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      A Pilot Study of Postoperative Animal Welfare as a Guidance Tool in the Development of a Kidney Autotransplantation Model With Extended Warm Ischemia

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          Background.

          This pilot study aimed to maintain acceptable animal welfare in the development of a porcine autotransplantation model with severe and incremental renal ischemic injury, a model for usage in future intervention studies. Secondary aims were to develop and test methods to collect blood and urine without the need to restrain or use sedative and avoid transportation to optimize welfare of the pig.

          Methods.

          Kidneys from 7 female pigs were subjected to incremental durations of warm ischemia (WI) 30, 45, or 75 minutes by left renal artery and vein clamping. After static cold storage, contralateral nephrectomy was performed, and the injured graft was autotransplanted and animals observed for 14 days. Animal welfare was assessed and recorded using a structured scoring sheet before and 4 days after the kidney autotransplantation. Furthermore, blood samples were drawn daily the first week and every second day the following week using a semi-central venous catheter. An ostomy bag around the genitals was tested for urine collection. Measured glomerular filtration rate was calculated using renal clearance of chromium-51-labeled ethylenediamine tetraacetic acid on day 14.

          Results.

          None of the 7 animals died during the follow-up. The animal welfare was moderately affected when applying 75 minutes of WI (n = 2), and for that reason WI was not further increased. Pigs with lower WI had no observed welfare issues. With 75 minutes of WI peak, plasma creatinine was 1486 and 1317 µmol/L, reached on day 4. Lowest glomerular filtration rate levels were observed in the pigs with 75 minutes of WI.

          Conclusions.

          WI up to 75 minutes caused the intended severely impaired renal function without significantly compromising animal welfare. Blood and urine was collected postoperatively without sedation of the pigs or use of a metabolic cage.

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          Most cited references 48

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          Delayed graft function in the kidney transplant.

          Acute kidney injury occurs with kidney transplantation and too frequently progresses to the clinical diagnosis of delayed graft function (DGF). Poor kidney function in the first week of graft life is detrimental to the longevity of the allograft. Challenges to understand the root cause of DGF include several pathologic contributors derived from the donor (ischemic injury, inflammatory signaling) and recipient (reperfusion injury, the innate immune response and the adaptive immune response). Progressive demand for renal allografts has generated new organ categories that continue to carry high risk for DGF for deceased donor organ transplantation. New therapies seek to subdue the inflammatory response in organs with high likelihood to benefit from intervention. Future success in suppressing the development of DGF will require a concerted effort to anticipate and treat tissue injury throughout the arc of the transplantation process. ©2011 The Authors Journal compilation © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.
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            Catheter-associated urinary tract infections.

             John Warren (2001)
            Nosocomial urinary tract infection (UTI) is the most common infection acquired in both hospitals and nursing homes and is usually associated with catheterization. This infection would be even more common but for the use of the closed catheter system. Most modifications have not improved on the closed catheter itself. Even with meticulous care, this system will not prevent bacteriuria. After bacteriuria develops, the ability to limit its complications is minimal. Once a catheter is put in place, the clinician must keep two concepts in mind: keep the catheter system closed in order to postpone the onset of bacteriuria, and remove the catheter as soon as possible. If the catheter can be removed before bacteriuria develops, postponement becomes prevention.
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              Effect of donor age and cold storage time on outcome in recipients of kidneys donated after circulatory death in the UK: a cohort study.

              Use of kidneys donated after controlled circulatory death has increased the number of transplants undertaken in the UK but there remains reluctance to use kidneys from older circulatory-death donors and concern that kidneys from circulatory-death donors are particularly susceptible to cold ischaemic injury. We aimed to compare the effect of donor age and cold ischaemic time on transplant outcome in kidneys donated after circulatory death versus brain death.
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                Author and article information

                Journal
                Transplant Direct
                Transplant Direct
                TXD
                Transplantation Direct
                Wolters Kluwer Health
                2373-8731
                November 2019
                08 October 2019
                : 5
                : 11
                Affiliations
                [1 ] Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
                [2 ] Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark.
                [3 ] Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
                [4 ] Department of Urology, Aarhus University Hospital, Aarhus, Denmark.
                [5 ] Nuffield Department of Surgical Sciences, Oxford Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
                [6 ] Department of Surgery, Organ Donation and Transplantation, University of Medical Center Groningen, Groningen, the Netherlands.
                [7 ] Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.
                Author notes
                Correspondence: Stine Lohmann, Department of Clinical Medicine, Aarhus University, Palle Juul-Jensens Blvd 99, 8200 Aarhus N, Denmark. ( stiloh@ 123456clin.au.dk ).
                Article
                00003
                10.1097/TXD.0000000000000941
                6831118
                Copyright © 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.

                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.

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                Kidney Transplantation
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