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"Kessaris, Nicos"
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Post-listing survival for highly sensitised patients on the UK kidney transplant waiting list: a matched cohort analysis
2017
More than 40% of patients awaiting a kidney transplant in the UK are sensitised with human leucocyte antigen (HLA) antibodies. Median time to transplantation for such patients is double that of unsensitised patients at about 74 months. Removing antibody to perform an HLA-incompatible (HLAi) living donor transplantation is perceived to be high risk, although patient survival data are limited. We compared survival of patients opting for an HLAi kidney transplant with that of similarly sensitised patients awaiting a compatible organ.
From the UK adult kidney transplant waiting list, we selected crossmatch positive living donor HLAi kidney transplant recipients who received their transplant between Jan 1, 2007, and Dec 31, 2013, and were followed up to Dec 31, 2014 (end of study). These patients were matched in a 1:4 ratio with similarly sensitised patients cases listed for a deceased-donor transplant during that period. Data were censored both at the time of transplantation (listed only), and at the end of the study period (listed or transplant). We used Kaplan-Meier curves to compare patient survival between HLAi and the matched cohort.
Of 25 518 patient listings, 213 (1%) underwent HLAi transplantation during the study period. 852 matched controls were identified, of whom 41% (95% CI 32–50) remained without a transplant at 58 months after matching. We noted no difference in survival between patients who were in the HLAi group compared with the listed only group (log rank p=0·446), or listed or transplant group (log rank p=0·984).
Survival of sensitised patients undergoing HLAi in the UK is comparable with those on dialysis awaiting a compatible organ, many of whom are unlikely to be have a transplant. Choosing a direct HLAi transplant has no detrimental effect on survival, but offers no survival benefit, by contrast with similar patients studied in a North American multicentre cohort.
UK National Health Service Blood & Transplant and Guy's & St Thomas' National Institute for Health Research Biomedical Research Centre.
Journal Article
Long-Term Outcomes of Pediatric Kidney Transplants From DCD and DBD Donors: A Comparative OPTN Study
2025
We compared the long-term outcomes of pediatric kidney transplants from DCD and DBD donors over a 33-year period in the USA. Data were retrieved and analysed on kidney transplants from deceased donors in paediatric recipients in 1994–2020 from the OPTN. Data were compared between those receiving kidney transplants from DBD and DCD donors. There were 11,071 paediatric kidney transplants from deceased donors including 350 from DCD donors. DCD transplants were more likely to have delayed allograft function (20.1% vs. 11.9%, p < 0.01). However, there was no significant difference in allograft or patient survival between transplants from DBD and DCD donors at 10 years (56% vs. 55%, p = 0.76 and 90% vs. 91%, p = 0.89). We describe the largest cohort of pediatric DCD kidney transplant recipients in the literature. We showed that despite higher rates of delayed allograft function in DCD transplants, long-term outcomes were not significantly different. Kidney transplants from DCD donors are a viable option and should be offered to children comparable to DBD kidneys as their long-term outcomes do not differ. DCD transplantation is illegal in some countries, however, it offers an opportunity to increase the number of transplants for children; this data should be considered in ongoing policy discussions.
Journal Article
Living Donation and Pre-Emptive Transplantation Are More Important Than HLA Matching in Pediatric Kidney Transplantation: Results From a 33-Year Comparative OPTN Study
by
Stojanovic, Jelena
,
Kessaris, Nicos
,
Kostakis, Ioannis D.
in
Adolescent
,
Allografts
,
Antigens
2025
Poorly HLA matched transplants have poorer long-term outcomes, however it is unclear whether living donation or pre-emptive transplantation can counteract the effects of HLA mismatches. We reviewed the long-term outcomes of paediatric kidney transplants with different HLA matches and aimed to identify other factors which may contribute significantly to long-term outcomes. We conducted a retrospective registry analysis of all pediatric kidney transplants from 1987–2020 in the USA from the OPTN Registry. These were analysed by HLA mismatches and compared by pre-transplant dialysis status and donor type. 21,500 patients were included for analysis. Overall, patients with unfavourable HLA matches had higher rates of delayed allograft function and lower allograft survival. However, patients with unfavourable HLA matched transplants from living donors had better allograft survival than patients with favourable HLA matched transplants from deceased donors (79% at 5 years vs. 71%, p < 0⋅01). Patients with pre-emptive unfavourable HLA matched transplants had better allograft and patient survival than patients with non-pre-emptive favourable HLA matched transplants (83% at 5 years vs. 78%, p = 0⋅02% and 98% vs. 96%, p < 0⋅01 respectively). In conclusion, living donation and pre-emptive transplantation have a more significant impact on clinical outcomes and lead to better allograft and patient survival than HLA matching.
Journal Article
Characteristics of Early Antibody Mediated Rejection in Antibody Incompatible Living Donor Kidney Transplantation
by
Kessaris, Nicos
,
Shaw, Olivia
,
Ibrahim, Maria
in
ABO Blood-Group System - immunology
,
ABOi
,
Adult
2024
Antibody incompatible transplantation (AIT) may be an only option for highly sensitized patients. Severe form of early antibody mediated rejection (AMR) adversely affects graft survival after AIT. The aim of this study was to identify individuals at risk of AMR. We analyzed 213 living donor AITs performed at our center. Among 120 ABOi, 58 HLAi and 35 DSA + FCXM-negative cases, the rates of early AMR were 6%, 31%, and 9%, respectively (
p
< 0.001). On multivariate analysis for graft loss, early AMR had a HR of 3.28 (
p
< 0.001). The HLAi group had worse death-censored graft survival (
p
= 0.003). In the HLAi group, Patients with aggressive variant AMR (AAMR) had greater percentage of C3d complement fixing DSA, higher baseline class I and total DSA MFI levels and B-cell FCXM RMF. C1q and C3d complement fixing DSA and strong positivity of baseline B- or T-cell FXCM as predictors of AAMR had 100% sensitivity. Early AMR is of significant clinical concern in AIT as it results in poor graft survival and is not well described in literature. An aggressive variant is characterized by massive rise in DSA levels at rejection. Baseline DSA, C1q, and C3d and baseline FCXM values can be used to risk-stratify candidates for AIT.
Journal Article
Clinical Outcomes and Quality of Life of Patients Receiving Multi-Solid-Organ Transplants in Childhood Are Excellent: Results From a 20-Year Cohort Study
2024
Advances in medicine allow children with previously fatal conditions to survive longer and present as transplant candidates; some requiring multiple solid-organ transplants (MSOT). There is limited data on clinical outcomes and no data on quality of life (QoL). In this mixed methods cohort study clinical outcomes from the NHSBT registry were analysed for all patients who received a kidney and one other solid-organ transplant as a child between 2000 and 2021 in the UK. QoL was measured using the PedsQL 3.0 Transplant Module questionnaire. 92 children met the inclusion criteria: heart/heart-lung and kidney (n = 15), liver and kidney (n = 72), pancreas and kidney (n = 4) and multivisceral (n = 1). Results showed excellent patient and graft survival, comparable to single-organ transplants. Allograft survival and rejection were significantly better in patients with combined liver and kidney transplants compared to patients with sequential liver and kidney transplants. QoL was excellent with a mean score of 74%. Key findings included a significant improvement in QoL post-transplant. This is the first study to look at clinical and QoL outcomes in MSOT recipients. The results indicate excellent long-term outcomes. All children born with conditions leading to end-stage disease in multiple solid-organs should be assessed as transplant candidates.
Journal Article
Early relapse of atypical hemolytic uremic syndrome following ABO-incompatible living–related pediatric kidney re-transplant successfully treated with eculizumab
by
Kessaris Nicos
,
Stojanovic Jelena
,
Marks, Stephen D
in
ABO system
,
Autoantibodies
,
Blood groups
2021
BackgroundA 3-year-old girl with clinical features of atypical HUS (complement Factor I mutation inherited from an asymptomatic mother and Factor H autoantibodies) was treated with plasma exchange, progressed to kidney failure (KF) aged 4 years, and received an en bloc kidney DCD transplant aged 8 years with primary graft non-function necessitating transplant nephrectomy at the time of transplantation. She subsequently underwent re-transplantation from her father. This is a retrospective study of electronic patient records and medical notes.Case–Diagnosis/TreatmentA 9-year-old girl received an ABO-incompatible (ABOi) living–related kidney transplant from her father with recipient and donor blood groups of O and A, respectively, with baseline recipient anti-A titers 1:128 reducing to 1:4 at the time of transplant with B lymphocyte depletion with rituximab and four sessions of immunoadsorption. Six hours post-transplant, she had recurrence of aHUS and received the first dose of eculizumab. She continues on monthly home eculizumab infusions with stable kidney allograft function and negative anti-A titers 7 years post-kidney transplantation.ConclusionsThis is the first report of a pediatric high-risk ABOi living–related kidney transplantation in whom early relapse of aHUS was successfully treated with eculizumab with good long-term patient and allograft outcome.
Journal Article
Outcomes of paediatric kidney transplant recipients using the updated 2013/2017 Banff histopathological classification for antibody-mediated rejection
2021
BackgroundAfter the major changes with regard to acute and chronic ABMR in the Banff classification initiated in 2013, there has been an improvement in diagnosing antibody-mediated rejection (ABMR) in adult studies but no data have been published in the paediatric population.MethodsWe assessed 56 paediatric kidney transplant biopsies due to kidney dysfunction in patients with donor-specific antibodies (DSA) in a retrospective single-centre study between January 2006 and March 2012. The results were compared with 2003/2007 Banff classification noting the subsequent 2017 and 2019 modifications do not change the 2013 Banff classification with regard to acute antibody-mediated rejection (apart from the addition of gene transcripts/classifiers that do not affect our analysis).ResultsFollowing the 2013 Banff classification, there were seven cases (12.5%) diagnosed with ABMR that would have been misclassified when applying the 2003/2007 classification. Evaluating the histological features of all ABMR-related cases, we report the importance of v− (intimal arteritis) and t− (tubulitis) lesions: absence of v− and t− lesions in the biopsy is related to significantly higher kidney allograft survival (OR 7.3, 95%CI 1.1–48.8, p = 0.03 and OR 5.3, 95%CI 1.2–25.5, p = 0.04 respectively). Moreover, absence of t− lesions was associated with significantly fewer rejection episodes the year after the initial biopsy (OR 5.1, 95%CI 1.4–19.8, p = 0.01).ConclusionsOur study supports that the updated 2013 Banff classification shows superior clinicopathological correlation in identifying ABMR in paediatric kidney transplant recipients. Our results can be extrapolated to the recently updated 2019 Banff classification.
Journal Article
Online versus in‐person surgical near‐peer teaching in undergraduate medical education during the COVID‐19 pandemic: A mixed‐methods study
2024
Background and Aims
The coronavirus disease 2019 (COVID‐19) pandemic stimulated a paradigm shift in medical and surgical education from in‐person teaching to online teaching. It is unclear whether an in‐person or online approach to surgical teaching for medical students is superior. We aim to compare the outcomes of in‐person versus online surgical teaching in generating interest in and improving knowledge of surgery in medical students. We also aim the quantify the impact of a peer‐run surgical teaching course.
Methods
A six‐session course was developed by medical students and covered various introductory surgical topics. The first iteration was offered online to 70 UK medical students in March 2021, and the second iteration was in‐person for 20 students in November 2021. Objective and subjective knowledge was assessed through questionnaires before and after each session, and also for the entire course. Data were analyzed from this mixed‐methods study to compare the impact of online versus in‐person teaching on surgical knowledge and engagement.
Results
Students in both iterations showed significant improvement of 33%–282% across the six sessions in knowledge and confidence after completing the course (p < 0.001). There was no significant difference in the level of objective knowledge, enjoyment, or organization of the course between online and in‐person groups, although the in‐person course was rated as more engaging (mean Likert score 9.1 vs. 9.7, p = 0.033).
Discussion
Similar objective and subjective surgical teaching outcomes were achieved in both iterations, including in “hands‐on” topics such as suturing, gowning, and gloving. Students who completed the online course did not have any lower knowledge or confidence in their surgical skills; however, the in‐person course was reported to be more engaging. Surgical teaching online and in‐person may be similarly effective and can be delivered according to what is most convenient for the circumstances, such as in COVID‐19.
Journal Article
Multicentre randomised controlled trial: protocol for Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO)
2022
IntroductionAcute electrolyte and acid–base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor kidney, the majority of which are from living and deceased adult donors. Hypotonic intravenous fluid is commonly used in the post-transplant period due to clinicians’ concerns about the sodium, chloride and potassium content of isotonic alternatives when administered in large volumes.Plasma-Lyte 148 is an isotonic, balanced intravenous fluid that contains sodium, chloride, potassium and magnesium with concentrations equivalent to those of plasma. There is a physiological basis to expect that Plasma-Lyte 148 will reduce the incidence of clinically significant electrolyte and acid–base abnormalities in children following kidney transplantation compared with current practice.The aim of the PLUTO trial is to determine whether the incidence of clinically significantly abnormal plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte-148 compared to intravenous fluid currently administered.Methods and analysisPLUTO is a pragmatic, open-label, randomised controlled trial comparing Plasma-Lyte 148 to current care in paediatric kidney transplant recipients, conducted in nine UK paediatric kidney transplant centres.A total of 144 children receiving kidney transplants will be randomised to receive either Plasma-Lyte 148 (the intervention) intraoperatively and postoperatively, or current fluid. Apart from intravenous fluid composition, all participants will receive standard clinical transplant care.The primary outcome measure is acute hyponatraemia in the first 72 hours post-transplant, defined as laboratory plasma sodium concentration of <135 mmol/L. Secondary outcomes include symptoms of acute hyponatraemia, other electrolyte and acid–base imbalances and transplant kidney function.The primary outcome will be analysed using a logistic regression model adjusting for donor type (living vs deceased donor), patient weight (<20 kg vs ≥20 kg pretransplant) and transplant centre as a random effect.Ethics and disseminationThe trial received Health Research Authority approval on 20 January 2020. Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain.Trial registration numbers2019-003025-22 and 16586164.
Journal Article
Psychological Concerns of Children Undergoing Kidney Transplantation During the Pandemic: Single-centre Experience
by
Stojanovic, Jelena
,
Kessaris, Nicos
,
Marks, Stephen
in
Audit departments
,
Child
,
Coronaviruses
2021
Many paediatric kidney transplant programmes were closed during the COVID-19 pandemic, and due to the vulnerable nature of patients with end-stage kidney disease (ESKD), there were new concerns once these programmes reopened. We surveyed children and families who received a kidney transplant during the pandemic. We found that half of the participants felt scared and/or anxious about receiving a kidney transplant during the pandemic, and 2/8 participants were worried about catching COVID-19 during their recovery. While detailed counselling and additional safety precautions contributed to a good experience, patients and parents still demonstrated fear towards transplantation.
Journal Article