Transplantation Reports最新文献

Introduction

Donation after cardiac death (DCD) has been leading the way to help bridge the growing gap between availability of donors and recipients on waitlist. With advances in technology and our understanding of DCD donation the safety profile is growing. It is becoming an increasing viable option even in marginal settings.

Discussion

The ethos surroundings DCD is still a matter of contention but there is support and collaboration from larger societies and establishments with development of standardizing protocols. Preparation is key. Experience of the procurement and transplanting surgeons are pivotal. There are multiple moving parts and for the success of a DCD program, dedication is needed from the donor hospitals, organ procurement organizations and the transplant centers. Previous practices based on anecdotal experiences are now either supported by or refuted by increasing evidence and data, based on the development of consensus-based guidelines with the end goal of having uniform outcomes. Normothermic regional and machine perfusion have expanded options in the DCD world, challenging the limits and expanding our paradigm. Recognition of the weaknesses and organ specific complications allow the clinician to make choices for optimal outcomes. These advancements have allowed outcomes to be optimized.

Conclusions

Expanding the organ donor pool is one solution to increase the availability of organs for transplantation. Increasing the attention to and the use of DCD organs combined with machine and normothermic perfusion is a future strategy to obtain ongoing clinical success in organ transplantation and lower the waiting list mortality.

Tissue and organ transplantation is the best treatment option for end-stage organ failure. However, organ shortage still remains to be the greatest challenge facing the field of organ transplantation. Millions of people die and are buried with healthy organs, which could save the lives of many patients who continue to wait on transplant lists. Countries must aim to work towards a system of matching organs as much as possible with the deceased donation to meet the growing demand for organs. This action will not only result in the reduction of organ trafficking activities but shall also make an enormous difference to those patients awaiting transplants where living organ donors are not an option.

Donation after circulator death (DCD) has gained much attention over the last decade as one of the accepted practices in order to expand the donor pool. DCD donation takes place after declaration of death using cardio-respiratory criteria in contrast to donation after brain death (DBD) where neurological criteria are used. Although DCD remains a focus of interest and contributes to donor numbers in many countries, it also poses many challenges medically, ethically and legally. Unfortunately, controlled DCD is not really in practice in Turkey and the Middle East.

Therefore, the purpose of this review is to provide an overview of current status of DCD in Turkey and the Middle East and to identify associated concerns medically and ethically.

Diabetes mellitus is a major cause of morbidity and mortality worldwide. Pancreas transplantation has evolved into a viable treatment option in this patient population. While the majority of procedures are performed as either simultaneous pancreas-kidney (SPK) or pancreas after kidney (PAK), the resulting glycemic control leads to a significant delay in the progression of cardiovascular disease. At present, there is a critical organ shortage. Donation after circulatory death (DCD) may be a strategy to increase the pancreas donor pool. Herein, we examine the clinical parameters that impact organ selection and review the current experience with pancreas transplantation in the setting of DCD donation.

Livers procured from donors after circulatory death (DCD) have increasingly been used for liver transplantation (LT) to address the organ crisis. While DCD LT increases patient access to life-saving treatment, this practice creates risks for recipients, including primary allograft non-function, early allograft dysfunction, and ischemic cholangiopathy. These complications are due to the unique ischemia and reperfusion injury related to different phases of organ procurement and preservation in DCD. Therefore, substantial research efforts and innovations on DCD LT have primarily aimed at reducing these complications. One such advance is the utilization of ex vivo machine perfusion of the donor liver in DCD LT. This review focused on the data from clinical trials and studies in human DCD LT.

Human immunodeficiency virus infection was traditionally considered an absolute contraindication for transplantation because of the concern that immunosuppression would accelerate HIV disease progression, resulting in increased mortality and a "waste" of organs. Since potent antiretroviral therapy became widely available in 1996, the prognosis of patients with HIV infection has dramatically improved. HIV-infected patients are now accepted recipients of both HIV-infected and HIV- uninfected donor organs in specialized transplant centers worldwide. However, due to stigma about the disease and lack of appropriate expertise, renal transplant in HIV patients has not been done in Nepal. Here, we report the first case of renal transplantation done in patient with HIV in Nepal. So, even in a resource limited setting like Nepal, HIV-positive ESRD patients with stable disease should be given the benefit of kidney transplantation as patient and graft survival are reasonably good with better quality of life.

Background

It is imperative to increase the donor pool due to a persistent shortfall of organs for transplantation. Therefore, organ donation after circulatory death (DCD) was reintroduced in Taiwan in 2017, and has become a rightful source for kidney and liver transplantation. We aim to report the preliminary outcomes of organ transplantation from DCD donors in Taiwan.

Methods

All data of 48 DCD donors and consecutively 106 grafts were obtained from the registry of Taiwan Organ Registry and Sharing Center. Kidney and liver transplantations were performed between Jan 5th, 2018 and Sep 24th, 2021. The primary endpoints were recipient survival and graft survival by using Kaplan-Meier method.

Results

Overall, DCD donors accounted for 9.6% (48/501) of all deceased donors in Taiwan from 2017 to 2021. The recipient survival for 3-month, 1-year, and 3-year were 99, 94, and 94% for DCD kidney transplants; 86, 76 and 76% for DCD liver transplants. The 3-month and three-year kidney graft survival (censored for death) reached 95% and 94%, respectively; while liver graft survival (censored for death) reached 95% and 89%, respectively.

Conclusions

Transplantations from DCD donors showed satisfactory graft and recipient survivals in both kidney and liver transplants. Both kidney and liver transplantation from potential DCD donors should be advocated for its comparable outcomes to organs from brain-dead deceased donors.

Background

Chronic lung allograft dysfunction (CLAD) is a highly prevalent and devastating complication in lung transplant (LT), culminating in increased allograft failure, morbidity, and mortality. Determination of the fraction of plasma donor-derived cell-free DNA (dd-cfDNA) has emerged as a valuable noninvasive monitoring tool after LT; however, the increased variance of host cfDNA caused by infection and other inflammation can complicate the approach.

Methods

In a retrospective pilot study, we analyzed both the fraction of dd-cfDNA (%dd-cfDNA) and absolute quantity of dd-cfDNA (cp/mL) in recipients with CLAD ≥ 5-year post-LT with co-morbid conditions (gastro-esophageal reflux, antibody-mediated rejection, or chronic infection) designated as complicated (C-CLAD) and uncomplicated (U-CLAD) cohorts.

Results

Median time post-LT was 2,149 days (1,899-2,920). The median %dd-cfDNA for the C-CLAD (N=5) cohort was 1.79% (IQR: 1.04-2.29) and significantly elevated compared to the U-CLAD cohort (N=7, 0.49%; 0.28-0.88) (p=0.018). Absolute dd-cfDNA was also significantly higher in C-CLAD (43.2 cp/mL; 27.9-89.3) than the in U-CLAD cohort (19.6 cp/mL; 8.1-27.9) (p=0.048).

Conclusions

We report a heretofore undescribed dichotomy of dd-cfDNA levels with CLAD ≥ 5-years, related specifically to elevation in allograft quantity as opposed to alteration in host plasma cfDNA. Further, dd-cfDNA analysis in association with co-morbid conditions in C-CLAD may offer insights for potential treatment and alleviation of molecular injury. Measurement of longitudinal absolute quantity dd-cfDNA may provide additional value for future clinical study design of pathobiology and CLAD treatment algorithms.

Introduction

We conducted a prospective validation study at Cincinnati Children's Hospital Medical Center and Ohio State University Medical Center to test if absolute CD38 bright CD8+TEM cells > 30/µL would predict acute GVHD, similar to our pilot data.

Methods

Blood was collected twice weekly following HSCT. If CD38 bright CD8+ TEM ≥ 30 cells/µL, Epstein-Barr virus and cytomegalovirus specificity was determined by tetramer staining, granzyme B content was assessed, Ki-67 staining performed to assess T-cell proliferation. Cells were incubated with alemtuzumab, daratumumab and cyclophosphamide in vitro to determine susceptibility to depletion.

Results

Of the 182 enrolled patients, 83 (45.6%) developed acute GVHD by day+100 but 171 patients were evaluable (acute GVHD n = 77 and no GVHD n = 94). There was no difference in the maximum absolute CD38 bright CD8+TEM cells prior to clinical symptoms and also after CMV and EBV tetramer positive patients were excluded from both cohorts. Ki-67 or Granzyme B expression in patients were comparable between patients with and without acute GVHD. Lastly CD38 bright CD8+ T-cells were effectively depleted with alemtuzumab and cyclophosphamide in vitro.

Conclusion

Absolute peripheral blood CD38 bright CD8+TEM cells ≥30 do not predict acute GVHD in a large validation cohort of adult and pediatric HSCT recipients.

Introduction: Chronic kidney disease (CKD) is one of the main burden for healthcare system not only in Kazakhstan. The number of patients with CKD increases annually. Among renal replacement approaches, kidney transplantation (KTx) is the best therapeutic option. KTx is performed in Kazakhstan since 2010. Various factor can either improve or deteriorate outcome after KTx. Here we analyzed factors, influencing graft survival. We have performed this study in order to detect the factors, that significantly affects the KTx outcomes, preferably from living donor

Methods: Clinical data of the 253 kidney recipients were collected from archives of National Research oncology center and retrospectively analyzed.

Results: Immunological status before KTx was found to affect outcome. The presence of HLA class I antibodies was significantly related to graft loss (p=0.046).Coexistence of HLA class II antibodies and the graft loss was not significant (p=0.324). Acute postoperative rejection was highly correlated with graft loss (p<0.001). Of the cohort, 18 (7%) had acute rejection, and 13 (72%) of them were women (p<0.001). The graft survival was statistically significantly related to the gender of the recipient with p=0.002. The 5-year survival of a graft in females was 80.2%, while for males it was 95.3%. In addition, post-operational complications remarkably influenced the graft loss with p=0.005

Conclusion: Recipients' gender, immunological status, and acute graft rejection episodes after transplantation were predictors of a worse kidney function 1 year after transplantation.

Background

Kidney transplantation between HLA matched siblings results in superior graft survival. It has been hypothesized that the degree of HLA matching in these cases reduces the risk of organ rejection, allowing for reduced immunosuppression exposure. Current tolerance protocols are successful in permitting immunosuppression withdrawal, but require initial exposure to high levels of immunosuppression. Long term data on immunosuppressive complications has not been well studied in this population, and are needed to fully evaluate current tolerance protocols.

Methods

In this retrospective cohort, we aimed to evaluate immunosuppression regimens among HLA-matched living kidney transplant recipients. We screened living kidney donor transplant donors-recipient pairs from 2013 to 2019 and found 28 recipients meeting criteria. A retrospective chart review using the electronic medical record was performed evaluating for preoperative clinical factors, cause of ESRD, maintenance immunosuppression regimen, short and long term sequelae of immunosuppression exposure as well as graft outcomes.

Results

Median age was 49, half were women and half were non-White (25% Hispanic, 14% Asian/Pacific Islander, 7% other and 4% African American). Median follow up was 3.5 years. Most common causes of ESRD were glomerulonephritis, diabetes and polycystic kidney disease. Over 80% of patients were on calcineurin inhibitor based dual therapy, with approximately 50% on prednisone and the remainder on an anti-metabolite. 14% of first time HLA matched kidney transplant recipients were on 3 immunosuppressive medications. 43% of recipients experienced immunosuppression-related complications, the most common of which was infection, occurring in almost a third of all patients. Graft and overall survival was 100% for this cohort with an average serum creatinine between 1.1 and 1.3 mg/dL at the end of the study period. One patient experienced acute rejection (4%).

Conclusions

In our single institution study, a large proportion of HLA matched living kidney transplant recipients experienced complications related to immunosuppression. The majority of patients were on CNI based therapy with a second agent. Additional studies are necessary to determine minimal effective dosing of immunosuppression in HLA matched living donor kidney transplants.