Kidney Transplantation From Donors With Acute Kidney Injury: Are the Concerns Justified? A Systematic Review and Meta-Analysis.

Renal transplantation improves quality of life and prolongs survival in patients with end-stage kidney disease, although challenges exist due to the paucity of suitable donor organs. This has been addressed by expanding the donor pool to include AKI kidneys. We aimed to establish whether transplanting such kidneys had a detrimental effect on graft outcome. The primary aim was to define early outcomes: delayed graft function (DGF) and primary non-function (PNF). The secondary aims were to define the relationship to acute rejection, allograft survival, eGFR and length of hospital stay (LOS). A systematic literature review and meta-analysis was conducted on the studies reporting the above outcomes from PubMed, Embase, and Cochrane Library databases. This analysis included 30 studies. There is a higher risk of DGF in the AKI group (OR = 2.20, p < 0.00001). There is no difference in the risk for PNF (OR 0.99, p = 0.98), acute rejection (OR 1.29, p = 0.08), eGFR decline (p = 0.05) and prolonged LOS (p = 0.11). The odds of allograft survival are similar (OR 0.95, p = 0.54). Transplanting kidneys from donors with AKI can lead to satisfactory outcomes. This is an underutilised resource which can address organ demand.

Kidney Transplantation From Hepatitis-C Viraemic Donors:Considerations for Practice in the United Kingdom.

Background: Donor hepatitis-C (HCV) infection has historically represented a barrier to kidney transplantation (KT). However, direct-acting antiviral (DAA) medications have revolutionised treatment of chronic HCV infection. Recent American studies have demonstrated that DAA regimes can be used safely peri-operatively in KT to mitigate HCV transmission risk. Methods: To formulate this narrative review, a comprehensive literature search was performed to analyse results of existing clinical trials examining KT from HCV-positive donors to HCV-negative recipients with peri-operative DAA regimes. Results: 13 studies were reviewed (11 single centre, four retrospective). Outcomes for 315 recipients were available across these studies. A sustained virological response at 12 weeks (SVR12) of 100% was achieved in 11 studies. One study employed an ultra-short DAA regime and achieved an SVR12 of 98%, while another achieved SVR12 of 96% due to treatment of a missed mixed genotype. Conclusion: HCV+ KT is safe and may allow increased utilisation of organs for transplantation from HCV+ donors, who often have other favourable characteristics for successful donation. Findings from US clinical trials can be applied to the United Kingdom transplant framework to improve organ utilisation as suggested by the NHSBT vision strategy "Organ Donation and Transplantation 2030: meeting the need".

First World Consensus Conference on pancreas transplantation: Part II - recommendations.

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Links between a biomarker profile, cold ischaemic time and clinical outcome following simultaneous pancreas and kidney transplantation.

In sepsis, trauma and major surgery, where an explicit physiological insult leads to a significant systemic inflammatory response, the acute evolution of biomarkers have been delineated. In these settings, Interleukin (IL) -6 and TNF-α are often the first pro-inflammatory markers to rise, stimulating production of acute phase proteins followed by peaks in anti-inflammatory markers. Patients undergoing SPKT as a result of diabetic complications already have an inflammatory phenotype as a result of uraemia and glycaemia. How this inflammatory response is affected further by the trauma of major transplant surgery and how this may impact on graft survival is unknown, despite the recognised pro-inflammatory cytokines' detrimental effects on islet cell function. The aim of the study was to determine the evolution of biomarkers in omentum and serum in the peri-operative period following SPKT. The biochemical findings were correlated to clinical outcomes. Two omental biopsies were taken (at the beginning and end of surgery) and measured for CD68+ and CD206+ antibodies (M1 and M2 macrophages respectively). Serum was measured within the first 72 h post-SPKT for pro- and anti-inflammatory cytokines (IL -6, -10 and TNF-α), inflammatory markers (WCC and CRP) and endocrine markers (insulin, C-peptide, glucagon and resistin). 46 patients were recruited to the study. Levels of M1 (CD68+) and M2 (CD206+) macrophages were significantly raised at the end of surgery compared to the beginning (p = 0.003 and p < 0.001 respectively). Levels of C-peptide, insulin and glucagon were significantly raised 30 min post pancreas perfusion compared to baseline and were also significantly negatively related to prolonged cold ischaemic time (CIT) (p < 0.05). CRP levels correlated significantly with the Post-Operative Morbidity Survey (p < 0.05). The temporal inflammatory marker signature after SPKT is comparable to the pattern observed following other physiological insults. Unique to this study, we find that CIT is significantly related to early pancreatic endocrine function. In addition, this study suggests a predictive value of CRP in peri-operative morbidity following SPKT.

Unlocking the post-transplant microenvironment for successful islet function and survival.

Islet transplantation (IT) offers the potential to restore euglycemia for patients with type 1 diabetes mellitus (T1DM). Despite improvements in islet isolation techniques and immunosuppressive regimes, outcomes remain suboptimal with UK five-year graft survivals (5YGS) of 55% and most patients still requiring exogenous insulin after multiple islet infusions. Native islets have a significant non-endocrine component with dense extra-cellular matrix (ECM), important for islet development, cell survival and function. Collagenase isolation necessarily disrupts this complex islet microenvironment, leaving islets devoid of a supporting framework and increasing vulnerability of transplanted islets. Following portal venous transplantation, a liver injury response is potentially induced, which typically results in inflammation and ECM deposition from liver specific myofibroblasts. The impact of this response may have important impact on islet survival and function. A fibroblast response and ECM deposition at the kidney capsule and eye chamber alongside other implantation sites have been shown to be beneficial for survival and function. Investigating the implantation site microenvironment and the interactions of transplanted islets with ECM proteins may reveal therapeutic interventions to improve IT and stem-cell derived beta-cell therapy.

Jejunal or Ileal Exocrine Drainage in Pancreas Transplantation: Impact on Gastrointestinal Function.

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.