Bariatric surgery improves access to renal transplantation and is safe in renal failure as well as after transplantation: A systematic review and meta-analysis.

INTRODUCTION: Effective workup and listing of end-stage renal disease (ESRD) patients for renal transplantation, often with multiple co-morbidities, poses a challenge for transplant teams. Obesity is a common co-morbidity associated with adverse outcomes in ESRD and kidney transplant (KT) recipients. Bariatric and metabolic surgery (BMS) has long been established as a safe and effective treatment for morbid obesity. In this study, the authors aimed to evaluate the strength of evidence for both the efficacy and safety of bariatric surgery in patients with ESRD or kidney transplantation. METHODS: A literature search was performed using key terms including "transplantation", "kidney", "renal", "obesity", and "bariatric". Databases searched include MEDLINE, EMBASE and Web of Science from inception to date (April 2021). Methodological quality was assessed using the Newcastle-Ottawa tool. Selected articles were then categorised into patients awaiting waiting list acceptance, patients awaiting transplantation, patients undergoing simultaneous BMS + KT and patients undergoing BMS following a previous renal transplant. Summary effects are presented with a level of statistical significance and 95% Confidence Intervals. RESULTS: A total of 28 articles were selected following the literature search. Fourteen studies on patients awaiting listing (n = 1903), nine on patients on the KT waiting list (n = 196), a single study on simultaneous BMS and KT and ten studies on patients undergoing BMS following KT (n = 198). Mean change in BMI for patients awaiting listing was -11.3 kg/m2 (95%CI: -15.3 to -7.3, p < 0.001), mean change in BMI for patients listed for KT was -11.2 kg/m 2(95%CI: -12.9 to -9.5, p 0.001) and mean change for patients with prior KT was -11.0 kg/m2 (95%CI: -7.09 to -14.9, p < 0.001). The combined mortality rate for patients who had undergone both BMS and KT was 4% (n = 15). DISCUSSION: This review demonstrates BMS is both safe and efficacious in patients with ESRD prior to KT and in those post KT. It would enable difficult-to-list obese recipients the possibility to undergo transplantation and should be considered as part of the work up process.

Assessment of Mitochondrial Function and Oxygen Consumption Measured During Ex Vivo Normothermic Machine Perfusion of Injured Pig Kidneys Helps to Monitor Organ Viability.

Donor kidney assessment may improve organ utilisation. Normothermic Machine Perfusion (NMP) has the potential to facilitate this advance. The mechanism of action is not yet determined and we aimed to assess mitochondrial function during NMP. Anaesthetised pigs (n = 6) had one kidney clamped for 60 min. The healthy contralateral kidney was removed and underwent NMP for 8 h (healthy control (HC), n = 6). Following 60 min warm ischaemia the injured kidney underwent HMP for 24 h, followed by NMP for 8 h (n = 6). Mitochondria were extracted from fresh tissue for analysis. Injured kidneys were analysed as two separate groups (IMa, n = 3 and IMb, n = 3). Renal resistance was higher (0.39ï, ± 0.29 vs. 1.65ï, ± 0.85; p = 0.01) and flow was lower (55ï, ± 28 vs. 7ï, ± 4; p = 0.03) during HMP in IMb than IMa. NMP blood flow was higher in IMa versus IMb (2-way ANOVA; p < 0.001) After 60 min NMP, O2 consumption was significantly lower in IMb versus IMa (p ≤ 0.002). State-3 respiration was significantly different between the groups (37ï, ± 19 vs. 24ï, ± 14 vs. 10ï, ± 8; nmolO2/min/mg; p = 0.049). Lactate levels were significantly lower in IMa versus IMb (p = 0.028). Mitochondrial respiration levels during NMP may be suggestive of kidney viability. Oxygen consumption, renal blood flow and lactate can differentiate severity of kidney injury during NMP.

Abdominal multiorgan procurement from slaughterhouse pigs: a bespoke model in organ donation after circulatory death for ex vivo organ perfusion compliant with the 3 Rs (Reduction, Replacement & Refinement).

BACKGROUND: Advances in organ preservation, reconditioning and assessment have been driven by the increasing necessity to utilise organs from extended criteria donors, particularly donors after circulatory death. Research efforts in this area have aided translation of machine perfusion technology into clinical practice. Pigs are anatomically and physiologically similar to humans and are an excellent model. However, conducting large animal experimental research is challenging and typically limited by ethical and economic constraints. Here we describe a reproducible, cost-effective multi-organ abdominal procurement model of porcine organs from the slaughterhouse. METHODS: Domestic pigs are electrically stunned and exsanguinated following the standard abattoir process. Via a longitudinal midline incision, the thoracoabdominal viscera are removed en bloc by incising along the anterior vertebral plane. The abdominal organs are isolated, perfused and separated preserving their respective vasculature, allowing individual organ use for specific experiments. RESULTS: The warm ischaemic time is kept between 15-30 minutes. Using this highly protocolized procurement technique we have procured 12 livers, 162 kidneys and 12 pancreata for research, the majority of which have been utilized for ex situ perfusion experiments. CONCLUSIONS: We have described a reliable and reproducible procedure for abdominal multi-organ procurement from slaughterhouse pigs.

Development of ex situ normothermic reperfusion as an innovative method to assess pancreases after preservation.

Static cold storage (SCS) is the standard method for pancreas preservation prior to transplantation; however, it does not permit organ assessment. Normothermic reperfusion (NR) is utilized clinically for other organs to assess viability. Our aim was to develop NR using normothermic machine perfusion technique to simulate reperfusion at the time of transplantation, enabling evaluation of oxygenated hypothermic machine perfusion (HMPO2) as a newer strategy to optimize pancreas preservation. 13 porcine pancreases procured after circulatory death were divided into 3 groups: 4 pancreases preserved using SCS, and 2 groups preserved by HMPO2 (n = 4 and n = 5, differing by type of preservation solution). Duration of perfusion or cold storage was 6 hours before the 1-hour assessment using NR. Outcome measures were perfusion characteristics, biochemistry and change in tissue water mass as oedema assessment. During NR, the HMPO2 groups demonstrated better perfusion characteristics, normal macroscopic appearances, decreased water mass and one HMPO2 group demonstrated a response to glucose stimulation. Conversely, the SCS group showed an increased water mass and developed early macroscopic appearances of oedema, interstitial haemorrhage and minimal portal outflow. This study suggests that ex situ assessment of pancreases by NR is promising, and that HMPO2 may be better than SCS.

Ischemia-Reperfusion Injuries Assessment during Pancreas Preservation.

Maintaining organ viability between donation and transplantation is of critical importance for optimal graft function and survival. To date in pancreas transplantation, static cold storage (SCS) is the most widely practiced method of organ preservation. The first experiments in ex vivo perfusion of the pancreas were performed at the beginning of the 20th century. These perfusions led to organ oedema, hemorrhage, and venous congestion after revascularization. Despite these early hurdles, a number of factors now favor the use of perfusion during preservation: the encouraging results of HMP in kidney transplantation, the development of new perfusion solutions, and the development of organ perfusion machines for the lung, heart, kidneys and liver. This has led to a resurgence of research in machine perfusion for whole organ pancreas preservation. This review highlights the ischemia-reperfusion injuries assessment during ex vivo pancreas perfusion, both for assessment in pre-clinical experimental models as well for future use in the clinic. We evaluated perfusion dynamics, oedema assessment, especially by impedance analysis and MRI, whole organ oxygen consumption, tissue oxygen tension, metabolite concentrations in tissue and perfusate, mitochondrial respiration, cell death, especially by histology, total cell free DNA, caspase activation, and exocrine and endocrine assessment.

Comparison of the outcomes of the pediatric kidney transplantation between recipients below and above 15 kg: a single center retrospective study.

BACKGROUND: The renal transplantation is the best treatment for end-stage renal disease in children. We present the findings of an analysis of our institution's paediatric transplant outcomes comparing recipients under 15 kg, who represent this potentially higher risk group, to those above 15 kg. METHODS: We retrospectively identified consecutive paediatric kidney transplants from a prospectively collected database for analysis. We included all recipients under the age of 18 years at the time of transplant between 2006 and 2018 without any exclusion criteria. The primary outcome was death-censored graft survival at 1 year, 5 years and 10 years. RESULTS: 109 paediatric kidney transplants were performed in 100 children. Graft survival in the all population was 98%, 96% and 76% at 1 year, 5 years and 10 years, respectively. Recipient weight below 15 kg was not found to be a risk factor of graft loss. Overall, we found no individual factor to be statistically significantly associated with renal graft lost. The overall complication rate was 16% (18/109) with 12 early complications (11%) and 6 late ones (5%). CONCLUSION: Kidney transplantation in children weighing < 15 kg seems safe and offers the same patient and graft survival outcomes as in other (> 15 kg) pediatric recipients with equally low complication rates.

The novel use of the Haemodialysis reliable outflow graft (HeRo®) in intestinal failure patients with end-stage vascular access.

Intestinal failure (IF) patients are dependent on central venous access to receive parenteral nutrition. Longstanding central venous catheters are associated with life-threatening complications including infections and thromboses resulting in multiple line exchanges and the development ofprogressive central venous stenosis or occlusion. The Haemodialysis Reliable Outflow (HeRO) graft is an arterio-venous device that has been successfully used in haemodialysis patients with 'end-stage vascular access'. We describe a case series of HeRO graft use in patients with IF and end-stage vascular access. Four HeRO grafts were inserted into IF patients with end-stage vascular access to facilitate or support intestinal transplantation. In all patients the HeRO facilitated immediate vascular access, supporting different combinations of parenteral nutrition, intravenous medications, fluids or renal replacement therapy with no bloodstream infections. In a highly complex group of IF patients with central venous stenosis/occlusion limiting conventional venous access or at risk of life-threatening catheter-related complications, a HeRO® graft can be a feasible alternative.

Normothermic Machine Perfusion (NMP) of the Liver as a Platform for Therapeutic Interventions during Ex-Vivo Liver Preservation: A Review.

Liver transplantation is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. This has necessitated the adoption of innovative technologies and strategies to protect these higher-risk grafts from the deleterious effects of traditional preservation and ischaemia reperfusion injury (IRI). The advent of normothermic machine perfusion (NMP) and rapid growth in the clinical adoption of this technology has accelerated efforts to utilise NMP as a platform for therapeutic intervention to optimise donor livers. In this review we will explore the emerging preclinical data related to ameliorating the effects of IRI, protecting the microcirculation and reducing the immunogenicity of donor organs during NMP. Exploiting the window of opportunity afforded by NMP, whereby the liver can be continuously supported and functionally assessed while therapies are directly delivered during the preservation period, has clear logistical and theoretical advantages over current preservation methods. The clinical translation of many of the therapeutic agents and strategies we will describe is becoming more feasible with widespread adaptation of NMP devices and rapid advances in molecular biology and gene therapy, which have substantially improved the performance of these agents. The delivery of novel therapeutics during NMP represents one of the new frontiers in transplantation research and offers real potential for successfully tackling fundamental challenges in transplantation such as IRI.

Next-generation sequencing methods to detect donor-derived cell-free DNA after transplantation.

Following the initial technical challenge of implanting an organ, maintaining the organ against a vast array of pathologies for years to come, remains a colossal challenge for all clinicians working in transplantation. Drug toxicity, opportunistic infection, primary disease recurrence, and the constant battle against organ rejection are all differentials that are considered when graft dysfunction is observed, promoting a lifetime of laborious surveillance. Cell free DNA (cfDNA) since its discovery in 1948 has made an impactful change in transplantation. A growing body of evidence in transplantation (109 manuscripts from 55 studies) shows the promise of this tool as an early and accurate detection of allograft injury rejection as well the benefit to rule out injury as part of screening and routine monitoring. With next generation sequencing rapidly becoming the standard of care in quantifying DNA, understanding this science in the context of transplantation is critical to ensure studies, outcomes and care is improved.

Bilateral Nephrectomy for Autosomal Dominant Polycystic Kidney Disease and Timing of Kidney Transplant: A Review of the Technical Advances in Surgical Management of Autosomal Dominant Polycystic Disease.

Autosomal dominant polycystic disease is a multisystem inherited condition affecting the kidneys and is an important cause of end-stage renal disease. Patients with autosomal dominant polycystic disease experience symptoms related to size and cystic nature of their kidneys, which can be difficult to manage. Traditionally, the only surgical option for management was open bilateral/unilateral native nephrectomy, which carried with it significant morbidity and mortality. Therefore, it was deemed unsafe and rarely performed. However, surgery for autosomal dominant polycystic disease has evolved rapidly with the advent of minimally invasive surgery and improved medical management of end-stage renal failure patients. Laparoscopic and hand-assisted laparoscopic techniques have been adopted and have demonstrated reduced morbidity. The timing of this intervention in relation to transplant is controversial and presents a major challenge in managing this patient population.

Preoperative quality of life in patients with degenerative spinal disorders: many are worse than patients with brain tumours and cancer.

BACKGROUND: This study compared prospectively the quality of life (QoL), function and mood of patients about to undergo surgery for either an intracranial supratentorial tumour or a spinal degenerative condition. The QoL scores were also compared to that of cohorts with a range of extracranial cancers. MATERIAL AND METHODS: The study took place in a Scottish NHS Neurosurgical Unit. Patients were assessed on the day prior to surgery for their QoL (European Organisation for Research and Treatment of Cancer (EORTC)-QLQ C30), mood status (Hospital Anxiety and Depression Score), Performance status (Karnosky Score, timed 10-m walk) and disability (Barthel Disability Index). All tests were performed by a single trained psychologist. RESULTS: Between 2007 and 2009, 101 patients with intracranial tumours, 75 age- and gender-matched patients with degenerative spinal disorders and 80 healthy adults were evaluated. There was no difference in the mood or disability scores between the two patient cohorts, but mood was significantly worse than a matched healthy cohort. The spinal cohort had significantly worse scores on the Karnovsky Scale, timed 10-m walk and for Global Health than those of the brain tumour cohort. They also had worse mean scores on all five functional scales, as well as six of the nine symptom/single-item scales, of the EORTC QLQ C30. SUMMARY: Patients with degenerative spinal disorders awaiting surgery on the NHS have significantly impaired QoL in multiple domains as well as other functional and mood disorders. Not only are their scores worse than a brain tumour cohort but they are also worse than many cancer cohorts described in the literature using the EORTC QLQ C30. These findings suggest that preoperative care, assessment and management of NHS patients with degenerative spinal disorders could be improved and that the EORTC QLQ C30 may be a useful tool for audit purposes in this cohort.