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Jackson RL, Heyrend C, Bucher B, Brewer A, Peterson C, May LJ, Bonkowsky JL. Impact of Pharmacogenomic Testing in Pediatric Heart and Kidney Transplant. Pediatr Transplant 2025; 29:e70044. [PMID: 39924350 DOI: 10.1111/petr.70044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 01/20/2025] [Accepted: 01/25/2025] [Indexed: 02/11/2025]
Abstract
BACKGROUND Pediatric solid organ transplantation is a complex process including a tightly orchestrated medication regimen, essential for prevention of infection, rejection, graft failure, and mortality. Pharmacogenomic (PGx) testing tailors medication therapy to the individual patient, focusing on safety, efficacy, and avoidance of adverse effects. Implementation of PGx panel results into clinical practice for pediatric transplant patients has not been evaluated. METHODS Pediatric patients evaluated for heart, kidney, or combined heart-kidney transplant at a tertiary children's hospital from October 2021 to October 2023 received PGx panel testing. PRIMARY OUTCOME MEASURE Report the prevalence of actionable PGx variants for key genes impacting pharmacotherapy in pre- and post-heart and kidney transplant populations. RESULTS A total of 73 patients were included, predominately white (84.9%) and male (64.4%), with a mean age of 8.8 ± 6.4 years. Indications for PGx testing included evaluation for heart transplant (38.4%), kidney transplant (38.4%), combined heart-kidney transplant (4.1%), or to inform posttransplant care (19.2%). All patients had at least one actionable phenotype identified. 37 of 73 patients (50.7%) had at least one actionable phenotype for the transplant-specific genes captured including CYP3A5, SLCO1B1, G6PD, TPMT, prothrombin (Factor 2), and Factor V Leiden. 16 of 73 patients (21.9%) had actionable CYP3A5 phenotypes. 15 of 73 (20.5%) had actionable SLCO1B1 phenotypes. 9 of 73 patients (12.3%) had actionable TPMT phenotypes. 5 of 73 (6.8%) had Prothrombin or Factor V Leiden variants. CONCLUSIONS Routine pretransplant PGx testing provided information that was actionable and could be utilized to optimize posttransplant medications for all patients.
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Affiliation(s)
- Rachel L Jackson
- Department of Pharmacy, Primary Children's Hospital, Salt Lake City, Utah, USA
| | - Caroline Heyrend
- Department of Pharmacy, Primary Children's Hospital, Salt Lake City, Utah, USA
| | - Bridget Bucher
- Department of Pharmacy, Primary Children's Hospital, Salt Lake City, Utah, USA
| | - Ashlie Brewer
- Department of Pharmacy, Primary Children's Hospital, Salt Lake City, Utah, USA
| | - Caitlin Peterson
- Division of Nephrology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA
| | - Lindsay J May
- Division of Cardiology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA
| | - Joshua L Bonkowsky
- Division of Pediatric Neurology, Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA
- Center for Personalized Medicine, Primary Children's Hospital, Salt Lake City, Utah, USA
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Exeni AM, Falke GF, Montal S, Rigali MP, Cisnero DR, Berberian L, Marchionatti S, Heredia S, Allegrotti HE, Torres SF, Russo RD, Rozanec J. Pediatric KT in children up to 15 kg: A single-center experience. Pediatr Transplant 2021; 25:e14102. [PMID: 34309990 DOI: 10.1111/petr.14102] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 06/29/2021] [Accepted: 07/13/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND KT is the preferred treatment for ESRD in pediatrics. However, it may be challenging in those weighing ≤15 kg with potential complications that impact on morbidity and graft loss. METHODS This retrospective review reports our experience in KT in children, weighing ≤15 kg, and the strategies to reduce morbidity and mortality. RESULTS All patients were on RRT prior to KT. Patients reached ESRD mainly due to urologic malformations (54.54%). LD was performed in 82% of patients. The recipient's median age was 2.83 years, and median weight 12.280 kg. Male sex was predominant (73%). All patients required transfusions of PRBCs. There was a high requirement for ventilated support in patients post-KT with no relation to weight, amount of resuscitation used intra-operatively or ml/kg of PRBCs. One patient presented with stenosis of the native renal artery. No patients presented DGF, graft thrombosis, or surgical complications. No association was found between cold ischemia and eGFR at 1 year (p = .12). In univariate analysis, eGFR at 1 year is related to AR. eGFR at 3 years is related to the number of UTI. Median follow-up was 1363 days. Patient and graft survival were 100%. CONCLUSIONS KT in children ≤15 kg can be challenging and requires a meticulous perioperative management and surgical expertise. Patient and graft survival are excellent with low rate of complications.
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Affiliation(s)
| | | | - Silvina Montal
- Surgery, Hospital Universitario Austral, Pilar, Argentina
| | | | | | - Leandro Berberian
- Pediatric Surgery and Urology, Hospital Universitario Austral, Pilar, Argentina
| | - Sofia Marchionatti
- Pediatric Surgery and Urology, Hospital Universitario Austral, Pilar, Argentina
| | - Soledad Heredia
- Pediatric Surgery and Urology, Hospital Universitario Austral, Pilar, Argentina
| | | | | | | | - José Rozanec
- Urology, Hospital Universitario Austral, Pilar, Argentina
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Gunawardena T, Sharma H, Sharma AK, Mehra S. Surgical considerations in paediatric kidney transplantation: an update. RENAL REPLACEMENT THERAPY 2021. [DOI: 10.1186/s41100-021-00373-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Abstract
Background
Kidney transplantation has established itself as the most appropriate mode of renal replacement therapy for the majority with end-stage kidney disease. Although at present this is applicable for children as well as adults, a few decades back kidney transplantation was not considered a first-line option in children. This was due to inferior outcomes following transplantation in this age group compared to that of adults. These poor results were attributed to challenges in paediatric transplantation such as the shortage of suitable donors, technical difficulties in performing a sound vascular anastomosis and the adverse effects of immunosuppressive medication on growth and development. However, current patient and graft-centred outcomes after paediatric transplantation equal or surpass that of adults. The advances in evaluation and management of specific surgical concerns in children who undergo transplantation, such as pre-transplant native nephrectomy, correction of congenital anomalies of the urinary tract, placement of an adult-sized kidney in a small child and minimizing the risk of allograft thrombosis, have contributed immensely for these remarkable outcomes.
Conclusions
In this review, we aim to discuss surgical factors that can be considered unique for children undergoing kidney transplantation. We believe that an updated knowledge on these issues will be invaluable for transplant clinicians, who are dealing with paediatric kidney transplantation.
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Post-operative heparin reduces early venous thrombotic complications after orthotopic paediatric liver transplantation. BLOOD TRANSFUSION = TRASFUSIONE DEL SANGUE 2021; 19:495-505. [PMID: 33819140 DOI: 10.2450/2021.0388-20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Accepted: 02/18/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND Despite significant improvements in surgical techniques and medical care, thrombotic complications still represent the primary cause of early graft failure and re-transplantation following paediatric liver transplantation. There is still no standardized approach for thrombosis prevention. MATERIALS AND METHODS The study aimed to evaluate the effectiveness of early intravenous unfractionated heparin started 12 hours postoperatively at 10 UI/kg per hour and used a retrospective "before and after" design to compare the incidence of early thrombotic complications prior to (2002-2010) and after (2011-2016) the introduction of heparin in our institute. RESULTS From 2002 to 2016, 479 paediatric patients received liver transplantation in our institution with an overall survival rate over one year of 0.91 (95% CI: 0.87-0.94). Of 365 eligible patients, 244 did not receive heparin while 121 did receive heparin. We reported a lower incidence of venous thrombosis (VT) in the group treated with heparin: 2.5% (3/121) vs 7.9% (19/244) (p=0.038). All clinical and laboratory variables considered potential risk factors for VT were studied. By multivariate stepwise Cox proportional hazards models, heparin prophylaxis resulted significantly associated to a reduction in VT (HR=0.29 [95% CI: 0.08-0.97], p=0.045), while age <1 year was found to be an independent risk factor for VT (HR=2.62 [95% CI: 1.11-6.21]; p=0.028). DISCUSSION Early postoperative heparin could be considered a valid and safe strategy to prevent early VT after paediatric liver transplantation without a concomitant increase in bleeding. A future randomised control trial is mandatory in order to strengthen this conclusion.
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Survival Benefit of En Bloc Transplantation of Small Pediatric Kidneys in Children. Transplantation 2021; 104:2435-2443. [PMID: 32022736 DOI: 10.1097/tp.0000000000003158] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND En bloc transplantation of small pediatric kidneys in children may help expand the existing deceased donor pool; however, studies examining the long-term outcomes of en bloc transplantation in children are few. METHODS We used the Scientific Registry of Transplant Recipients to identify 149 pediatric en bloc recipients transplanted from October 1, 1987 to December 31, 2017. We used propensity scores to match 148 en bloc with 581 non-en bloc deceased donor recipients (matching variables: transplant age, gender, race, pretransplant dialysis, transplant center, and year). We evaluated patient and graft survival using Kaplan-Meier and Fleming-Harrington weighted log-rank test and examined survival benefit of en bloc transplantation versus remaining on the waiting list using the sequential Cox approach. We divided the study period into three 10-y intervals to assess the effect of era on outcomes. RESULTS Compared with non-en bloc recipients, en bloc recipients had lower 1-y graft survival (78.9% versus 88.9%; P = 0.007); however, when stratified by transplant era, lower 1-y survival was only observed in the oldest era (1987-1997). En bloc recipients had superior 10-y patient (89.0% versus 80.4%; P = 0.04) and graft survival (51.6% versus 39.9%; P = 0.04) compared with non-en bloc recipients. After multivariate adjustment, en bloc transplantation was associated with superior patient survival compared with remaining on the waiting list (adjusted hazard ratio: 0.58; 95% confidence interval: 0.36-0.95; P = 0.03). CONCLUSIONS En bloc transplantation of small pediatric kidneys in children is associated with superior long-term patient and graft survival. The increased risk of 1-y graft loss among en bloc recipients only appeared in the oldest era.
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Kim JK, Chua ME, Teoh CW, Lee MJ, Kesavan A, Hebert D, Lorenzo AJ, Farhat WA, Koyle MA. Assessment of prophylactic heparin infusion as a safe preventative measure for thrombotic complications in pediatric kidney transplant recipients weighing <20 kg. Pediatr Transplant 2019; 23:e13512. [PMID: 31169341 DOI: 10.1111/petr.13512] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Revised: 03/20/2019] [Accepted: 05/12/2019] [Indexed: 11/28/2022]
Abstract
Small-sized kidney recipients (<20 kg) are at high risk of allograft vessel thrombosis. HP has been used to mitigate this risk but may infer an increase in bleeding risks. Therefore, we aim to determine whether HP is a safe means to prevent thrombosis in small kidney transplant patients by comparing those who have received HP and those who have NHP. A retrospective review of patients < 20 kg who underwent kidney transplant in our institution from 2000 to 2015 was performed. At our institution, unfractionated heparin 10 units/kg/hour is used as HP since 2009. Patients at increased risk of thrombosis (previous thrombosis, thrombophilia, nephrotic syndrome) and bleeding (therapeutic doses of heparin, diagnosis of coagulopathy) were excluded. Fifty-six patients were identified (HP n = 46; NHP n = 10). Baseline demographics were similar between HP and NHP. There was no statistical difference in frequency of transfusions, surgical re-exploration, or thrombotic events between HP and NHP. The HP group was more likely to have drop in Hb > 20 g/L (67.4% vs 30.0%, P = 0.038), and those who had drop in Hb > 20 g/L were more likely to also require pRBC transfusions (63.0% vs 20.0%, P = 0.017). Within the HP group, those who had bleeding complications had similar Hb levels as those who did not at baseline and post-transplant. Outcomes in the HP and NHP groups were no different with respect to thrombosis or significant bleeding complications requiring pRBC transfusions or surgical intervention. Future prospective studies are required to investigate the balance of preventing thrombosis and risks of pRBC transfusions for small-sized kidney recipients.
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Affiliation(s)
- Jin K Kim
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Urology, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Michael E Chua
- Division of Urology, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Chia Wei Teoh
- Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.,Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Min Joon Lee
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.,Division of Urology, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Amre Kesavan
- Division of Urology, The Hospital for Sick Children, Toronto, Ontario, Canada.,School of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Diane Hebert
- Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.,Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada
| | - Armando J Lorenzo
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.,Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Walid A Farhat
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.,Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Martin A Koyle
- Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.,Department of Surgery, University of Toronto, Toronto, Ontario, Canada
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Nacoti M, Ruggeri GM, Colombo G, Bonanomi E, Lussana F. Thrombosis prophylaxis in pediatric liver transplantation: A systematic review. World J Hepatol 2018; 10:752-760. [PMID: 30386468 PMCID: PMC6206147 DOI: 10.4254/wjh.v10.i10.752] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 07/13/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To review current literature of thrombosis prophylaxis in pediatric liver transplantation (PLT) as thrombosis remains a critical complication.
METHODS Studies were identified by electronic search of MEDLINE, EMBASE and Cochrane Library (CENTRAL) databases until March 2018. The search was supplemented by manually reviewing the references of included studies and the references of the main published systematic reviews on thrombosis and PLT. We excluded from this review case report, small case series, commentaries, conference abstracts, papers which describing less than 10 pediatric liver transplants/year and articles published before 1990. Two reviewers performed study selection independently, with disagreements solved through discussion and by the opinion of a third reviewer when necessary.
RESULTS Nine retrospective studies were included in this review. The overall quality of studies was poor. A pooled analysis of results from studies was not possible due to the retrospective design and heterogeneity of included studies. We found an incidence of portal vein thrombosis (PVT) ranging from 2% to 10% in pediatric living donor liver transplantation (LDLT) and from 4% to 33% in pediatric deceased donor liver transplantation (DDLT). Hepatic artery thrombosis (HAT) was observed mostly in mixed LDLT and DDLT pediatric population with an incidence ranging from 0% to 29%. In most of the studies Doppler ultrasonography was used as a first line diagnostic screening for thrombosis. Four different surgical techniques for portal vein anastomosis were reported with similar efficacy in terms of PVT reduction. Reduced size liver transplant was associated with a low risk of both PVT (incidence 4%) and HAT (incidence 0%, P < 0.05). Similarly, aortic arterial anastomosis without graft interposition and microsurgical hepatic arterial reconstruction were associated with a significant reduced HAT incidence (6% and 0%, respectively). According to our inclusion and exclusion criteria, we did not find eligible studies that evaluated pharmacological prevention of thrombosis.
CONCLUSION Poor quality retrospective studies show the use of tailored surgical strategies might be useful to reduce HAT and PVT after PLT; prospective studies are urgently needed.
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Affiliation(s)
- Mirco Nacoti
- Department of Anesthesia and Intensive Care, Pediatric Intensive Care Unit, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
| | - Giulia Maria Ruggeri
- Department of Anesthesia and Intensive Care, Pediatric Intensive Care Unit, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
| | - Giovanna Colombo
- Department of Anesthesia and Intensive Care, Pediatric Intensive Care Unit, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
| | - Ezio Bonanomi
- Department of Anesthesia and Intensive Care, Pediatric Intensive Care Unit, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
| | - Federico Lussana
- Hematology and Bone Marrow Transplant Unit, Papa Giovanni XXIII Hospital, Bergamo 24127, Italy
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Markolović M, Ćupić M. The prevalence of herpesvirus infections in children and young adults transplant recipients - kidney and hematopoetic stem cells. MEDICINSKI PODMLADAK 2018. [DOI: 10.5937/mp69-16747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
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