Transplantation Reports最新文献

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.

Background

Osteoporosis is a prevalent complication in heart transplant population. Denosumab is a monoclonal antibody that inhibits bone resorption approved for the treatment of corticosteroid-induced osteoporosis and potentially useful in heart transplant recipients.

Objective

To describe the metabolic and densitometric effects of denosumab in these patients, as well as the adverse effects observed.

Methods

We performed a study of 9 transplant patients between 2014 and 2019 who were treated with denosumab for osteopenia or osteoporosis. All patients received postoperative calcium and vitamin D supplements. We measured the changes in densitometric and metabolic variables and compared them by Student's t-test.

Results

After therapy, bone mineral density (BMD) and Tscore at lumbar spine improved a mean of 0.0458 and 0.5000, respectively (p < 0.05). The mean increase of BMD was 6.09% at lumbar spine and 7.84% at femoral neck. There was a case of abrupt decrease of BMD at total hip. A decrease in magnesium levels was observed after a dose of denosumab (p < 0.05), which included 1 case of hypomagnesemia. There were 2 cases of hypophosphatemia, and none of hypocalcaemia. 77.78% of the patients had infections, one of them serious.

Conclusion

Denosumab was shown to improve BMD at lumbar spine and could be a valid alternative for the treatment of osteoporosis in heart transplant patients. The risk of hypocalcaemia could be minimized with calcium adjustment prior to starting treatment. More studies are needed to assess its effects and the risk of infections.

Introduction

Since the beginning of pancreas transplantation, the rate of donation after cardiac (or circulatory) death (DCD) accounts for only 3% of all transplants in the US. This is the result of perceived higher complication rates and overall worse outcome with DCD donors. Such misconceptions and an increased demand for deceased donor (DD) organs warrant a systematic review of the use of DCD compared with donation after brain death (DBD) pancreata to objectively assess DCD outcome after pancreas transplantation in the US.

Methods

All 22,160 DD pancreas transplants performed in diabetic patients between 1/1/2001 and 12/31/2020 were included in this analysis. To assess changes in outcomes, patient and graft survival was computed using the Kaplan-Meier method in 5-year intervals. Comprehensive univariate and multivariable comparisons of posttransplant complications and patient and pancreas and kidney graft survival between DCD and DBD pancreas transplants were performed to assess the donor impact.

Results

In the US over the past 20 years most DCD donors were used for simultaneous pancreas and kidney (SPK) transplants and less often for solitary pancreas transplants. DCD transplants never accounted for more than 4% per year of all pancreas transplants. A comparison of the pancreas donor risk index (pDRI) between DCD and DBD pancreata showed that the only distinguishing factor was DCD donation. SPK patient, pancreas, and kidney graft survival for DCD donors did not change significantly over time. One- and 3 -year DCD patient survival reached 96% and 93%, pancreas graft survival 90% and 84%, and kidney graft survival 96% and 91%, respectively. For the last decade, no differences in patient and graft survival between DCD and DBD donors were detected (P > 0.67). The relative risk for the use of a DCD donor was not increased (P > 0.6). Influential risk factors were older donor and recipient age as well as longer preservation times. Larger transplant center accepted DCD donors more frequently and showed better outcome. While the rate of early pancreas complications was the same for DCD vs. DBD transplants, delayed kidney graft function was significantly higher in DCD kidneys secondary to more long-distance shipping across the country. The multivariable analysis showed a 4-times higher rate in delayed graft function. Longer cold preservation time and older donor age further increased the risk of graft failure. The use of machine perfusion of the kidney graft reduced the relative risk of delayed graft function by 50%.

Summary

The use of DCD donor organs in pancreas transplantation is not associated with higher failure or complication rates in the US. A pancreas offer from a DCD donor should not be the sole reason to decline the organ for transplantation. Careful selection of specific donor and recipient factors, as well as advanced pr