine visit or a HCT session. Perceived barriers to providing HCT interventions were similar in both groups, including a lack of provider resources, outcomes tracking, provider communication, and patient/caregiver feedback.

Conclusion: Providers recognize the importance of HCT and the joint responsibility of PP and AP but have difficulty following best practices. A multipronged approach will be necessary to address barriers. Our survey reminds us of the gap that persists in providing AYAs with a seamless transfer from pediatric to adult care.

Background: Vascular complications persist as a challenging barrier to pediatric liver transplantation. With an incidence of 5%-10%, portal venous and hepatic arterial thromboses remain a major cause for early graft loss in this population. Real-time evaluation of flow parameters at various time points in the transplant course offers an ability to diagnose and even prevent such complications, and may consequently enhance long-term graft and recipient outcomes.

Methods: This review summarizes clinical studies describing liver hemodynamics in pediatric recipients and the utilization of flow parameters for the hepatic artery, portal vein, and hepatic vein.

Results: Preoperative parameters by doppler ultrasonography (DUS) predict the need for portal vein reconstruction which can assist with perioperative planning. Intraoperatively, real-time assessment of flow parameters predicts vascular complications and assists in evaluating the adequacy of graft inflow modulation (GIM). Postoperative surveillance remains critical to detection of both venous and arterial thrombosis and stenosis, but normal measurement ranges often vary based on patient age, underlying liver disease diagnosis, type of graft, and time from transplantation.

Conclusions: Future studies are needed to evaluate the most effective screening protocols and define intra-operative and post-operative measurements that should prompt surgeons to consider intervention in this vulnerable population.

Background: In pediatric kidney transplant recipients, native nephrectomy is sometimes performed to manage conditions such as polyuria, nephrotic syndrome, and recurrent infections. To minimize surgical morbidity, our center adopted a technique from the adult transplant program involving ligation of native ureters at the time of transplantation as an alternative to native nephrectomy in selected patients.

Methods: This retrospective study describes our center's experience with pediatric patients who underwent ureteral ligation at transplantation between December 2008 and December 2022. Patient selection was based on clinical judgment rather than predefined criteria.

Results: Sixteen patients underwent ureteral ligation, with polyuria (12/16) and proteinuria associated with focal segmental glomerulosclerosis (4/16) as the primary indications. Ligation was unilateral in 5 patients and bilateral in 11. The average follow-up was 5.7 years. No operative complications directly attributable to ureteral ligation were observed, including native kidney pyelonephritis or need for reoperation. Although post-transplant imaging often revealed hydronephrosis of the native kidneys, it had no clinical consequences. Late postoperative hypertension occurred in 31% of the ligation group compared to 47% of controls without ligation, while new-onset hypertension was more common in the ligation group (18.8% vs. 5.1%). Pain scores postoperatively were comparable between groups.

Conclusions: This technical report suggests that native ureteral ligation at pediatric kidney transplantation is feasible in selected patients but represents an empirical, non-standard-of-care approach. Prospective comparative studies are needed to refine patient selection and assess long-term outcomes.

Background: Urothelial bladder carcinoma is extremely rare in children and its association with BK virus infection remains unclear.

Methods: We describe the case of an 11-year-old girl who developed a urothelial carcinoma of the bladder four years after receiving her first kidney transplant. Kidney failure was secondary to nephronophthisis (NPHP6 variant), diagnosed in the neonatal period and associated with Leber congenital amaurosis and intellectual disability. She underwent peritoneal dialysis for four years before kidney transplantation at 6.5 years of age. Five months post-transplant, she developed BK virus-associated nephropathy, leading to chronic allograft dysfunction. Four years later, a routine ultrasound revealed an asymptomatic bladder mass without evidence of extension. The lesion was resected endoscopically and later managed with partial cystectomy.

Results: Histopathologic analysis confirmed a high-grade invasive urothelial carcinoma (pT2). Immunohistochemistry showed SV40 positivity, consistent with BK virus-induced neoplasia, while non-tumoral cells were negative. BK viremia had been undetectable one year prior to diagnosis. The patient remained disease-free for seven years following surgery, without adjuvant therapy.

Conclusion: The involvement of BK virus in the development of bladder cancer has not yet been clarified. This case supports a possible role of BK virus in urothelial tumorigenesis, particularly in immunosuppressed transplant recipients.

Background: This study examined the associations between mental health diagnoses, medication nonadherence, and healthcare utilization among pediatric solid organ transplant (SOT) recipients using a large, multistate electronic health record dataset.

Methods: Data were drawn from 2037 pediatric SOT recipients (ages 0-25 years) within the OneFlorida+ Data Trust (2012-2018). Mental health conditions (depression, anxiety, post-traumatic stress disorder [PTSD], and attention-deficit/hyperactivity disorder [ADHD]), clinician-documented nonadherence, and healthcare utilization outcomes, emergency department (ED) and inpatient (IP) visits, were identified using ICD-9/10-CM codes. Logistic regression estimated predictors of nonadherence, while negative binomial regression models with log-offsets for follow-up time produced incidence rate ratios (IRRs) for utilization outcomes. Models adjusted for demographic and clinical covariates including age, sex, race, ethnicity, and organ type.

Results: Mental health diagnoses were common: anxiety (21.6%), depression (15.3%), ADHD (13.7%), and PTSD (13.1%). Clinician-documented nonadherence occurred in 13.3% of patients and was associated with older age, non-White race, depression (OR = 2.85, 95% CI 1.75-4.62), and anxiety (OR = 2.29, 95% CI 1.62-3.23). Nonadherence independently predicted increased healthcare utilization, with approximately twice the rate of ED (IRR = 2.02, 95% CI 1.68-2.43) and IP (IRR = 2.00, 95% CI 1.67-2.40) visits. Anxiety and PTSD also remained significant predictors of elevated utilization across models.

Conclusions: Mental health conditions and medication nonadherence are common and independently associated with higher acute care utilization among pediatric SOT recipients. Integrating standardized psychosocial assessment and adherence interventions into routine post-transplant care may help mitigate preventable hospitalizations and improve long-term outcomes.