BackgroundPost-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation associated with long-term immunosuppression and Epstein–Barr virus (EBV) reactivation. This study analyses the clinical presentation, diagnostic pathways, therapeutic strategies and outcomes of PTLD in renal and pancreatic transplant recipients at the Manchester Centre for Transplantation.MethodsA retrospective cohort study was carried out on a cohort of 73 patients diagnosed with PTLD between 2002 and 2025 following renal, simultaneous pancreas-kidney (SPK) or pancreas-only transplantation. Data were collected from electronic medical records and analysed descriptively. Clinical presentations were categorised into organ system involvement. Time from presentation to diagnosis and survival outcomes were assessed.ResultsThe median time from transplant to PTLD diagnosis was 132 months, with 56% of cases diagnosed more than 10 years post-transplant. Monomorphic PTLD, in particular diffuse large B-cell lymphoma (DLBCL), was the most common subtype. EBV-positivity was seen in all early cases and in 57% overall. Abdominal and B symptoms were the most frequent presentations. Bleeding and/or anaemia were significantly associated with diagnostic delay (p = 0.045), and delays over one month were associated with reduced survival (p = 0.061). Complete or partial remission was achieved in 75% of patients. The 5-year overall survival rate was 68% while 1-year survival was 83% and death-censored graft survival was 82%.ConclusionIn our cohort, PTLD in transplant recipients presents with diverse symptoms and can occur several years post-transplant highlighting the need for long-term vigilance. Streamlined referral pathways and increased awareness could reduce diagnostic delays. Establishing a national PTLD registry would benefit future research.
Laparoscopic living donor nephrectomy, first carried out in 1995 by Lloyd Ratner, is now the established gold standard technique of donor nephrectomy globally and in the United Kingdom. Its minimally invasive nature with associated patient benefits, and concomitant excellent recipient outcomes underpin surgeon preference as the technique of choice in living kidney donation. There are 23 transplant centres in the United Kingdom currently offering laparoscopic donor nephrectomy. There are however variations in the laparoscopic approach amongst and within the different centres. These variations have evolved due to various centre-related factors, including local expertise, training, and the availability of specific instrumentation. This review discusses the five variations of laparoscopic donor nephrectomy currently offered in the United Kingdom. These techniques include: Totally laparoscopic donor nephrectomy (TLDN), hand-assisted laparoscopic donor nephrectomy (HALDN), Robotic-assisted donor nephrectomy (RADN), Hand assisted retroperitoneoscopic (HARP) donor nephrectomy and Laparoscopic retroperitoneal donor nephrectomy (RDN).
Introduction: We aimed to compare the efficacy of pancreas transplantation, islet transplantation, and insulin therapy in patients with type 1 diabetes mellitus (T1DM) undergoing renal transplantation. Methods: We conducted a systematic search across three databases on November 26, 2024 for studies on simultaneous pancreas-kidney transplant (SPKT), pancreas-after-kidney (PAK), simultaneous islet-kidney (SIK), islet-after-kidney (IAK), and kidney transplant alone with insulin (KTA-I) in T1DM. We analyzed changes in glycated hemoglobin (HbA1c %) from baseline, as well as other glucose metabolism, renal, and cardiovascular parameters. Pooled single means or mean differences (MD) were calculated with 95% confidence intervals (CIs). Overall survival (OS) and graft survival were assessed using the restricted mean survival time, derived from Kaplan-Meier curves at the truncated time. Results: We included 286 studies in the systematic review and 142 in the meta-analysis. We found that SPKT offers a greater reduction in HbA1c than KTA-I (MD:-3·2; CI:-5·26, -1·14) after 3 years. At 12 months, mean C-peptide (ng/mL) levels were higher after SPKT than after SIK/IAK (2·76 CI:2·49, 3·02 vs. 1·54 CI:0·16, 2·92). At 60 months after transplantation, OS was similar for SPKT, PAK, and KTA-I, whereas SIK/IAK was associated with the lowest OS (P=0·0095). At 120 months, overall and kidney graft survival were higher in LDK than DDK, and LDK was not inferior to SPKT. Pancreas graft survival was higher after SPKT than PAK (P=0·0018). Interpretation: Pancreas transplantation provides the best glucose metabolism. LDK offers higher graft survival than DDK and is comparable to SPKT, which in turn offers better pancreas graft survival than PAK. Islet transplantation is associated with the lowest OS.
BACKGROUND:The use of induction immunosuppression agents has improved kidney transplant outcomes, but selecting the optimal agent remains a point of debate. AIM:To compare the long-term outcomes of kidney transplant recipients receiving alemtuzumab vs basiliximab induction, focusing on graft function, acute rejection, infection, malignancy, post-transplant glomerulonephritis, and survival, using a propensity score matched cohort design. METHODS:Kidney transplant recipients who received alemtuzumab or basiliximab induction from 2014 to 2019 across two nephrology centres in Northwest England were evaluated. Propensity score matching at a 1:1.5 ratio ensured comparability between cohorts. Baseline characteristics, immunosuppression regimens, and outcomes were analyzed. Linear, binary logistics and Cox proportional hazard regression models. RESULTS:A total of 436 recipients were included, with a median follow-up of 5.2 years. The matched cohort (n = 262) had a mean age of 51.1 ± 13.5 years; 39% were female and 92% were white. There was no significant difference in the cumulative incidence of acute rejection [odds ratio (OR) = 2.10; 95%CI: 0.9-4.9; P = 0.110]. Compared with basiliximab, alemtuzumab was associated with lower estimated glomerular filtration rate at 12 months (-6.6 mL/minute/1.73 m2; 95%CI: -10.5 to -2.7; P < 0.001) and higher risks of cytomegalovirus viremia (OR = 3.2; 95%CI: 1.6-6.5; P < 0.001), BK viremia (OR = 2.4; 95%CI: 1.1-5.5; P = 0.02), post-transplant malignancy (OR = 6.2; 95%CI: 1.6-29.9; P = 0.013), and death-censored graft loss (hazard ratio = 3.6; 95%CI: 1.2-11.4; P = 0.03). No significant differences were observed in post-transplant glomerulonephritis or recipient mortality. CONCLUSION:In this propensity score-matched analysis, alemtuzumab induction was associated with lower graft function at 12 months and higher risks of viral infection, post-transplant malignancy, and graft loss compared with basiliximab. These findings highlight the need for further studies to confirm the long-term safety and effectiveness of alemtuzumab in kidney transplantation.
Kidney and islet transplantation has revolutionized the management of renal failure and diabetes. Transplantation is considered as excellent therapeutic intervention for most suitable patients. While advancements in the surgical aspects, immunosuppression and outcomes have potentially plateaued, new technologies have developed which could enhance transplantation with benefits to patients and clinical teams alike. The science of nanotechnology and big data advancements are two such technologies, collectively paving the way for smarter transplantation solutions. Nanotechnology offers novel strategies to overcome critical challenges, including organ preservation, ischemia-reperfusion injury and immune modulation. Innovations such as nanoparticle-based drug delivery systems, biocompatible encapsulation technologies for islet transplants, and implantable artificial kidneys are redefining the standards of care. Meanwhile, big data analytics harness vast datasets to optimize donor-recipient matching, refine predictive models for post-transplant outcomes, and personalize therapeutic regimens. Integrating these technologies forms a synergistic framework where nanotechnology enhances therapeutic precision and big data provides actionable insights, enabling clinicians to adopt proactive, patient-specific strategies. By addressing unmet needs and leveraging the combined potential of nanotechnology and big data, this transformative approach promises to improve graft survival, functionality, and overall patient outcomes, marking a paradigm shift in transplantation medicine. These developments will also be accelerated with integration of the rapidly advancing science of artificial intelligence.
Encapsulating peritoneal sclerosis (EPS) is a rare condition characterised by recurrent episodes of intestinal obstruction and perforation, usually due to prolonged peritoneal dialysis exposure, resulting in abdominal catastrophes often requiring open abdomen management (OAM). Dynamic negative pressure wound therapies (NPWTs) can facilitate definitive closure in the open abdomen, but consensus recommendations lack high-quality, cohort-specific data. We performed a retrospective analysis on the use of NPWTin this patient cohort to assess its effectiveness when compared to management with static management of the open abdomen. Primary endpoints assessed were: (i) definitive closure; (ii) time to definitive closure; and (iii) method of closure. Secondary endpoints included assessment of complications. Multiple linear and logistic regression analysis assessed variables predictive of primary endpoints. 99 patients were included. 43 (43%) patients were managed with NPWT and 56 (57%) patients with static mechanisms (betadine-soaked gauze.) Patients who were managed with NPWTwere more likely to achieve fascial closure (n=27 vs n=7, p<0.0001), required less total theatre episodes (n=2.27 vs 4.78, p<0.0001), and reported less failure to close episodes (p=0.002). The use of NPWTwas associated with fewer returns to theatre following closure within 30 days (n=4 vs n=19, p=0.004). Failure to close was associated with all-cause mortality (p<0.026). This study demonstrates that NPWT is associated with increased likelihood of fascial closure with a reduced complication profile in patients with EPS, representing a chronically malnourished, high-risk surgical cohort. NPWTshould be within the armamentarium of the general surgeon faced with a complex open abdomen and can be safely used in high-risk surgical patients.
Encapsulating peritoneal sclerosis (EPS) is a rare and potentially fatal complication of long-term peritoneal dialysis (PD). It also occurs idiopathically and in some inflammatory conditions. A characteristic fibro-collagenous membrane encases the bowel, leading to intestinal obstruction and malnutrition, and resulting in significant morbidity and mortality. Diagnosis is often made in the late stages. Despite its clinical importance, there are no standardised management guidelines for EPS globally. This systematic review evaluates management strategies described in the literature, assesses challenges and identifies patient-specific factors influencing treatment outcomes. A systematic search of PubMed and Web of Science was conducted using the keywords “Encapsulating peritoneal sclerosis” and “treatment”. This yielded 26 publications from 2014 to 2024, comprising 20 case reports and 6 case series, which were critically appraised using the Joanna Briggs Institute checklist. Data were analysed descriptively, focusing on the cohort’s baseline features, definitive treatment modalities, recurrence and outcomes. Among the 26 studies reviewed, we examined 589 patients. Of these, 134 (22.8%) were surgically managed with peritonectomies, adhesiolysis, jejunostomies, lavage, and resections. 76 (12.9%) patients were managed medically, incorporating corticosteroids, tamoxifen, and immunosuppressants. 219 (37.2%) were managed with a combination of both approaches and 160 (27.2%) were managed conservatively. EPS-related mortality was 22.2%. Outcomes varied on the disease stage, intervention timing, and the overall clinical condition of patients. This review highlights the complexity and heterogeneity in diagnosing and managing EPS, emphasising an unmet need for standardised therapeutic guidelines. Early diagnosis, tailored treatment strategies, and a multidisciplinary approach are crucial to improving patients’ outcomes.
Living donor kidney transplantation (LDKT) accounts for 35% of kidney transplants in the UK. The Organ Donation and Transplantation 2030 initiative underscores the necessity to enhance LDKT rates to meet growing demand. There is limited data on national variations in live donor workup pathways from initial referral to long-term follow-up. We conducted an online survey across all 23 UK transplant centres performing LDKT, covering the entire living donor pathway. We aimed to explore and highlight practice variation and identify opportunities for improvement. Responses were received from 21 centres (91.3%). Marked variation was identified in donor acceptance criteria, including age limits, body mass index thresholds, and donor evaluation timelines (6–36 weeks). Differences were also noted in multidisciplinary team processes, kidney laterality decisions, and perioperative enhanced recovery protocols. All centres used laparoscopic techniques, with hand-assisted transperitoneal nephrectomy being most common (57.1%). Donor nephrectomy and implantation were conducted sequentially in 15 (71.4%) of centres, and in parallel in six (28.6%). Variation was also seen in follow-up duration with 47.6% of centres offering lifelong follow-up. Despite excellent national outcomes, this survey highlights significant variation. Standardising key processes could streamline donor pathways, improve experiences, and support increased LDKT activity in the UK.
Abstract Purpose Practise variability exists in pancreas transplantation, but the extent across the EU is unknown. We surveyed pancreas transplant surgeons to assess current practices. Methods A 40-question survey was sent to 84 surgeons at 17 centres in 8 EU countries. Validity and reliability were analysed. Variability was evaluated using descriptive statistics and random effects modelling. Results The response rate was 92% (78/84). The survey demonstrated good validity and reliability (Cronbach’s alpha 0.82). Substantial variability existed in donor selection criteria such as acceptable BMI (range <10 to 35) and age (<30 to >60 years). Back-bench preparation also varied, including arterial reconstruction (52% continuous vs. 48% interrupted sutures) and duodenal closure (66% always buried staple line, 34% not). Systemic portal venous drainage was most common (70%), but 22% used portal drainage. Post-operative anticoagulation varied from 1 week to 3 months in duration. Random effects modelling found significant variability attributable to individual surgeons, centres, and case factors. Conclusions This rigorous survey identified modifiable targets to improve the quality and consistency of pancreas transplantation across the EU. Standardised best practise guidelines should focus on reducing variability in donor selection, back-bench preparation, surgical techniques, and post-operative management. Volume of Pancreas Transplants Performed Annually per CenterNumber of Transplants PerformedRespondents, n (%)<1036 (46%)11-2016 (21%)21-4013 (17%)41-608 (10%)605 (6%) Surgical Experience of RespondentsNumber of PancreasTransplants Performed AnnuallyRespondents, n (%)<24 (5%)2-528 (36%)6-817 (22%)8-129 (12%)1520 (26%)
BackgroundEncapsulating peritoneal sclerosis (EPS) is a rare complication of prolonged peritoneal dialysis (PD) exposure, characterised by peritoneal thickening, calcification, and fibrosis ultimately presenting with life-threatening bowel obstruction. The presence or role of peritoneal calcification in the pathogenesis of EPS is poorly characterised. We hypothesise that significantly aberrant bone mineral metabolism in patients on PD can cause peritoneal calcification which may trigger the development of EPS. We compared the temporal evolution of bone mineral markers during PD in EPS patients with non-EPS long-term PD controls.MethodsLinear mixed model and logistic regression analysis were used to compare four-monthly serum levels of calcium, phosphate, parathyroid hormone, and alkaline phosphatase (ALP) over the duration of PD exposure in 46 EPS and 46 controls (PD, non-EPS) patients.ResultsEPS patients had higher mean calcium (2.51 vs. 2.41 mmol/L) and ALP (248.00 vs. 111.13 IU/L) levels compared with controls (p=0.01 and p<0.001 respectively, maximum likelihood estimation). Logistic regression analysis demonstrated that high serum calcium and phosphate levels during PD were associated with a 4.5 and 2.9 fold increase in the risk of developing EPS respectively.ConclusionHigh levels of calcium and phosphate in patients on PD were identified to be risk factors for EPS development. Possible reasons for this may be an imbalance of pro-calcifying factors and calcification inhibitors promoting peritoneal calcification which increases peritoneal stiffness. Mechanical alterations may trigger, unregulated fibrosis and subsequent development of EPS. Improved management of secondary hyperparathyroidism during PD may ultimately diminish the EPS risk.
The oral microbiome is influenced by environmental factors in chronic kidney disease and following kidney transplantation affecting microbial composition, which may have implications for health and recovery. A major driver of oral microbiome perturbation is the accumulation of urea in saliva. We have modelled increased salivary urea concentrations associated with CKD and subsequent reductions that may occur post-transplantation. Oral microbiota were established in constant-depth film fermenters by inoculation with saliva. Duplicate validation runs were maintained with artificial saliva with baseline urea concentrations (0.205 mg/mL) for 21 days. Triplicate treatment runs were then done with baseline urea for 10 days (healthy phase) before urea was increased for 10 days to reflect CKD concentrations (0.92 mg/mL) (CKD phase). This was followed by reversion to baseline urea concentrations (post-transplant phase). Biofilms in primary validation runs reached dynamic stability within 5 days according to viable counting. DNA sequence data indicated minimal taxonomic variation over time and between low and high urea treatments despite background noise indicating changes in bacteria belonging to the family Gemellaceae and the genera TG5 and Leptotrichia. Significant differences in alpha and beta diversity occurred between low and high urea states but not following reversion to a low urea environment. Increased abundance of the TG5 was detected in late model phases, despite apparent count stability, and independent of changes in urea concentrations. IMPORTANCE:This study investigates dynamic changes in the oral microbiome associated with changes in salivary urea concentration, an important factor in chronic kidney disease (CKD). The in vitro system modeled increased urea concentrations and subsequent reductions post-transplantation. The study provides insight into the oral microbial shifts during different simulated clinical phases. Understanding these dynamics is crucial for advancing our comprehension of CKD-associated oral microbiome variations and their potential impact on patient well-being and recovery.
Organ donation continues to be low among ethnic minorities in the United Kingdom (UK), especially within the South Asian community, with a disproportionate number of patients of South Asian ethnicity awaiting organ transplants. In 2020/21, Minority Ethnic (ME) patients comprised almost a third of the national transplant waiting list, highlighting the continued imbalance between the need for transplants in South Asian communities and the availability of suitable organs. Median waiting times for transplants show that, generally, white patients wait less time than ME patients; Only 39.5% of ME families consented to proceed with deceased organ donation when approached compared to 69% of white families. How to increase awareness among the South Asian community on the scarcity of organ donors continues to be a growing challenge facing the healthcare system in the UK and globally. This article reflects on the education strategy implemented using the Health Belief Model. It provides a detailed framework with which to consider the rationale that led to a specific behaviour, in this case organ donation among the three major ethnicities (i.e., Indian, Pakistani, Bangladeshi) within the South Asian community as part of a single study.
OBJECTIVES:Pancreas transplant can have serious complications requiring salvage pancreatectomy, and surgical approaches should be carefully considered, with jejunal or ileal anastomoses most often employed. The jejunum may reduce gastrointestinal disturbance, whereas the ileum is more immunogenic. Proximal gastrointestinal anastomoses pose challenges with salvage pancreatectomy and creation of high-output stoma, often in the context of end-stage renal failure. Here, we compared outcomes between these techniques.MATERIALS AND METHODS:We retrospectively analyzed patient records of simultaneous pancreas and kidney transplants at a single center between 2013 and 2015, with follow-up to 2020.RESULTS:Our center performed 86 simultaneous pancreas and kidney transplants during the study period; 10 patients were excluded because of incomplete records of anastomosis type. Of included recipients, 59.2% were men (mean age 41.5 ± 8.4 y), 72.4% were donors after brain death, and 98.7% had received a first pancreas transplant. Forty-three simultaneous pancreas and kidney transplants were performed with ileal anastomosis and 33 with jejunal anastomosis. We found no significant differences in recipient or donor factors or immunosuppression regimen between anastomosis groups and no significant differences in overall patient, pancreas, or kidney graft survival or in gastrointestinal complications. Hospital length of stay was higher with ileal anastomosis (median 14 vs 19 days; P < .05), as was cold ischemic time (median 8:48 vs 9:31 hours; P < .05). Three patients required salvage pancre-atectomy and loop ileostomy formation with multiorgan support, prolonged intensive care unit stay, relaparotomy, and/or laparostomy.CONCLUSIONS:Long-term outcomes were comparable between our patient groups. Catastrophic complica-tions occur in a minority of cases, requiring salvage surgery. More complications occurred with ileal anastomosis, but this approach allows graft pancreatectomy and formation of loop ileostomy, avoiding a more proximal stoma in clinically unstable patients. Further studies are needed to examine the impact of enteric anastomosis site.
Introduction: Arteriovenous grafts (AVG) for haemodialysis (HD) access are recommended as a second line modality due to higher morbidity and mortality rates than arteriovenous fistulae (AVF). Smoking is already established as a risk factor in lower extremity bypass graft failure used for peripheral vascular disease, but its effect on AVGs remains unclear. We aimed to investigate the relationship of smoking on AVG outcomes. Methods: A 3 year (01/08/2015-01/08/2018) multi-centre retrospective study was carried out on patients receiving an AVG for HD. Data included patient demographics, medical history, operation, type of graft, postoperative course and primary and secondary patency rates. Statistical analyses performed were Kaplan-Meier curves and Cox's proportional hazard regression. Results: Fifty-five AVGs were performed (1052 AVF performed) in this period. The most common complication was thrombosis (38.9%). Primary patency at 6, 12 and 24 months were 55%, 45% and 44% respectively. Secondary patency at 6, 12 and 24 months were 63%, 56% and 54% respectively. Smoking was found to be a poor prognostic factor for primary (HR 3.734 (1.818-7.668 95% CI) p < 0.001) and secondary patency (HR 6.238 (2.729-14.257) p < 0.001). Smoking was also significantly associated with graft thrombosis (HR 5.741 (2.380-13.848 95% CI) p < 0.001). Discussion: Primary patency rates are lower than previous reports whilst secondary patency is equivalent. Smoking results in a greater risk of thrombosis and poorer primary and secondary patency. This is recognised in vascular surgical grafts, but has not been previously described in AVGs for HD access. Smoking is a modifiable risk factor and as AVGs are typically used for end-stage vascular access patients. Pre-operative strategies to promote smoking cessation, including patient education and prehabilitation should be employed to improve outcomes.