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Gelpi R, Paredes D, Rodríguez-Villar C, Roque R, Ruiz A, Adalia R, Peri-Cusí L, Sole M, Oppenheimer F, Diekmann F. The development of a predictive model of graft function in uncontrolled donors after circulatory death: validity of a pulsatile renal preservation machine cut-off value for kidney acceptance. Nephrol Dial Transplant 2019; 34:531-538. [PMID: 30085267 DOI: 10.1093/ndt/gfy241] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2017] [Accepted: 06/14/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND The criteria for kidney suitability in uncontrolled donors after circulatory death (uDCD) procured after regional normothermic perfusion are based on macroscopic appearance and renal haemodynamic values with final renal resistance (FRR). However, these criteria have not been analysed to predict the future graft function. This study presents a model to predict the outcome in uDCD kidneys and define the predictive FRR value. METHODS All uDCD kidney transplants performed in our hospital from 2004 to 2016 were included. Donors and recipients and pre-transplantation data are described. The endpoint was glomerular filtration rate (GFR) ≥30 mL/min at 6 months after transplantation. RESULTS A total of 194 recipients were included. FRR in donors ≥60 years old was (mean ± SD) 0.27 ± 0.11 versus 0.22 ± 0.09 mmHg/mL/min in donors <60 years (P = 0.042). Kidney survival was 88.2% versus 84% at 12 months and 60.7% versus 30.8% at 120 months (P = 0.067). For the group of recipients from donors ≥60 years, the FRR was 0.37 ± 0.08 mmHg/mL/min in the GFR <30 mL/min group versus 0.18 ± 0.06 mmHg/mL/min in the GFR ≥30 mL/min group (P < 0.001). The value FRR ≥0.3 mmHg/mL/min predicts 59-79% of GFR <30 mL/min [odds ratio = 2.16, 95% confidence interval (CI) 1.80-6.40; P < 0.001]. The predictive accuracy of FRR for GFR by ROC curve was 0.968 (95% CI). The best cut-off for FRR was 0.3 mmHg/mL/min to predict GFR at 6 months with a sensitivity of 67%, specificity of 100%, positive predictive value of 83% and negative predictive value of 92%. CONCLUSIONS Our results suggest that in uDCD donors the combination of donor age ≥60 years together with FRR ≥0.3 mmHg/mL/min could predict poor outcome at 6 months after transplantation in low immunological risk recipients.
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Affiliation(s)
- Rosana Gelpi
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - David Paredes
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Camino Rodríguez-Villar
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Rebeca Roque
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Angel Ruiz
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Ramon Adalia
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Luis Peri-Cusí
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Manel Sole
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Federico Oppenheimer
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
| | - Fritz Diekmann
- Nephrology and Renal Transplant Department, Donation and Transplant Coordination Department, Hospital Clínic i Universitari de Barcelona, Barcelona, Spain
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Singh S, Kumar S, Dasgupta S, Kenwar DB, Rathi M, Sharma A, Kohli HS, Jha V, Gupta KL, Minz M. A Single-center Experience of Kidney Transplantation from Donation after Circulatory Death: Challenges and Scope in India. Indian J Nephrol 2017; 27:205-209. [PMID: 28553041 PMCID: PMC5434687 DOI: 10.4103/0971-4065.202843] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Donation after circulatory death (DCD) has never been attempted in India because of legal constraints and lack of guidelines for the withdrawal of life support in end-of-life situations. The present report describes the initial experience of transplantation of organs from DCD donors in a tertiary care center in India. Between 2011 and 2015, five donors had kidneys retrieved after cardiac arrest. These patients were declared dead after waiting for 5 min with no electrocardiographic signal on monitor following cardiopulmonary resuscitation (CPR), which was restarted in three patients till organ retrieval. All donors received heparin and underwent rapid cannulation of aorta, infusion of preservative cold solution, and immediate surface cooling of organs during retrieval surgery. 9/10 kidneys were utilized. Mean donor age was 29.6 ± 16.3 years, M:F 4:1 and mean age of recipients was 38.7 ± 10.8 years, M:F 7:2. Seven patients required dialysis in postoperative period. Mean postoperative day 0 urine output was 1.9 ± 2.6 L. Baseline creatinine achieved was 1.38 ± 0.35 mg/dl after a mean duration of 26.12 ± 15.4 days. Kidneys from donors where CPR was continued after the declaration of death (n = 3) had better recovery of renal function (time to reach baseline creatinine 21.2 ± 7.2 vs. 34.3 ± 23.7 days, baseline creatinine 1.36 ± 0.25 vs. 1.52 ± 0.45 mg%). In donors without CPR, one kidney never functioned and others had patchy cortical necrosis on protocol biopsy, which was not seen in the kidneys from donors with CPR. Kidneys from DCD donors can serve as a useful adjunct in deceased donor program. Continuing CPR after the declaration of death seems to help in improving outcomes.
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Affiliation(s)
- S Singh
- Department of Renal Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - S Kumar
- Department of Renal Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - S Dasgupta
- Department of Renal Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - D B Kenwar
- Department of Renal Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - M Rathi
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - A Sharma
- Department of Renal Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - H S Kohli
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - V Jha
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - K L Gupta
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - M Minz
- Department of Renal Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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3
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Perera MTP, Bramhall SR. Current status and recent advances of liver transplantation from donation after cardiac death. World J Gastrointest Surg 2011; 3:167-76. [PMID: 22180833 PMCID: PMC3240676 DOI: 10.4240/wjgs.v3.i11.167] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2011] [Revised: 10/21/2011] [Accepted: 10/28/2011] [Indexed: 02/06/2023] Open
Abstract
The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a significant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably “prematurely” offered without ideal donor management or even prior to brain death being established. The absolute benefits of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.
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Affiliation(s)
- M Thamara Pr Perera
- M Thamara PR Perera, Simon R Bramhall, The Liver Unit, Queen Elizabeth Hospital, Edgbaston, Birmingham B15 2TH, United Kingdom
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4
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Henry SD, Guarrera JV. Protective effects of hypothermic ex vivo perfusion on ischemia/reperfusion injury and transplant outcomes. Transplant Rev (Orlando) 2011; 26:163-75. [PMID: 22074785 DOI: 10.1016/j.trre.2011.09.001] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2011] [Revised: 07/08/2011] [Accepted: 09/02/2011] [Indexed: 12/14/2022]
Abstract
Hypothermic machine preservation (HMP) has been used in renal transplantation since the late 1960s with recent robust prospective, multicenter data showing lower rates of delayed graft function and improved graft survival. Although now clearly beneficial for renal transplantation, extrarenal machine perfusion has remained predominantly in preclinical investigations. Pancreatic HMP has drawn little clinical interest because HMP has been suggested to cause graft edema and congestion, which is associated with early venous thrombosis and graft failure. Early investigation showed no benefit of HMP in whole-organ pancreas transplant. One report did show that HMP increases islet cell yield after isolation. Preclinical work in liver HMP has been promising. Short- and long-term HMP has been shown to improve graft viability and reduce preservation injury, even in animal models of steatotic and donation after cardiac death. The first clinical study of liver HMP using a centrifugal dual perfusion technique showed excellent results with lower hepatocellular injury markers and no adverse perfusion-related outcomes. In addition, a dramatic attenuation of proinflammatory cytokine expression was observed. Further studies of liver HMP are planned with focus on developing a reproducible and standard protocol that will allow the widespread availability of this technology. Future research and clinical trials of novel organ preservation techniques, solutions, and interventions are likely to bring about developments that will allow further reduction of preservation-related ischemia/reperfusion injury and improved outcomes and allow safer utilization of the precious and limited resource of donor organs.
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Affiliation(s)
- Scot D Henry
- Division of Abdominal Organ Transplantation and Molecular Therapies and Organ Preservation Research Laboratory, Department of Surgery Columbia University Medical Center, New York, NY 10032-3784, USA
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Doorschodt BM, Schreinemachers MCJM, Behbahani M, Florquin S, Weis J, Staat M, Tolba RH. Hypothermic machine perfusion of kidney grafts: which pressure is preferred? Ann Biomed Eng 2010; 39:1051-9. [PMID: 21161683 DOI: 10.1007/s10439-010-0228-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2010] [Accepted: 11/26/2010] [Indexed: 11/26/2022]
Abstract
To assess the effect of the perfusion pressure (PP) during machine perfusion (MP) on the preservation quality of kidney grafts, we compared mean PPs of 25 and 30 mmHg using a porcine autotransplantation model. After assessment of the microcirculation, animals underwent left nephrectomy. Thereafter, kidneys were washed out followed by 20 h of MP at 25 mmHg (MP25, n = 7) or 30 mmHg (MP30, n = 7) using a novel MP system for hypothermic pulsatile perfusion. After MP preservation, the contralateral kidneys were removed and the preserved kidneys heterotopically autotransplanted. Ten minutes after reperfusion, the microcirculation was reassessed. Seven days posttransplant, animals were euthanized and the kidney grafts removed for histological analysis. MP using a mean PP of 25 mmHg resulted in higher capillary blood flow after reperfusion. In the MP30 group, 6 out of 7 animals survived, whereas in the MP25 group all animals survived. Overall, improvement in recovery of renal function and a better preservation of structural integrity were seen in the MP25 group compared to the MP30 group. Using a novel system for hypothermic MP, a mean PP of 25 mmHg is preferred over a mean PP of 30 mmHg.
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Affiliation(s)
- B M Doorschodt
- Institute for Laboratory Animal Science and Experimental Surgery, RWTH-Aachen University, Pauwelsstrasse 30, Aachen, Germany
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Reznik O, Skvortsov A, Loginov I, Ananyev A, Bagnenko S, Moysyuk Y. Kidney from uncontrolled donors after cardiac death with one hour warm ischemic time: resuscitation by extracorporal normothermic abdominal perfusion "in situ" by leukocytes-free oxygenated blood. Clin Transplant 2010; 25:511-6. [PMID: 20973824 DOI: 10.1111/j.1399-0012.2010.01333.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The availability of brain death donors is restricted by many factors. Use of uncontrolled donors after cardiac death could be a promising perspective, but the limiting factor in uncontrolled donation after cardiac death is the warm ischemic time. The purpose of our work was to develop an in situ kidney preservation protocol with application of the extracorporal normothermic abdominal perfusion for organ resuscitation in uncontrolled donors after cardiac death. The main attention was paid to the elimination of leukocytes as the key damaging factor from modified donor oxygenated blood circulating in the device. In 2009, we had 10 uncontrolled donors with warm ischemic time from 45 to 92 min; a normothermic extracorporal perfusion device was applied, providing preservation and restoration of kidney after ischemic damage. In 6 out of 20 kidney recipients, graft function was recovered immediately. All kidney grafts are functioning, and to the end of the third month, the average creatinine was 118.5 ± 19.9 mM. Treatment of ischemically damaged kidney by normothermic extracorporal perfusion with leukocyte depletion before procurement seems to be a challenging protocol for expanding donors' pool and demands further study.
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Affiliation(s)
- Oleg Reznik
- Transplant Department, St. Petersburg State Research Institute for Emergency, St. Petersburg, Russia.
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Reznik O, Bagnenko S, Scvortsov A, Loginov I, Ananyev A, Senchik K, Moysyuk Y. The use of in-situ normothermic extracorporeal perfusion and leukocyte depletion for resuscitation of human donor kidneys. Perfusion 2010; 25:343-8. [DOI: 10.1177/0267659110377817] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The unexploited potential of donors after cardiac death is an actual issue for all countries where organ transplantation is performed. The crucial point in uncontrolled donation after cardiac death is the warm ischemic time. The primary purpose of our work was to define the limits of warm ischemic time. Another purpose was the development of an in situ kidney preservation protocol. In 8 uncontrolled donors with warm ischemic time from 45 to 91 minutes, a normothermic extracorporeal perfusion device was applied, providing preservation and restoration of the kidney after ischemic damage. Main attention was paid to the elimination of leukocytes as the key damaging factor from modified donor blood circulating in the device. In 6 out of 16 kidney recipients, graft function was recovered immediately and, by the end of the third month, the average creatinine was 117.9±21.9 mmol/L. Treatment of ischemically damaged kidneys by normothermic extracorporeal perfusion, with leukocyte depletion before procurement, seems to be a challenging protocol and demands further study. Implementation of perfusion systems in organ procurement practice could lead to a partial solution in the organ deficit problem.
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Affiliation(s)
- Oleg Reznik
- Saint-Petersburg Russian Federation Saint-Petersburg State Research Institute for Emergency, Saint-Petersburg, Russia,
| | - Sergey Bagnenko
- Saint-Petersburg Russian Federation Saint-Petersburg State Research Institute for Emergency, Saint-Petersburg, Russia
| | - Andrei Scvortsov
- Saint-Petersburg Russian Federation Saint-Petersburg State Research Institute for Emergency, Saint-Petersburg, Russia
| | - Igor Loginov
- Saint-Petersburg Russian Federation Saint-Petersburg State Research Institute for Emergency, Saint-Petersburg, Russia
| | - Alexei Ananyev
- Saint-Petersburg Russian Federation Saint-Petersburg State Research Institute for Emergency, Saint-Petersburg, Russia
| | - Konstantin Senchik
- Saint-Petersburg Russian Federation Saint-Petersburg State Research Institute for Emergency, Saint-Petersburg, Russia
| | - Yan Moysyuk
- Shumakov Research Center of Transplantology, Moscow, Russia
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8
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Cabello Benavente R, Rodríguez Martínez D, Hernández Fernández C, del Cañizo López JF, Lledó García E. [Hystologic and hemodynamic aspects of warm ischemic graft in relation to the preservation method]. Actas Urol Esp 2008; 32:75-82. [PMID: 18411626 DOI: 10.1016/s0210-4806(08)73798-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
OBJECTIVE The non-heart-beating donor has been proposed as a solution to donor shortage for renal transplantation. Because the nature of such donors, the kidneys so derived have been damaged by primary warm ischemia (WI), and so potentially they may never function. Minimizing graft injury is especially important in case of transplantation form marginal donors because of a high rate of delayed graft function or primary nonfunction. The aim of this experimental study is to assess the structural and hemodynamic consequences of hypothermic perfusion (HP) versus cold storage (CS), in renal allograft after a period of WI. MATERIAL AND METHODS We used 20 mini-pigs. WI was achieved by vascular pedicle occlusion during 45 min. We divided organs in 4 groups: A (n=5), kidneys with WI and then transplanted; group B (n=5), grafts with WI and implanted after HP with Belzer solution in our computerized perfusion system. Group C-control, (n=5) transplanted without WI and D (n=5) with WI and 60 min of CS in UW-Viaspan solution. All the procedure was recorded by a computerized data system. Renal vascular resistance (RVR) and renal vascular flow (RVF) were automatically calculated by means of mathematical formulas after renal transplantation. Subsequently histological study was completed in all cases. RESULTS We observed two patterns after transplantation: (1). Initial increase of RVR with posterior decrease and increase of vascular flow: in organs with WI and HP prior to transplantation (group B) // organs transplanted without WI (group C-control). Electronic and conventional microscopy showed integrity of endothelial and tubule structure. (2). Initial decrease with posterior increase of RVR. Organs with WI (group A) // organs with WI and CS (group D). Structural study showed endothelial and tubule disruption. CONCLUSION In our experimental model machine perfusion preserves endothelial and tubule structure of kidneys with WI. After transplantation the hemodynamic pattern of grafts with WI and HP is similar to the control group (without WI and direct transplantation).
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Affiliation(s)
- R Cabello Benavente
- Servicio de Urologia-Unidad de Preservación Renal Experimental, Hospital General Universitario Gregorio Marañón, Madrid.
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9
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Le prélèvement sur donneurs à cœur arrêté dans le cadre de la greffe rénale. Nephrol Ther 2008; 4:5-14. [DOI: 10.1016/j.nephro.2007.07.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2007] [Revised: 07/24/2007] [Accepted: 07/24/2007] [Indexed: 11/23/2022]
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Isch DJ. In defense of the reverence of all life: Heideggerean dissolution of the ethical challenges of organ donation after circulatory determination of death. MEDICINE, HEALTH CARE, AND PHILOSOPHY 2007; 10:441-59. [PMID: 17473990 DOI: 10.1007/s11019-007-9053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2006] [Accepted: 02/22/2007] [Indexed: 05/15/2023]
Abstract
During the past 50 years since the first successful organ transplant, waiting lists of potential organ recipients have expanded exponentially as supply and demand have been on a collision course. The recovery of organs from patients with circulatory determination of death is one of several effective alternative approaches recommended to reduce the supply-and-demand gap. However, renewed debate ensues regarding the ethical management of the overarching risks, pressures, challenges and conflicts of interest inherent in organ retrieval after circulatory determination of death. In this article, the author claims that through the engagement of a Heideggerean existential phenomenological and hermeneutic framework what are perceived as ethical problems dissolve, including collapse of commitment to the dead donor rule. The author argues for a revisioned socially constructed conceptual and philosophical responsibility of humankind to recognize the limits of bodily finitude, to responsibly use the capacity of the transplantable organs, and to grant enhanced or renewed existence to one with diminished or life-limited capacity; thereby making the locus of ethical concern the donor-recipient as unitary ''life.'' What ethically matters in the life-cycle (life-world) of donor-recipient is the viability of the organs transplanted; thereby granting reverence to all life.
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Affiliation(s)
- D J Isch
- Hospital, Harris Methodist Fort Worth, Office of Ethics, 1301 Pennsylvania Avenue, Fort Worth, TX, 76104, USA.
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11
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Tagboto S, Griffiths AP. The evaluation of renal ischaemic damage: the value of CD10 monoclonal antibody staining and of biochemical assessments of tissue viability. BMC Clin Pathol 2007; 7:5. [PMID: 17531101 PMCID: PMC1890546 DOI: 10.1186/1472-6890-7-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2006] [Accepted: 05/26/2007] [Indexed: 11/10/2022] Open
Abstract
Background It is well recognised that there is often a disparity between the structural changes observed in the kidney following renal injury and the function of the organ. For this reason, we carried out studies to explore possible means of studying and quantifying the severity of renal ischaemic damage using a laboratory model. Methods To do this, freshly isolated rabbit kidney tissue was subjected to warm (37°C) or cold (1°C) ischaemia for 20 hours. Following this, the tissue was stained using Haematoxylin and Eosin (H+E), Periodic Schiff reagent (PAS) and the novel monoclonal antibody CD10 stain. Additionally, ischaemic damage to the kidneys was assessed by biochemical tests of tissue viability using formazan-based colorimetry. Results CD 10 antibody intensely stained the brush border of control kidney tissue with mild or no cytoplasmic staining. Cell injury was accompanied by a redistribution of CD10 into the lumen and cell cytoplasm. There was good correlation between a score of histological damage using the CD 10 monoclonal antibody stain and the biochemical assessment of viability. Similarly, a score of histological damage using traditional PAS staining correlated well with that using the CD10 antibody stain. In particular, the biochemical assay and the monoclonal antibody staining techniques were able to demonstrate the efficacy of Soltran (this solution is used cold to preserve freshly isolated human kidneys prior to transplantation) in preserving renal tissue at cold temperatures compared to other randomly selected solutions. Conclusion We conclude that the techniques described using the CD10 monoclonal antibody stain may be helpful in the diagnosis and assessment of ischaemic renal damage. In addition, biochemical tests of viability may have an important role in routine histopathological work by giving additional information about cellular viability which may have implications on the function of the organ.
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Affiliation(s)
- S Tagboto
- Department of Nephrology, University Hospital of North Staffordshire, Royal Infirmary, Princes Road, Hartshill, Stoke on Trent ST4 7NL, UK
| | - A Paul Griffiths
- Department of Histopathology, Morriston Hospital, Morriston, Swansea SA6 6NL, UK
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12
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de Vries B, Snoeijs MGJ, von Bonsdorff L, Ernest van Heurn LW, Parkkinen J, Buurman WA. Redox-active iron released during machine perfusion predicts viability of ischemically injured deceased donor kidneys. Am J Transplant 2006; 6:2686-93. [PMID: 16889604 DOI: 10.1111/j.1600-6143.2006.01510.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Redox-active iron, catalyzing the generation of reactive oxygen species, has been implicated in experimental renal ischemia-reperfusion injury. However, in clinical transplantation, it is unknown whether redox-active iron is involved in the pathophysiology of ischemic injury of non-heart-beating (NHB) donor kidneys. We measured redox-active iron concentrations in perfusate samples of 231 deceased donor kidneys that were preserved by machine pulsatile perfusion at our institution between May 1998 and November 2002 using the bleomycin detectable iron assay. During machine pulsatile perfusion, redox-active iron was released into the preservation solution. Ischemically injured NHB donor kidneys had significantly higher perfusate redox-active iron concentrations than heart-beating (HB) donor kidneys that were not subjected to warm ischemia (3.9 +/- 1.1 vs. 2.8 +/- 1.0 micromol/L, p = 0.001). Moreover, redox-active iron concentration was an independent predictor of post-transplant graft viability (odds ratio 1.68, p = 0.01) and added predictive value to currently available donor and graft characteristics. This was particularly evident in uncontrolled NHB donor kidneys for which there is the greatest uncertainty about transplant outcomes. Therefore, perfusate redox-active iron concentration shows promise as a novel viability marker of NHB donor kidneys.
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Affiliation(s)
- B de Vries
- Department of Surgery, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Academic Hospital Maastricht and Maastricht University, Maastricht, The Netherlands
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13
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Gok MA, Bhatti AA, Asher J, Gupta A, Shenton BK, Robertson H, Soomro NA, Talbot D. The effect of inadequate in situ perfusion in the non heart-beating donor. Transpl Int 2005; 18:1142-6. [PMID: 16162100 DOI: 10.1111/j.1432-2277.2005.00164.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
In situ aortic perfusion in the nonheart-beating donors (NHBD) is an important procedure to reduce primary warm ischaemic injury prior to formal donor organ retrieval. It allows an interim period to obtain donor family consent and theatre preparation. This study describes our experience of inadequate aortic perfusions resulting from difficult aortic cannulations and associated adverse outcome despite reasonable viability tests. Since 1998, all NHBD in our institution are perfused in situ using a double balloon triple lumen (DBTL) catheter inserted through a femoral artery cut-down procedure. The DBTL catheter is positioned with distal occlusive balloon at the aortic bifurcation using the "pull-back" technique, the proximal occlusive balloon lies above the renal arteries. This provides selective aortic perfusion in particular the kidneys. Venous decompression using a femoral vein catheter enables a "two-way infusion system". Pre-transplant viability status of retrieved kidneys is determined by measuring pressure/resistance characteristics to the flow and biochemical markers for ischaemic injury. There were 90 NHBD renal transplants performed from 72 donors. Three renal transplants were carried out from three donors of ineffective in situ perfusion secondary to cannulation difficulties. Femoral cannulation was difficult as a result of extensive atherosclerosis of donor vessels. The comparison of allograft outcome from effective and ineffective in situ perfusion of donors showed high rate of primary nonfunction (PNF) from ineffective perfusion (chi-squared, P < 0.0001). The cases demonstrated poor outcome from ineffective perfusion related to the cannulation difficulties. Therefore a strict policy should be taken in cases where aortic cannulation and perfusion is inadequate, despite pretransplant assessment. In these circumstances, the primary warm ischaemia time should be extended to include this period of ineffective perfusion.
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Affiliation(s)
- Muhammed A Gok
- Renal Transplant Unit, The Freeman Hospital, University of Newcastle-upon-Tyne, Framlington Place, NE7 7DN Newcastle-upon-Tyne, UK.
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14
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Schold JD, Kaplan B, Howard RJ, Reed AI, Foley DP, Meier-Kriesche HU. Are we frozen in time? Analysis of the utilization and efficacy of pulsatile perfusion in renal transplantation. Am J Transplant 2005; 5:1681-8. [PMID: 15943626 DOI: 10.1111/j.1600-6143.2005.00910.x] [Citation(s) in RCA: 136] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Preservation techniques are crucial to deceased donor kidney transplantation (DDTx), but the efficacy of pulsatile perfusion (PP) versus cold storage (CS) remains uncertain. We describe patterns of PP use and explore four fundamental questions. What kidneys are selected for PP? How does PP affect utilization of donated kidneys? What effect does PP have on outcomes? When does PP appear to be most efficacious? We examined rates of PP in DDTx in the United States from 1994 to 2003. We generated models for organ utilization, delayed graft function (DGF) and for the use of PP. We analyzed the long-term effect of PP with multivariate Cox models. The utilization rates for non-expanded criteria donors (ECDs) were similar by storage type, but for ECDs there was a significantly higher utilization rate with PP (70% with PP vs. 59% with CS, p < 0.001). Use of PP was widely variable across transplant centers. DGF rates were significantly lower with PP (27.6% vs. 19.6%). PP was associated with a mild benefit on death censored graft survival (adjusted hazard ratio = 0.88, 95% CI 0.85-0.91). Reduced DGF and significantly lower discard rates of ECDs associated with PP suggest an important utility of PP in renal transplantation. Additional evidence of improvement in graft survival, particularly in more recent years, provides further encouraging evidence for the use of PP.
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Affiliation(s)
- Jesse D Schold
- Department of Medicine, University of Florida, Gainesville, FL, USA.
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Abstract
In recent years over 30% of cadaver donors utilized in the Emilia Romagna (ER) region are over 60 years of age often with some additional risk factors. The organs of these Suboptimal Kidney Donors (SOKD) had been seldomly accepted from 1996 to 1999 (Group 1). From 2000, marking the beginning of use of double transplantation for marginal kidneys, a routine biopsy was performed for SOKD using the Score System proposed by Remuzzi. (Group 2) The 40% of marginal kidneys harvested were utilize in 76% of cases. The few biopsies available for Group 1 patients testify that good kidneys had been discarded, but even in Group 2, when we followed the biopsy Score, strictly several mistakes were suspected: kidneys discarded for an unbelievable difference of 2 points between two kidneys of the same size, cases with an high score based on only a few glomeruli, double kidney transplants that become single and still had fair functions. In the future the utilization of SOKD should probably be improved: (1) with scores only based on a biopsy specimen with more than 25 glomeruli, (2) a score system for incorporating clinical data, and (3) continuous perfusion preservation of kidneys whose characteristics provide some more information that may mitigate some of the damage of marginal donor kidneys.
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Affiliation(s)
- A Faenza
- Dipartimento di Discipline Chirurgiche, Rianimatorie e dei Trapianti, Università di Bologna., Bologna, Italy
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Gok MA, Pelzers M, Glatz JFC, Shenton BK, Buckley PE, Peaston R, Cornell C, Mantle D, Soomro N, Jaques BC, Manas DM, Talbot D. Do tissue damage biomarkers used to assess machine-perfused NHBD kidneys predict long-term renal function post-transplant? Clin Chim Acta 2003; 338:33-43. [PMID: 14637263 DOI: 10.1016/j.cccn.2003.07.023] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Renal transplantation in many units is limited by the availability of donor organs. Kidneys obtained from non-heart-beating donors (NHBD) represent an important resource, with the potential to substantially increase the available donor organ pool. Such kidneys are associated with increased warm ischaemic tissue injury which may be assessed by hypothermic machine perfusion. Within our transplant centre, a key component of such damage assessment and viability screening involves the quantification of the tissue damage biomarkers glutathione S-transferase in kidney perfusates. METHODS Since 1998, 126 NHBD kidneys were machine-perfused prior to implantation, resulting in 74 transplants. Kidney perfusate samples were assayed for glutathione S-transferase in "real time", and alanine aminopeptidase and fatty acid binding protein in "retrospect". RESULTS The pre-transplant concentration of these tissue injury biomarkers determined pre-transplant did not correlate with subsequent longer-term renal function, as assessed by measurement of serum creatinine (tGST: Spearman correlation r=-0.02; Ala-AP: r=0.02; H-FABP: r=-0.05) and creatinine clearance (tGST: r=0.08; Ala-AP: r=-0.02; H-FABP: r=0.14) for those kidneys that had passed their viability tests. CONCLUSIONS Thus whilst these biomarkers may represent reliable pre-transplant indicators of immediate kidney viability and short-term kidney function, they do not predict the efficacy of renal function in the longer term.
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Affiliation(s)
- Muhammed A Gok
- Renal/Liver Transplant Unit, The Freeman Hospital, University of Newcastle Upon Tyne, Level 5, NE7 7DN, Newcastle Upon Tyne, England, UK.
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Sudhindran S, Pettigrew GJ, Drain A, Shrotri M, Watson CJE, Jamieson NV, Bradley JA. Outcome of transplantation using kidneys from controlled (Maastricht category 3) non-heart-beating donors. Clin Transplant 2003; 17:93-100. [PMID: 12709073 DOI: 10.1034/j.1399-0012.2003.00014.x] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND Many renal transplant centres are reluctant to use kidneys from non-heart-beating (NHB) donors because of the high incidence of primary non-function and delayed graft function reported in the literature. Here, we report our favourable experience of using kidneys from Maastricht category 3 donors (controlled NHB donors). MATERIALS AND METHODS From January 1996 to June 2002, 42 renal transplants using kidneys from 25 controlled NHB donors were undertaken at our centre. The rates of primary non-function, delayed graft function (DGF), rejection and long-term graft and patient survival were compared with those of 84 recipients of grafts from heart-beating (HB donors) transplanted contemporaneously. RESULTS Primary non-function did not occur in recipients of grafts from NHB donors but was seen in two grafts from HB donors. DGF occurred in 21 of 42 (50%) kidneys from NHB donors and 14 of 84 (17%) kidneys from HBD donars (p < 0.001). The acute rejection rates in the two groups were similar (33% for grafts from NHB donors vs. 40% from HB donors). By 1 month after transplantation, there was no significant difference in serum creatinine concentration between the two groups. Over a median follow-up period of 32 months (range 2-75 months), the actuarial graft survival rates at 1, 3 and 5 yr after transplantation were 84, 80 and 74% for recipients of kidneys from NHB donors, compared with 89, 85 and 80% for kidneys from HB donors. CONCLUSION Controlled NHB donors are a valuable and under-used source of kidneys for renal transplantation. The outcome for recipients of kidney allografts from category 3 NHB donors is similar to that seen in recipients of grafts from conventional HB cadaveric donors.
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Affiliation(s)
- S Sudhindran
- University Department of Surgery, Addenbrooke's Hospital, Cambridge, UK
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Burgos FJ, Alcaraz A, Castillón I, González Martín M, Lledó E, Matesanz R, Marcén R, Montañés P, Pascual J. [Present and future of kidney transplantation]. Actas Urol Esp 2002; 26:731-58. [PMID: 12645371 DOI: 10.1016/s0210-4806(02)72853-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Renal transplant is the treatment of choice for the patient with end stage renal disease. Spain is the country with the highest donation rate (33 ppm). However, at present this figure is stabilized. The development of non-beating heart programmes, living-donor nephrectomy (specially laparoscopic nephrectomy) programmes, and may be xenotransplantation in a non-immediate future could increase the transplantation activity. The knowledge of preservation mechanisms, specially with the use of perfusion machines allows to rescue for transplantation kidneys with a long warm-ischemia time. Furthermore, these machines are useful for analyzing viability markers. The new immunosuppressive drugs: Tacrolimus, Mycophenolate-Mophetil, Rapamycin and monoclonal antibodies against alpha chain of the interleukine-2 receptor (Basoliximab and Dazcizumab) have reduced the incidence of acute rejection in the immediate renal transplant period. However, its effect in the long-term follow-up period is still a matter of controversy. The incidence of tumour in the renal transplant recipient is increased, specially those of lymphoma, skin cancer and Kaposi sarcoma. Periodical exams for detecting the development of tumours are mandatory in this population. Finally, xenotransplantation is an attractive alternative, although immunological, infective and ethical barriers should previously be resolved.
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Affiliation(s)
- F J Burgos
- Servicio de Urología, Hospital Ramón y Cajal, Universidad Alcalá, Madrid
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19
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Abstract
The clinical boundaries of transplantation have been set in an era of simple cold storage. Research in organ preservation has led to the development of flush solutions that buffer the harsh molecular conditions which develop during ischaemia, and provide stored organs that are fit to sustain life after transplantation. Although simple and efficient, this method might be reaching its limit with respect to the duration, preservation, and the quality of organs that can be preserved. In addition, flush preservation does not allow for adequate viability assessment. There is good evidence that preservation times will be extended by the provision of continuous cellular substrate. Stimulation of in-vivo conditions by ex-vivo perfusion could also mean that marginal organs will be salvaged for transplantation. Perfusion will also allow for assessing the viability of organs before transplantation in a continuous fashion. The cumulative effect of these benefits would include expansion of the donor pool, less risk of primary non-function, and extension of the safe preservation period. Use of non-heart-beating donors, international organ sharing, and precise calculation of the risk of primary organ failure could become standard.
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Affiliation(s)
- Shawn D St Peter
- Nuffield Department of Surgery, John Radcliffe Hospital, University of Oxford, OX3 9DU, Oxford, UK
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20
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St. Peter SD, Imber CJ, Cenarruzabeitia ILD, Friend PJ. The non-heart-beating donor: Bridging the gap to the future. Transplant Rev (Orlando) 2002. [DOI: 10.1053/trre.2002.28974] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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