Personalized Medicine in Organ Transplantation

A special issue of Journal of Personalized Medicine (ISSN 2075-4426). This special issue belongs to the section "Clinical Medicine, Cell, and Organism Physiology".

Deadline for manuscript submissions: closed (5 October 2023) | Viewed by 11625

Special Issue Editors

Department of Surgery, Division of Multiorgan Transplant and Hepatobiliary Surgery, University of Texas Medical Branch, Galveston, TX, USA
Interests: kidney transplantation; transplant surgery; organ transplantation; organ donation; transplant immunology; chronic liver failure; liver transplantation; graft survival; liver cell carcinoma
Chief of Transplant, Medical Director of Kidney Transplantation, Division of Nephrology, University of Texas Medical Branch, Galveston, TX, USA
Interests: kidney transplantation; transplant surgery; organ transplantation; organ donation; transplant immunology; transplant medicine
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Special Issue Information

Dear Colleagues,

Since the first successful human-to-human kidney transplant between identical twins in 1954, personalized medicine has permeated the field of transplantation due to the intricacies of donor-recipient matching. Indeed, transplantation has been nearly synonymous with personalized medicine, requiring specialized approaches to ABO blood typing, HLA classification, infectious disease treatment and prophylaxis, medication dosing, and surgical techniques.  In the current era of precision medicine initiatives, the field of transplantation is ripe for innovation that is accelerating at a pace akin to Moore’s Law. Practitioners in the field are constantly striving to provide the best possible care for patients in the context of shifting multi-level regulations and an urgency to meet the increasing demands for transplantable organs. Despite the progress, solutions to ongoing problems remain elusive, such as equitable allocation policies, pre-transplant risk assessment, optimal induction and maintenance immunosuppression regimens, and intelligent allograft monitoring protocols. All these and more are needed to ensure improved allograft and patient survival while minimizing the risk of infectious and other complications.

This Special Issue of the Journal of Personalized Medicine aims to highlight some of the latest studies applying precision medicine to improve the care of people with end stage organ disease who are in need of or have undergone transplantation.

Dr. Michael L. Kueht
Dr. Muhammad Mujtaba
Guest Editors

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Keywords

  • organ transplantation
  • personalized medicine
  • precision medicine

Published Papers (8 papers)

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Research

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14 pages, 1786 KiB  
Article
Pancreas Rejection in the Artificial Intelligence Era: New Tool for Signal Patients at Risk
by Emanuel Vigia, Luís Ramalhete, Rita Ribeiro, Inês Barros, Beatriz Chumbinho, Edite Filipe, Ana Pena, Luís Bicho, Ana Nobre, Sofia Carrelha, Mafalda Sobral, Jorge Lamelas, João Santos Coelho, Aníbal Ferreira and Hugo Pinto Marques
J. Pers. Med. 2023, 13(7), 1071; https://doi.org/10.3390/jpm13071071 - 29 Jun 2023
Cited by 3 | Viewed by 1057
Abstract
Introduction: Pancreas transplantation is currently the only treatment that can re-establish normal endocrine pancreatic function. Despite all efforts, pancreas allograft survival and rejection remain major clinical problems. The purpose of this study was to identify features that could signal patients at risk of [...] Read more.
Introduction: Pancreas transplantation is currently the only treatment that can re-establish normal endocrine pancreatic function. Despite all efforts, pancreas allograft survival and rejection remain major clinical problems. The purpose of this study was to identify features that could signal patients at risk of pancreas allograft rejection. Methods: We collected 74 features from 79 patients who underwent simultaneous pancreas–kidney transplantation (SPK) and used two widely-applicable classification methods, the Naive Bayesian Classifier and Support Vector Machine, to build predictive models. We used the area under the receiver operating characteristic curve and classification accuracy to evaluate the predictive performance via leave-one-out cross-validation. Results: Rejection events were identified in 13 SPK patients (17.8%). In feature selection approach, it was possible to identify 10 features, namely: previous treatment for diabetes mellitus with long-term Insulin (U/I/day), type of dialysis (peritoneal dialysis, hemodialysis, or pre-emptive), de novo DSA, vPRA_Pre-Transplant (%), donor blood glucose, pancreas donor risk index (pDRI), recipient height, dialysis time (days), warm ischemia (minutes), recipient of intensive care (days). The results showed that the Naive Bayes and Support Vector Machine classifiers prediction performed very well, with an AUROC and classification accuracy of 0.97 and 0.87, respectively, in the first model and 0.96 and 0.94 in the second model. Conclusion: Our results indicated that it is feasible to develop successful classifiers for the prediction of graft rejection. The Naive Bayesian generated nomogram can be used for rejection probability prediction, thus supporting clinical decision making. Full article
(This article belongs to the Special Issue Personalized Medicine in Organ Transplantation)
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9 pages, 1345 KiB  
Article
Donor, Recipient and Surgeon Sex and Sex-Concordance and their Impact on Liver Transplant Outcome
by Laura Ioana Mazilescu, Isabel Bernheim, Jürgen Treckmann and Sonia Radunz
J. Pers. Med. 2023, 13(2), 281; https://doi.org/10.3390/jpm13020281 - 01 Feb 2023
Cited by 1 | Viewed by 981
Abstract
(1) Background: Patient sex is associated with differential outcome of many procedures although the exact mechanisms remain unknown. Especially in transplant surgery, surgeon-patient sex-concordance is rarely present for female patients and outcome may be negatively affected. (2) Methods: In this single-center retrospective cohort [...] Read more.
(1) Background: Patient sex is associated with differential outcome of many procedures although the exact mechanisms remain unknown. Especially in transplant surgery, surgeon-patient sex-concordance is rarely present for female patients and outcome may be negatively affected. (2) Methods: In this single-center retrospective cohort study, recipient, donor, and surgeon sex were evaluated and short- and long-term outcome was analyzed with regards to sex and sex-concordance of patients, donors, and surgeons. (3) Results: We included 425 recipients in our study; 50.1% of organ donors, 32.7% of recipients, and 13.9% of surgeons were female. Recipient-donor sex concordance was present in 82.7% of female recipients and in 65.7% of male recipients (p = 0.0002). Recipient-surgeon sex concordance was present in 11.5% of female recipients and in 85.0% of male recipients (p < 0.0001). Five-year patient survival was comparable between female and male recipients (70.0% vs. 73.3%, p = 0.3978). Five-year patient survival of female recipients treated by female surgeons was improved without reaching significance (81.3% vs. 68.4%, p = 0.3621). (4) Conclusions: Female recipients and female surgeons are underrepresented in liver transplant surgery. Societal factors influencing outcome of female patients suffering from end-stage organ failure need to be further examined and acted upon to possibly improve the outcome of female liver transplant recipients. Full article
(This article belongs to the Special Issue Personalized Medicine in Organ Transplantation)
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10 pages, 1092 KiB  
Article
Bioelectrical Impedance Analysis for Preoperative Volemia Assessment in Living Donor Hepatectomy
by Suk-Won Suh
J. Pers. Med. 2022, 12(11), 1755; https://doi.org/10.3390/jpm12111755 - 22 Oct 2022
Cited by 1 | Viewed by 1316
Abstract
Donor safety remains an important concern. We introduced preoperative bioelectrical impedance analysis (BIA) in living donor hepatectomy, as it is a practical method for volemia assessment with the advantages of noninvasiveness, rapid processing, easy handling, and it is relatively inexpensive. We analyzed 51 [...] Read more.
Donor safety remains an important concern. We introduced preoperative bioelectrical impedance analysis (BIA) in living donor hepatectomy, as it is a practical method for volemia assessment with the advantages of noninvasiveness, rapid processing, easy handling, and it is relatively inexpensive. We analyzed 51 living donors who underwent right hemihepatectomy between July 2015 and May 2022. The ratio of extracellular water:total body water (ECW/TBW; an index of volemic status) was measured. ECT/TBW < 0.378 was correlated to central venous pressure (CVP) < 5 mm Hg in a previous study and we used this value for personalized preoperative management. In the BIA group (n = 21), donors with ECW/TBW ≥ 0.378 (n = 12) required whole-day nothing by mouth (NPO), whereas those with ECW/TBW < 0.378 (n = 9) required midnight NPO, similar to the control group (n = 30). In comparison with the control group, the BIA group had a significantly lower central venous pressure (p < 0.001) from the start of surgery to the end of surgery, leading to a better surgical field grade (p = 0.045) and decreased operative duration (240.5 ± 45.6 vs. 276.5 ± 54.0 min, p = 0.016). A cleaner surgical field (surgical field grade 1) was significantly associated with decreased operative duration (p = 0.001) and estimated blood loss (p < 0.001). Preoperative BIA was the only significant predictor of a cleaner surgical field (odds ratio, 6.914; 95% confidence interval, 1.6985–28.191, p = 0.007). In conclusion, preoperative volemia assessment using BIA can improve operative outcomes by creating a favorable surgical environment in living donor hepatectomy. Full article
(This article belongs to the Special Issue Personalized Medicine in Organ Transplantation)
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8 pages, 241 KiB  
Article
Splenic Artery Ligation: An Ontable Bail-Out Strategy for Small-for-Size Remnants after Major Hepatectomy: A Retrospective Study
by Kassiani Theodoraki, Antonios Vezakis, Dimitrios Massaras, Aspasia Louta, Nikolaos Arkadopoulos and Vassilios Smyrniotis
J. Pers. Med. 2022, 12(10), 1687; https://doi.org/10.3390/jpm12101687 - 10 Oct 2022
Viewed by 1130
Abstract
It has been reported that the prevention of acute portal overpressure in small-for-size liver grafts leads to better postoperative outcomes. Accordingly, we aimed to investigate the feasibility of the technique of splenic artery ligation in a case series of thirteen patients subjected to [...] Read more.
It has been reported that the prevention of acute portal overpressure in small-for-size liver grafts leads to better postoperative outcomes. Accordingly, we aimed to investigate the feasibility of the technique of splenic artery ligation in a case series of thirteen patients subjected to major liver resections with evidence of small-for-size syndrome and whether the maneuver results in the reduction of portal venous pressure and flow. The technique was successful in ten patients, with splenic artery ligation alleviating portal hypertension significantly. Three patients required the performance of a portocaval shunt for the attenuation of portal hypertension. Portal inflow modulation via splenic artery ligation is a technically simple technique that can prove useful in the context of major hepatectomies as well as in liver transplantations and the early evaluation and modification of portal venous pressure post hepatectomy can be used as a practical tool to guide the effect of the intervention. Full article
(This article belongs to the Special Issue Personalized Medicine in Organ Transplantation)
12 pages, 1225 KiB  
Article
Do Patients with Autoimmune Conditions Have Less Access to Liver Transplantation despite Superior Outcomes?
by Stephanie S. Keeling, Malcolm F. McDonald, Adrish Anand, Cameron R. Goff, Caroline R. Christmann, Spencer C. Barrett, Michael Kueht, John A. Goss, George Cholankeril and Abbas Rana
J. Pers. Med. 2022, 12(7), 1159; https://doi.org/10.3390/jpm12071159 - 17 Jul 2022
Viewed by 1493
Abstract
Orthotopic liver transplantation (OLT) is a lifesaving therapy for patients with irreversible liver damage caused by autoimmune liver diseases (AutoD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, it is unclear how access to transplantation differs among [...] Read more.
Orthotopic liver transplantation (OLT) is a lifesaving therapy for patients with irreversible liver damage caused by autoimmune liver diseases (AutoD) including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). Currently, it is unclear how access to transplantation differs among patients with various etiologies of liver disease. Our aim is to evaluate the likelihood of transplant and the long-term patient and graft survival after OLT for each etiology for transplantation from 2000 to 2021. We conducted a large retrospective study of United Network for Organ Sharing (UNOS) liver transplant patients in five 4-year eras with five cohorts: AutoD (PBC, PSC, AIH cirrhosis), alcohol-related liver disease (ALD), hepatocellular carcinoma (HCC), viral hepatitis, and nonalcoholic steatohepatitis (NASH). We conducted a multivariate analysis for probability of transplant. Intent-to-treat (ITT) analysis was performed to assess the 10-year survival differences for each listing diagnosis while accounting for both waitlist and post-transplant survival. Across all eras, autoimmune conditions had a lower adjusted probability of transplant of 0.92 (0.92, 0.93) compared to ALD 0.97 (0.97, 0.97), HCC 1.08 (1.07, 1.08), viral hepatitis 0.99 (0.99, 0.99), and NASH 0.99 (0.99, 1.00). Patients with AutoD had significantly better post-transplant patient and graft survival than ALD, HCC, viral hepatitis, and NASH in each and across all eras (p-values all < 0.001). Patients with AutoD had superior ITT survival (p-value < 0.001, log rank test). In addition, the waitlist survival for patients with AutoD compared to other listing diagnoses was improved with the exception of ALD, which showed no significant difference (p-value = 0.1056, log rank test). Despite a superior 10-year graft and patient survival in patients transplanted for AutoD, patients with AutoD have a significantly lower probability of receiving a liver transplant compared to those transplanted for HCC, ALD, viral hepatitis, and NASH. Patients with AutoD may benefit from improved liver allocation while maintaining superior waitlist and post-transplant survival. Decreased access in spite of appropriate outcomes for patients poses a significant risk for increased morbidity for patients with AutoD. Full article
(This article belongs to the Special Issue Personalized Medicine in Organ Transplantation)
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Review

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30 pages, 1377 KiB  
Review
Contemporary Biomarkers for Renal Transplantation: A Narrative Overview
by Dorin Novacescu, Silviu Constantin Latcu, Razvan Bardan, Liviu Daminescu and Alin Adrian Cumpanas
J. Pers. Med. 2023, 13(8), 1216; https://doi.org/10.3390/jpm13081216 - 31 Jul 2023
Cited by 1 | Viewed by 1548
Abstract
Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to [...] Read more.
Renal transplantation (RT) is the preferred treatment for end-stage renal disease. However, clinical challenges persist, i.e., early detection of graft dysfunction, timely identification of rejection episodes, personalization of immunosuppressive therapy, and prediction of long-term graft survival. Biomarkers have emerged as valuable tools to address these challenges and revolutionize RT patient care. Our review synthesizes the existing scientific literature to highlight promising biomarkers, their biological characteristics, and their potential roles in enhancing clinical decision-making and patient outcomes. Emerging non-invasive biomarkers seemingly provide valuable insights into the immunopathology of nephron injury and allograft rejection. Moreover, we analyzed biomarkers with intra-nephron specificities, i.e., glomerular vs. tubular (proximal vs. distal), which can localize an injury in different nephron areas. Additionally, this paper provides a comprehensive analysis of the potential clinical applications of biomarkers in the prediction, detection, differential diagnosis and assessment of post-RT non-surgical allograft complications. Lastly, we focus on the pursuit of immune tolerance biomarkers, which aims to reclassify transplant recipients based on immune risk thresholds, guide personalized immunosuppression strategies, and ultimately identify patients for whom immunosuppression may safely be reduced. Further research, validation, standardization, and prospective studies are necessary to fully harness the clinical utility of RT biomarkers and guide the development of targeted therapies. Full article
(This article belongs to the Special Issue Personalized Medicine in Organ Transplantation)
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9 pages, 549 KiB  
Review
The Current State of Donor-Derived Cell-Free DNA Use in Allograft Monitoring in Kidney Transplantation
by Michael L. Kueht, Laxmi Priya Dongur, Matthew Cusick, Heather L. Stevenson and Muhammad Mujtaba
J. Pers. Med. 2022, 12(10), 1700; https://doi.org/10.3390/jpm12101700 - 12 Oct 2022
Cited by 3 | Viewed by 1622
Abstract
Renal transplantation is the definitive therapy for patients suffering from end-stage renal disease. Though there have been significant advances in immunosuppression in these patients, there is still up to 30% acute and subclinical rejection. Current standards employ lab markers of renal function and [...] Read more.
Renal transplantation is the definitive therapy for patients suffering from end-stage renal disease. Though there have been significant advances in immunosuppression in these patients, there is still up to 30% acute and subclinical rejection. Current standards employ lab markers of renal function and biopsy results for accurate diagnosis. However, donor derived cell-free DNA has been identified as a measurable lab test that may be able to adequately diagnose rejection at early stages, precluding the need for invasive procedures like biopsy. We obtained published data directly from companies that offer ddcfDNA assay tests and additionally conducted a literature review using databases like PUBMED and NIH U.S. National Library of Medicine. We comprehensively compare the most used ddcfDNA assays, delineate their respective limitations, and further explore future directions in the utility of ddcfDNA in renal transplant patients. Full article
(This article belongs to the Special Issue Personalized Medicine in Organ Transplantation)
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14 pages, 916 KiB  
Review
Current Approaches in the Allocation of Liver Transplantation
by Vlad Alexandru Ionescu, Camelia Cristina Diaconu, Simona Bungau, Viorel Jinga and Gina Gheorghe
J. Pers. Med. 2022, 12(10), 1661; https://doi.org/10.3390/jpm12101661 - 06 Oct 2022
Cited by 2 | Viewed by 1490
Abstract
In recent decades, important advances have been made in the field of liver transplantation. One of the major problems remaining in this area is the small number of donors. Thus, recent data bring multiple updates of the indications and contraindications of this therapeutic [...] Read more.
In recent decades, important advances have been made in the field of liver transplantation. One of the major problems remaining in this area is the small number of donors. Thus, recent data bring multiple updates of the indications and contraindications of this therapeutic method. The main goal is to increase the number of patients who can benefit from liver transplantation, a therapeutic method that can improve life expectancy and the quality of life of patients with end-stage liver disease. Another goal in the management of these patients is represented by the optimal care of those on the waiting list during that period. A multidisciplinary team approach is necessary to obtain the best results for both the donor and the recipient. Full article
(This article belongs to the Special Issue Personalized Medicine in Organ Transplantation)
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