Transplantation Reports最新文献

Introduction

The new LCP-formulation of tacrolimus (Tac) has shown pharmacokinetic advantages in patients after liver transplantation that are associated with better adherence. The influence of prolonged release Tac on adherence, trough levels and dosing of Tac remains unclear.

Methods

A prospective study was performed in 62 patients from two centers, who were switched to LCP-Tac after kidney transplantation, to assess adherence as defined by the Tac trough level coefficient of variation (CoV) (primary endpoint) and BAASIS© Score, as well as kidney function, Tac trough level and tacrolimus dose.

Results

BAASIS© Score and Tac trough level CoV demonstrated good adherence over the study period, with no difference between the study timepoints (0.26 ± 0.16 at study start and 0.26 ± 0.11 at study end, p = 0.976, paired t-test). Graft function and Tac trough levels remained stable, and Tac dose could be reduced.

Conclusions

A switch to LCP-Tac is feasible and leads to stable adherence, graft function and Tac trough levels, in combination with lower Tac doses.

The virtual crossmatch is used in transplant medicine to assess the compatibility of organ donors and recipients. Virtual crossmatch methods vary considerably across institutions; require highly trained HLA laboratory experts and clinicians for interpretation; and do not generate data in a standardized format suitable for comparison across institutions. It is not known if standardized multi-center data collection and reporting could potentially facilitate the development of data-driven immunologic decision-making. We sought to examine the feasibility of an algorithmic approach to interpreting virtual crossmatch data.

We examined Histocompatibility and Immunogenetics laboratory data from 1,152 transplant patients and 1,180 donors from an academic medical transplant center over a ten-year time interval. Principal component analysis was used to simplify the complex high-dimensional data with rare outcomes into a format better suited for analysis. Machine learning models were used to predict negative flow crossmatch results. A training subset of the oldest 80% of the data was used to identify the top-performing model. The model's performance was assessed on the newest 20% of the data with the area under receiver operating characteristic curve (AUC).

The final dataset included 2205 crossmatch results from 1446 patient-donor pairs of which 2019 (91.6%) were negative and 186 (8.4%) positive. The top-performing model test set AUC was 0.80.

This study offers the first proof-of-concept of the feasibility of an algorithmic approach to estimate physical crossmatch results. Standardized, multi-institution data collection is necessary to further explore the possibility of a standardized, data-driven virtual crossmatch process.

Background

Renal transplant adds survival benefits to end-stage renal disease patients over dialysis, and a similar concept applies to elderly patients. Some of the challenges of transplanting old patients may involve age-related cancers and comorbid conditions such as cardiovascular disease. Studies had shown that advanced age is associated with better outcomes compared to dialysis despite receiving poorer quality organs.

Aim

This extended literature review aims to identify the common complications, outcomes, and survival benefits of kidney transplantation in the elderly population.

Methods

An extended literature review was done to identify studies that compared elderly transplant recipients with the younger kidney transplant recipient population. The study population included elderly kidney recipients aged sixty and above and younger kidney recipients below the age of sixty. This literature review aims to discuss complications facing elderly kidney recipients and compare transplant outcomes to younger kidney recipients. PubMed, Midline, and google scholar databases were searched and papers meeting the pre-set inclusion criteria were identified.

Results

A total of 212 papers were identified. After screening the results, 12 papers met the inclusion criteria and were included for review. 10/12 papers included patients' age cutoff point, one paper had cut-off age between 60 and 80 years, while the last paper recruited patients with ages above 70. Most of the studies mentioned young group age as below 60, 2/12 papers divided the young group into further subgroups of age. Two studies used paired donor organs for both young and elderly groups to eliminate donor bias. While other studies used living, deceased, or both living and deceased donors for both elderly and young groups. One study matched donor type and gender in both groups. The studies looked at patient and graft survival and complications. Elderly transplant patients suffered more hospitalization, infections, cardiovascular complications, malignancy, and surgical complications. Post-transplant diabetes was higher in the young recipient group in one study.

Conclusion

In the case of elderly renal transplant recipients, the cut-off point for age to perform renal transplant is not clear but studies showed better survival and cost-effectiveness in elderly patients compared to patients on the waiting list even in older patient cohorts

Vascular endothelial growth factors are proteins that participate in processes related to normal physiology, solid tumors and hematologic malignancies; however, their role in hematopoietic stem cell transplantation (HSCT) requires further investigation. To better define the role and changes in vascular endothelial growth factor-A (VEGF-A) in the context of HSCT, we conducted an observational prospective analysis of VEGF-A expression during the early period after HSCT in pediatric patients. Thirty-seven pediatric patients who underwent hematopoietic stem cell transplantation at the Federico Gómez Children's Hospital in Mexico between June 2016 and July 2018 were prospectively enrolled in this study. Ribonucleic acid was isolated from the venous blood of these patents on Days 0, +7, +14, +21, +28, and +35 after transplantation, and TaqMan reverse transcription-polymerase chain reaction was performed using specific primers and a probe for VEGF-A. The concentration of VEGF-A was determined using a complementary deoxyribonucleic acid control. Data were analyzed using one-way ANOVA and Dunnett post hoc tests. Statistical analysis was performed using SPSS version 25. There were significant differences in the concentrations of VEGF-A between Day 0 vs. Day +28 (p = 0.009 95% CI=0.02–0.24), Day 0 vs. Day +35 (p = 0.006; 95% CI=0.03–0.28) and Day 7 vs. Day + 35 (p = 0.006; 95% CI=0.03–0.24) after allogeneic HSCT. We observed significant increases in the VEGF-A concentration during the early period after stem cell transplantation in pediatric patients. Our results provide important insights that should be considered a basis for future clinical trials of pediatric HSCT, including the monitoring of VEGF-A concentrations, proteins and in vitro analysis.

Although the incidence of acute antibody mediated rejection in liver transplantation is low, the consequences of acute antibody mediated rejection can be devastating, often leading to severe fibrotic changes and early graft loss. Conventional treatment modalities for management of moderate-to-severe acute antibody mediated rejection in liver transplant continue to rely on of corticosteroids, plasmapheresis, and intravenous immunoglobulin. However, management of refractory, severe antibody mediated rejection remains without a clear gold-standard approach. This case report describes successful first use of Imlifidase, an Ig-G degrading enzyme, for management of acute refractory antibody mediated rejection following orthotopic liver transplant. This 41-year-old woman developed acute antibody meditated rejection and donor specific antibodies within two weeks of undergoing an A2 to O liver transplant. Following unsuccessful treatment with conventional modalities, treatment with Imlifidase resulted in normalization of liver function, resolution of antibody mediated rejection on surveillance biopsy, and disappearance of donor specific antibodies. Imlifidase could represent a promising treatment for refractory antibody mediated rejection in liver transplantation and warrants further study.

Over the past half a century, kidney transplants have increased significantly and more patients that are elderly are receiving kidney transplants. As a result, the eligibility of patients with prostate cancer who wish to receive a kidney transplant has become a significant issue facing the transplant community. Many questions have arisen because prostate cancer is an extremely variable disease that many times do not harm the patients but at other times, can cause the death of the patient.

If a patient has prostate cancer, should he be allowed to receive a kidney transplant? Should he receive the transplant after treatment for prostate cancer or without such treatment? How should the transplant community determine his eligibility? Most agree that those with high-risk prostate cancer should be treated first and have a waiting period prior to kidney transplant. Almost all low-risk prostate cancer patients are candidates for active surveillance. More and more urologists are doing active surveillance for favorable intermediate risk prostate cancer patients. We believe that all patients who are reasonable candidates for active surveillance based on the National Comprehensive Cancer Network (NCCN) guidelines for prostate cancer are reasonable candidates for kidney transplant without treatment for prostate cancer. We recommend using a combination of shared-decision making that involves prostate cancer risk-stratification as well as adjunctive tests such as imaging with multiparametric MRI (mpMRI) and genomic testing such as Decipher, Oncotype DX or Polaris, in order to inform whether or not patients with prostate cancer can receive a kidney transplant without treatment for prostate cancer.

Aim

Our objective was to report the outcomes of ABO-incompatible (ABOi) transplants and seek solutions to pretransplant desensitization, peri and postoperative bleeding events, acute rejection and infection-related mortality.

Methods

We retrospectively analyzed 247 consecutive ABOi kidney transplantations at our center from June 2012 to March 2020. The primary outcomes were patient, graft, and death-censored graft survival over 5 years.

Results

A total of 31 patients received thymoglobulin and 216 patients received basiliximab induction. Patient survival rates with basiliximab induction at 1, 3, and 5 years were 97.8%, 93.5%, and 93.5%, respectively; corresponding graft survival rates were 95.1%, 86.6%, and 85.2%, respectively. Overall, biopsy-proven acute rejection occurred in 11.7% recipients; primarily due to antibody-mediated rejections. Cumulative incidence of graft loss was 7.5% at 5 years and overall incidence of death was 6.07%.

Conclusion

Replacement of filtered plasma by donor group fresh frozen plasma rather than albumin reduced bleeding, IVIG administration, number of plasmapheresis sessions and the need for filters. Thymoglobulin avoidance decreased acute rejection rates. Rapid reduction and lower doses of prednisolone and MMF reduced infectious complications. These steps can help reduce rejection rates, complications and cost (up to USD 7000) comparable to ABO compatible transplantation in other centers as well.

As organ donation under DBD donors has reached a plateau in developed transplantation countries in Europe and the United States, organ donation after DCD donors has been actively promoted. This has led to the introduction of extracorporeal membrane oxygenation (ECMO) after cardiac arrest and withdrawal from life support when the patient is incapable of recovery, enabling the removal and transplantation of multiple organs after cardiac arrest. In Japan, these efforts have not been implemented, and only kidneys have been transplanted from DCD donors after spontaneous cardiac arrest. In addition, the revision of the Organ Transplant Law to allow organ donation under brain death with only family approval has drastically reduced the number of DCD donors. In Japan, efforts are underway to introduce ECMO and to wean patients off life support systems so that multi-organ donation after cardiac arrest will be possible as in Europe and the United States.

The global organ transplant activity remains satisfying less than 10% of the total number of patients in the waiting list. Brain dead donors and living donors have been the most common source of organs used worldwide. Nevertheless, as part of the different measures and policies implemented to increase donation, the use of donors after cardio-circulatory death (DCD), has been propitiated and expanded in the last couple of years. In Europe and North America, DCD programs had increased the number of available donors in up to 30%; but in many countries, the absence of DCD is mainly due to the lack of laws to legislate the process. We aim to report here the result of legal, ethical, procurement and specific organ working groups which met to assess the current regulatory framework, to evaluate the preliminary local experiences; and to produce a document to inform physicians and the community the current status of this program in our country.

Argentina, a pioneer country in procurement and donation has the regulatory and ethical frameworks to enable the transparent use and access to DCDs’, as well as its implantation for organs and tissues in the whole country. In spite of a very preliminary experience, we are proud to present that the process for using DCD has already started. But this novel process requires to be well understood and perceived by the general public and medical community. Education becomes essential.