1,958 research outputs found
Successful Transplantation of Human Kidneys Deemed Untransplantable but Resuscitated by Ex Vivo Normothermic Machine Perfusion
We report the successful transplantation of a pair of human kidneys that were declined for transplantation due to inadequate in situ perfusion but subsequently transplanted after perfusion and assessment using ex vivo normothermic perfusion (EVNP). The kidneys were from a 35-year-old man, a donation after circulatory death donor. Both kidneys were declined by all UK transplant centers. On arrival, the kidneys had significant areas of incomplete clearance of blood from the microcirculation that did not clear after a further attempt to flush them. Kidneys underwent 60 min of EVNP with an oxygenated packed red blood cell–based solution warmed to 35.2°C. During EVNP, the patchy areas cleared in both kidneys. The mean renal blood flow and total urine output were 68.0 mL/min/100 g and 560 mL in the left kidney and 59.9 mL/min/100 g, 430 mL in the right, respectively. Based on the EVNP perfusion parameters, both kidneys were deemed suitable for transplantation. They were transplanted without any complications, and both recipients had initial graft function. The serum creatinine levels at 3 months were 1.2 mg/dl in the recipient of the left kidney and 1.62 mg/dl in the recipient of the right kidney. EVNP technology can be used to assess and rescue kidneys previously deemed unsuitable for transplantation.This study was supported by Kidney Research UK. The research was also funded by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, or NHSBT
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Normothermic machine perfusion for the assessment and transplantation of declined human kidneys from donation after circulatory death donors.
BACKGROUND: A significant proportion of donation after circulatory death (DCD) kidneys are declined for transplantation because of concerns over their quality. Ex vivo normothermic machine perfusion (NMP) provides a unique opportunity to assess the quality of a kidney and determine its suitability for transplantation. METHODS: In phase 1 of this study, declined human DCD kidneys underwent NMP assessment for 60 min. Kidneys were graded 1-5 using a quality assessment score (QAS) based on macroscopic perfusion, renal blood flow and urine output during NMP. In phase 2 of the study, declined DCD kidneys were assessed by NMP with an intention to transplant them. RESULTS: In phase 1, 18 of 42 DCD kidneys were declined owing to poor in situ perfusion. After NMP, 28 kidneys had a QAS of 1-3, and were considered suitable for transplantation. In phase 2, ten of 55 declined DCD kidneys underwent assessment by NMP. Eight kidneys had been declined because of poor in situ flushing in the donor and five of these were transplanted successfully. Four of the five kidneys had initial graft function. CONCLUSION: NMP technology can be used to increase the number of DCD kidney transplants by assessing their quality before transplantation
An Assessment of Urinary Biomarkers in a Series of Declined Human Kidneys Measured During ex-vivo Normothermic Kidney Perfusion
BACKGROUND: The measurement of urinary biomarkers during ex-vivo normothermic kidney perfusion (EVKP) may aid in the assessment of a kidney prior to transplantation. This study measured levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin-1 (ET-1) during EVKP in a series of discarded human kidneys. METHODS: Fifty six kidneys from deceased donors were recruited into the study. Each kidney underwent 60 minutes of EVKP and was scored based on the macroscopic appearance, renal blood flow and urine output. The scores ranged from 1 (least injury) to 5 (most severe). Levels of oxygen consumption, extraction, creatinine fall and fractional excretion of sodium were measured during perfusion. Urinary levels of NGAL, KIM-1 and ET-1 were measured after EVKP. RESULTS: Thirty eight kidneys had an EVKP score of 1 or 2, 8 a score of 3 and 10 a score of 4 or 5. During EVKP lower levels of oxygen consumption, higher oxygen extraction, a lower decrement of serum creatinine and higher levels of NGAL and ET-1 were associated with a higher EVKP score (P<0.05). These parameters were also associated with a raised creatinine level in the donor before organ retrieval. Levels of KIM-1 were not associated with the perfusion parameters (P=0.649) or renal function in the donor (R=0.02458: P=0.271). CONCLUSION: The measurement of urinary biomarkers, particularly NGAL in combination with functional perfusion parameters and the EVKP score provides an informative measure of kidney quality which may aid the decision to transplant the kidney.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.This study was supported by Kidney Research UK. The research was also funded by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT)
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Ex-vivo normothermic perfusion in renal transplantation: past, present and future
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Marginal donor kidneys make up a substantial proportion of transplanted kidneys. Nonetheless, they are more susceptible to injury during procurement and preservation. Normothermic perfusion is an alternative method of organ preservation that can be used to improve the quality, resuscitate, assess and potentially repair the organ. This review provides an up-to-date summary of the role of normothermic perfusion in renal transplantation and what we can expect in the future.
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Normothermic perfusion has been demonstrated to be a feasible and well tolerated method of organ preservation in a series of extended criteria donor kidneys. Furthermore, normothermic perfusion can be used as a quality assessment tool for kidneys pretransplant. In the future, normothermic perfusion could be used to manipulate the organ using gene and stem cell therapies ameliorating renal function after injury.
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In the last 5 years, normothermic perfusion has been translated from an experimental laboratory technique into clinical practice with promising results. Normothermic perfusion has demonstrated itself to be multifaceted in its application in renal transplantation. It may improve early graft function and can be used to assess the quality of the kidney before transplantation. The implications of these applications are crucial in maximizing the use of donor organs available in the perpetual climate of organ shortage
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Kidney perfusion: some like it hot others prefer to keep it cool.
Purpose of review: Machine perfusion technologies provide an opportunity for improved preservation, organ assessment, and resuscitation of damaged kidneys. This review summarizes the recent advances in hypothermic and normothermic kidney machine perfusion technologies.
Recent findings: Modifications to the perfusion conditions with the addition of oxygen during hypothermic machine perfusion can support a low level of metabolism, which in experimental settings improves graft function. Normothermic machine perfusion technologies are evolving in different directions including short-duration resuscitation, more prolonged periods of perfusion, and the transition between hypothermic and normothermic conditions. Clinical trials are ongoing in both hypothermic and normothermic settings. Functional parameters can be used to assess kidney quality and although normothermic machine perfusion may hold an advantage over hypothermic machine perfusion, new metabolomic, proteomic, and genomic technologies may be applied in the future to both technologies to provide more rigorous information on kidney quality. Promoting recovery by introducing an intervention during perfusion is an attractive area of research and therapies targeting the endothelium are a particular area of interest.
Summary: A great deal of research is still needed to optimize and logistically place hypothermic and normothermic perfusion technologies. In the future, we may progress toward organ-tailored preservation whereby high-risk kidneys can undergo assessment and repair before transplantation.The research was supported by the National Institute for Health Research Blood and Transplant Research Unit (NIHR BTRU) in Organ Donation and Transplantation at the University of Cambridge in collaboration with Newcastle University and in partnership with NHS Blood and Transplant (NHSBT)
Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation
Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment. However, how best to deliver these preservation methods or improve organ quality has not yet been conclusively defined. This review summarises the promising advances in machine perfusion science in recent years, which have the potential to further improve early graft function and prolong graft survival.</jats:p
Response to "Past, Present, and Future of Dynamic Kidney and Liver Preservation and Resuscitation"
We are writing in response to the article written by Jochmans et al [1]. The article is a comprehensive review on the status of preservation and resuscitation techniques in kidney and liver transplantation. It highlights the need for dynamic techniques of preservation for higher-risk kidney and liver grafts, detailing hypothermic and normothermic perfusion technologies. The review also documents a list of registered clinical trials of these novel techniques in kidney transplantation. The supporting information (S1) also lists the planned or ongoing trials that are unregistered. The authors state that, currently, there are no registered ongoing clinical trials comparing preimplantation normothermic machine perfusion with static cold storage
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Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine.
BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of small intestine, 1.5-3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer's solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5-3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. RESULTS: After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. CONCLUSIONS: This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions
Protocol of a randomised controlled, open-label trial of ex vivo normothermic perfusion versus static cold storage in donation after circulatory death renal transplantation.
Introduction: Ex vivo normothermic perfusion (EVNP) is a novel technique that reconditions the kidney and restores renal function prior to transplantation. Phase I data from a series of EVNP in extended criteria donor kidneys have established the safety and feasibility of the technique in clinical practice.
Methods and analysis: This is a UK-based phase II multicentre randomised controlled trial to assess the efficacy of EVNP compared with the conventional static cold storage technique in donation after circulatory death (DCD) kidney transplantation. 400 patients receiving a kidney from a DCD donor (categories III and IV, controlled) will be recruited into the study. On arrival at the transplant centre, kidneys will be randomised to receive either EVNP (n=200) or remain in static cold storage (n=200). Kidneys undergoing EVNP will be perfused with an oxygenated packed red cell solution at near body temperature for 60 min prior to transplantation. The primary outcome measure will be determined by rates of delayed graft function (DGF) defined as the need for dialysis in the first week post-transplant. Secondary outcome measures include incidences of primary non-function, the duration of DGF, functional DGF defined as <10% fall in serum creatinine for 3 consecutive days in the first week post-transplant, creatinine reduction ratio days 2 and 5, length of hospital stay, rates of biopsy-proven acute rejection, serum creatinine and estimated glomerular filtration rate at 1, 3, 6 and 12 months post-transplant and patient and allograft survival. The EVNP assessment score will be recorded and the level of fibrosis and inflammation will also be measured using tissue, blood and urine samples. Ethics and dissemination. The study has been approved by the National Health Service (NHS) Health Research Authority Research Ethics Committee. The results are expected to be published in 2020.
Trial registration number: ISRCTN15821205; Pre-results.Kidney Research UK (SP/MEKC/1/2014); University of Cambridge and University Hospitals of Cambridge Foundation Trust, Cambridge CB2 OQQ
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