32 research outputs found
Reply to:Balancing Cost and Efficiency in Screening Potential Organ Donors With Whole Body CT
Transplant surger
Complement Is Activated During Normothermic Machine Perfusion of Porcine and Human Discarded Kidneys
Background: The gap between demand and supply of kidneys for transplantation
necessitates the use of kidneys from extended criteria donors. Transplantation of these
donor kidneys is associated with inferior results, reflected by an increased risk of delayed
graft function. Inferior results might be explained by the higher immunogenicity of
extended criteria donor kidneys. Normothermic machine perfusion (NMP) could be
used as a platform to assess the quality and function of donor kidneys. In addition, it
could be useful to evaluate and possibly alter the immunological response of donor
kidneys. In this study, we first evaluated whether complement was activated during NMP
of porcine and human discarded kidneys. Second, we examined the relationship between
complement activation and pro-inflammatory cytokines during NMP. Third, we assessed
the effect of complement activation on renal function and injury during NMP of porcine
kidneys. Lastly, we examined local complement C3d deposition in human renal biopsies
after NMP.
Methods: NMP with a blood-based perfusion was performed with both porcine and
discarded human kidneys for 4 and 6 h, respectively. Perfusate samples were taken every
hour to assess complement activation, pro-inflammatory cytokines and renal function.
Biopsies were taken to assess histological injury and complement deposition.
Results: Complement activation products C3a, C3d, and soluble C5b-9 (sC5b-9) were
found in perfusate samples taken during NMP of both porcine and human kidneys. In
addition, complement perfusate levels positively correlated with the cytokine perfusate
levels of IL-6, IL-8, and TNF during NMP of porcine kidneys. Porcine kidneys with high
sC5b-9 perfusate levels had significantly lower creatinine clearance after 4 h of NMP. In line with these findings, high complement perfusate levels were seen during NMP of
human discarded kidneys. In addition, kidneys retrieved from brain-dead donors had
significantly higher complement perfusate levels during NMP than kidneys retrieved from
donors after circulatory death.
Conclusion: Normothermic kidney machine perfusion induces complement activation in
porcine and human kidneys, which is associated with the release of pro-inflammatory
cytokines and in porcine kidneys with lower creatinine clearance. Complement inhibition
during NMP might be a promising strategy to reduce renal graft injury and improve graft
function prior to transplantation
Donor diabetes mellitus is a risk factor for diminished outcome after liver transplantation:a nationwide retrospective cohort study
BACKGROUND: With the growing incidence of diabetes mellitus (DM), an increasing number of organ donors with DM can be expected. We sought to investigate the association between donor DM with early post-transplant outcomes. METHODS: From a national cohort of adult liver transplant recipients (1996-2016), all recipients transplanted with a liver from a DM donor (n=69) were matched 1:2 with recipients of livers from non-DM donors (n=138). The primary end-point included early post-transplant outcome, such as the incidence of primary non-function (PNF), hepatic artery thrombosis (HAT), and 90-day graft survival. Cox regression analysis was used to analyze the impact of donor DM on graft failure. RESULTS: PNF was observed in 5.8% of grafts from DM donors versus 2.9% of non-DM donor grafts (p=0.31). Recipients of grafts derived from DM donors had a higher incidence of HAT (8.7% vs. 2.2%, p=0.03) and decreased 90-day graft survival (88.4% [70.9-91.1] vs. 96.4% [89.6-97.8], p=0.03) compared to recipients of grafts from non-DM donors. The adjusted hazard ratio for donor DM on graft survival was 2.21 (1.08-4.53, p=0.03). CONCLUSION: Donor DM is associated with diminished outcome early after liver transplantation. The increased incidence of HAT after transplantation of livers from DM donors requires further research
Improving outcomes for donation after circulatory death kidney transplantation:Science of the times
The use of kidneys donated after circulatory death (DCD) remains controversial due to concerns with regard to high incidences of early graft loss, delayed graft function (DGF), and impaired graft survival. As these concerns are mainly based on data from historical cohorts, they are prone to time-related effects and may therefore not apply to the current timeframe. To assess the impact of time on outcomes, we performed a time-dependent comparative analysis of outcomes of DCD and donation after brain death (DBD) kidney transplantations. Data of all 11,415 deceased-donor kidney transplantations performed in The Netherlands between 1990-2018 were collected. Based on the incidences of early graft loss, two eras were defined (1998-2008 [n = 3,499] and 2008-2018 [n = 3,781]), and potential time-related effects on outcomes evaluated. Multivariate analyses were applied to examine associations between donor type and outcomes. Interaction tests were used to explore presence of effect modification. Results show clear time-related effects on posttransplant outcomes. The 1998-2008 interval showed compromised outcomes for DCD procedures (higher incidences of DGF and early graft loss, impaired 1-year renal function, and inferior graft survival), whereas DBD and DCD outcome equivalence was observed for the 2008-2018 interval. This occurred despite persistently high incidences of DGF in DCD grafts, and more adverse recipient and donor risk profiles (recipients were 6 years older and the KDRI increased from 1.23 to 1.39 and from 1.35 to 1.49 for DBD and DCD donors). In contrast, the median cold ischaemic period decreased from 20 to 15 hours. This national study shows major improvements in outcomes of transplanted DCD kidneys over time. The time-dependent shift underpins that kidney transplantation has come of age and DCD results are nowadays comparable to DBD transplants. It also calls for careful interpretation of conclusions based on historical cohorts, and emphasises that retrospective studies should correct for time-related effects
A nationwide evaluation of deceased donor kidney transplantation indicates detrimental consequences of early graft loss
Early graft loss (EGL) is a feared outcome of kidney transplantation. Consequently, kidneys with an anticipated risk of EGL are declined for transplantation. In the most favorable scenario, with optimal use of available donor kidneys, the donor pool size is balanced by the risk of EGL, with a tradeoff dictated by the consequences of EGL. To gauge the consequence of EGL we systematically evaluated its impact in an observational study that included all 10,307 deceased-donor kidney transplantations performed in The Netherlands between 1990 and 2018. Incidence of EGL, defined as graft loss within 90 days, in primary transplantation was 8.2% (699/8,511). The main causes were graft rejection (30%), primary nonfunction (25%), and thrombosis or infarction (20%). EGL profoundly impacted short- and long-term patient survival (adjusted hazard ratio; 95% confidence interval: 8.2; 5.1-13.2 and 1.7; 1.3-2.1, respectively). Of the EGL recipients who survived 90 days after transplantation (617/699) only 440 of the 617 were relisted for re-transplantation. Of those relisted, only 298 were ultimately re-transplanted leading to an actual re-transplantation rate of 43%. Noticeably, re-transplantation was associated with a doubled incidence of EGL, but similar long-term graft survival (adjusted hazard ratio 1.1; 0.6-1.8). Thus, EGL after kidney transplantation is a medical catastrophe with high mortality rates, low relisting rates, and increased risk of recurrent EGL following re-transplantation. This implies that detrimental outcomes also involve convergence of risk factors in recipients with EGL. The 8.2% incidence of EGL minimally impacted population mortality, indicating this incidence is acceptable
Whole Body CT Imaging in Deceased Donor Screening for Malignancies
Background. In most western countries, the median donor age is increasing. The incidence of malignancies in older
populations is increasing as well. To prevent donor-derived malignancies we evaluated radiologic donor screening in a retrospective donor cohort. Methods. This study analyzes the efficacy of a preoperative computed tomography (CT) scan
on detecting malignancies. All deceased organ donors in the Netherlands between January 2013 and December 2017
were included. Donor reports were analyzed to identify malignancies detected before or during organ procurement. Findings
between donor screening with or without CT-scan were compared. Results. Chest or abdominal CT-scans were performed in 17% and 18% of the 1644 reported donors respectively. Screening by chest CT-scan versus radiograph resulted
in 1.5% and 0.0% detected thoracic malignancies respectively. During procurement no thoracic malignancies were found in
patients screened by chest CT compared with 0.2% malignancies in the radiograph group. Screening by abdominal CT-scan
resulted in 0.0% malignancies, compared with 0.2% in the abdominal ultrasound group. During procurement 1.0% and 1.3%
malignancies were found in the abdominal CT-scan and ultrasound groups, respectively. Conclusions. Screening by
CT-scan decreased the perioperative detection of tumors by 30%. A preoperative CT-scan may be helpful by providing additional information on (aberrant) anatomy to the procuring or transplanting surgeon. In conclusion, donor screening by CT-scan
could decrease the risk of donor-derived malignancies and prevents unnecessary procurements per year in the Netherlands
Hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy: HARP-trial
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88436.pdf (publisher's version ) (Open Access)BACKGROUND: Transplantation is the only treatment offering long-term benefit to patients with chronic kidney failure. Live donor nephrectomy is performed on healthy individuals who do not receive direct therapeutic benefit of the procedure themselves. In order to guarantee the donor's safety, it is important to optimise the surgical approach. Recently we demonstrated the benefit of laparoscopic nephrectomy experienced by the donor. However, this method is characterised by higher in hospital costs, longer operating times and it requires a well-trained surgeon. The hand-assisted retroperitoneoscopic technique may be an alternative to a complete laparoscopic, transperitoneal approach. The peritoneum remains intact and the risk of visceral injuries is reduced. Hand-assistance results in a faster procedure and a significantly reduced operating time. The feasibility of this method has been demonstrated recently, but as to date there are no data available advocating the use of one technique above the other. METHODS/DESIGN: The HARP-trial is a multi-centre randomised controlled, single-blind trial. The study compares the hand-assisted retroperitoneoscopic approach with standard laparoscopic donor nephrectomy. The objective is to determine the best approach for live donor nephrectomy to optimise donor's safety and comfort while reducing donation related costs. DISCUSSION: This study will contribute to the evidence on any benefits of hand-assisted retroperitoneoscopic versus standard laparoscopic donor nephrectomy. TRIAL REGISTRATION: Dutch Trial Register NTR1433
A nationwide evaluation of deceased donor kidney transplantation indicates detrimental consequences of early graft loss
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