Pediatric Transplantation最新文献

Background: Solid organ transplantation requires complex and ongoing medical management that impacts the family system. However, the experiences of siblings of transplant recipients are not well described. Therefore, the purpose of this study was to elucidate the perspectives of siblings of pediatric kidney and liver transplant recipients.

Methods: Siblings (ages 12-17 years) of kidney and liver transplant recipients completed a semi-structured interview (Via Zoom) and demographic information. The interview data were analyzed using inductive content analysis.

Results: Twelve adolescents (9 males, 2 females, 1 non-binary; M = 15.25 Years, SD = 2.13) completed a virtual interview. Four major themes emerged describing the transplant experience: (1) Transplant changes the family system: Impact on family relationships, dynamics, and cohesiveness, (2) Transplant affects social-emotional development and adjustment, (3) new meaning assigned to family and increased commitment to the health of sibling, and (4) growth from the transplant experience as a way to help others.

Conclusions: These findings affirm that the transplant event is distressing and impacts the sibling, their relationships, and family functioning in the moment and for years afterward. Opportunities exist to raise healthcare providers' awareness of providing care through a family lens, which can positively impact the patient and the family. These findings are an initial step toward developing interventions that incorporate siblings of transplant recipients in healthcare interactions and create a more family-inclusive model of care in the transplant setting.

Background: Paxlovid, a fixed combination nirmatrelvir and ritonavir (NIM-RTV), is a potent inhibitor of cytochrome P450 3A4 (CYP3A4) isoenzyme. It is approved for the treatment of mild to moderate COVID-19 infections in patients at risk for serious infection. The metabolism of tacrolimus, a CYP3A4 substrate, is significantly reduced in those receiving NIM-RTV. Coadministration of NIM-RTV without tacrolimus dose reduction may result in toxicity. CYP3A4-inducing medications, including phenytoin, fosphenytoin or rifampin, may reverse toxicity while achieving rapid clearance.

Case presentation: A 14-year-old, 66.5 kg African American female with a history of chronic kidney disease stage 5 secondary to collapsing focal segmental glomerulosclerosis (FSGS) underwent an uncomplicated deceased donor kidney transplant at 12 years of age. Approximately 2.5 years after transplant, she tested positive for COVID-19. NIM-RTV was prescribed through a local pharmacy. She presented 3.5 days later with nausea, vomiting, fatigue, and oligo-anuria with acute kidney injury (AKI) and creatinine of 2.6 mg/dL from baseline of 0.7 mg/dL. Tacrolimus level was > 60 ng/mL. Phenytoin/fosphenytoin was initiated to induce tacrolimus clearance due to sustained AKI and neurological risk. Within 36 h, her tacrolimus level was 38 ng/mLwith improved urine output. After 3 days, her tacrolimus level 11.9 ng/mL and serum creatinine was near baseline.

Conclusions: To our knowledge, this is the first report of a pediatric kidney transplant patient with tacrolimus toxicity secondary to NIM-RTV therapy utilizing phenytoin/fosphenytoin to induce tacrolimus metabolism and prevent further toxicity. Heightened awareness of this interaction is paramount to reduce allograft injury and promote patient safety.

Background: Tacrolimus has a narrow therapeutic index with substantial inter- and intra-patient variability, requiring therapeutic drug monitoring (TDM). Influences beyond genetic and developmental factors need to be better understood. Recent studies among adult patients suggest that hemoglobin affects the apparent clearance (CL/F) of tacrolimus, whereas this and other potential factors in children are under-investigated.

Methods: After ethics approval, we performed a single-center retrospective cohort study of pediatric renal transplant recipients between January 1, 2004, and June 30, 2018. Patients without tacrolimus therapy or those with concomitant sirolimus were excluded. Apparent clearance (CL/F) was predicted for this analysis using a regression equation derived from 12-point pharmacokinetic (PK) profiles. The equation allowed for the estimation of the area under the curve (AUC) from trough levels, which were then used to calculate CL/F. Data were collected from electronic health records, and univariate and multivariate mixed-effect regression analyses were performed to evaluate the impact of hemoglobin, albumin, cholesterol, and HDL on CL/F.

Results: Thirty-three patients were included. The median age at transplantation was 10 years, 52% were female, and the median tacrolimus AUC was 133 ng•h/mL. CL/F correlated with hemoglobin (n = 1257, r = -0.3767, p < 0.0001), HDL-cholesterol (n = 236, r = -0.3973, p < 0.0001), and total cholesterol (n = 373, r = -0.1821, p = 0.0004). In multivariate mixed-effect regression, hemoglobin and cholesterol remained significant predictors of CL/F.

Conclusions: The present study suggests a moderate impact of hemoglobin and cholesterol on tacrolimus CL/F. Lower hemoglobin appears to increase CL/F, while higher cholesterol reduces it. These findings highlight the potential value of integrating biochemical parameters into dosing strategies to optimize TDM in pediatric kidney transplant recipients.

Background: Invasive fungal infections (IFI) remain a leading cause of mortality in liver transplant (LTX) patients with neutropenia. Hematopoietic growth factors and granulocyte transfusions (GTx) have been historically used in patients with neutropenia and after hematopoietic stem cell transplantation (HSCT) to treat IFI, but none thus far, in pediatric liver transplant recipients (PLTR).

Methods: We evaluated the safety and effect of GTx for life-threatening IFI, refractory to conventional antifungal treatment, in PLTR with hepatitis-associated aplastic anemia (HAAA) at King's College Hospital, London. We also conducted a literature review of GTX use in neutropenic pediatric patients with IFI.

Results: Two PLTR with HAAA, Case 1, 9-year-old male and Case 2, 6-year-old male received 6 weeks and 3 weeks of GTx. Both presented with acute liver failure requiring urgent LTX, complicated by bone marrow failure due to HAAA, multiple bacterial infections, and IFI. Case 1 developed invasive pulmonary aspergillosis (IPA), intra-abdominal (IAB) and bloodstream infection (BSI) with Candida guilliermondii and Candida fermentati whilst on four antifungals. Case 2 developed a necrotizing lesion on his arm, confirmed as mucormycosis, and had a BSI with Candida albicans and Candida glabrata whilst on two antifungals. Irradiated ABO group-compatible GTX was used as a bridge to control systemic dissemination of IFI. This provided some control in extremis until definitive treatment and improvement in neutrophil count by HSCT.

Conclusion: These are the first two cases to report the use of GTx in PLTR with bone marrow failure due to HAAA. Both patients tolerated GTx without side effects. We propose the consideration of GTx as adjunctive therapy for life-threatening IFI refractory to conventional antifungals in PLTR with severe neutropenia.

Background: Bilateral renal agenesis is a rare congenital urinary anomaly that leads to lethal pulmonary hypoplasia. Amnioinfusion has been used to improve survival outcomes with bilateral renal agenesis. However, there is limited information regarding the bladder anatomy of these patients.

Methods: Five children diagnosed in utero with bilateral renal agenesis who received serial amnioinfusion were included. The clinical course with respect to transplantation and bladder management is described.

Results: None of the children had viable bladders on radiographic or endoscopic evaluation. Four out of five children have received renal transplantation with concurrent cutaneous ureterostomy.

Conclusion: To our knowledge, this is the first report documenting bladder anatomy in living patients born with bilateral renal agenesis. Due to the bladder anomalies, there has been no standard of management of the urinary drainage at the time of transplant. We present the bladder management strategy for five patients with bilateral renal agenesis who received care at our facility.

Background: Pediatric liver transplantation in small children is a technical challenge; the use of liver grafts from living donors improves access but faces further technical difficulties due to size mismatch and anatomical variants. Avoiding outflow complications is a major concern in pediatric liver transplantations.

Case report: A 14-month-old girl weighing 6.2 kg with extrahepatic biliary atresia without ascites was referred to our hospital. Her father volunteered to donate, and the calculated volume of the left lateral section was 315 mL, with an estimated ratio of 4.5. Segment-3 vein drained into the middle hepatic vein. Given the high graft ratio, variant venous anatomy, and absence of ascites, a segment-2 monosegment graft was planned with a final ratio of 2.8, with no need for venous reconstruction and primary abdominal closure. No technical complications were observed after 6 years of follow-up.

Conclusion: This is the first case of monosegmental liver transplantation in Mexico. The use of this strategy, in the setting of aberrant hepatic vein anatomy, showed that the procedure can avoid unnecessary venous reconstruction and reduce the need for abdominal wall reconstruction or reintervention for closure.

Background: Congenital long QT syndrome (LQTS) is rare but significant, as it carries a risk for ventricular arrhythmias and sudden cardiac death. Its diagnosis can be made clinically by serial ECGs, ambulatory ECG monitoring, and exercise stress testing; however, genetic testing is confirmatory in the majority of cases.

Methods: Here, we describe a rare case of phenotype-positive LQTS in a 6-year-old heart transplant recipient, confirmed 5 years after transplantation to be genotype-positive and thus "acquired" from the transplanted heart.

Results: Recognition of a persistently prolonged QTc interval on the recipient's serial ECGs led to ambulatory ECG monitoring and exercise stress testing-both of which were suspicious for LQTS. Ultimately, genetic evaluation and cardiac biopsy were obtained and resulted positive for a KCNQ1 pathogenic variant associated with Type 1 LQTS.

Conclusion: Recognition of persistent, otherwise unexplained, ECG abnormalities can prompt genetic analysis of the allograft, leading to the potential life-saving diagnosis of a channelopathy.