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Zhang F, Liang J, Xiong Y, Zhang F, Wu K, Wang W, Yuan J, Lin T, Wang X. Serum uric acid as a risk factor for rejection after deceased donor kidney transplantation: A mono-institutional analysis of paired kidneys. Front Immunol 2022; 13:973425. [PMID: 36578496 PMCID: PMC9791182 DOI: 10.3389/fimmu.2022.973425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/23/2022] [Indexed: 12/14/2022] Open
Abstract
Background Deceased donor kidney transplantation (DDKT) is a major therapeutic option for patients with end-stage renal diseases. Although medical techniques improved in recent years, acute or chronic rejection after DDKT is not uncommon and often results in poor graft survival. Therefore, the determination of risk factors is very important to stratify patients and to improve outcomes. This study aims to evaluate the risk factors for treated rejection (TR) of patients after DDKT. Methods Clinical data of deceased donors and corresponding recipients were retrospectively collected. The primary outcome was TR defined as the treatment for rejection within 24 months after DDKT. Univariate comparisons of baseline characteristics were performed with Chi-square test, t-test, and Mann-Whitney U test. Logistic regression was constructed to analyze potential risk factors. Receiver operating characteristic (ROC) curve and Jordan index were generated to determine the optimal cutoff value. The association between continuous variables and TR was examined and visualized by using restricted cubic spline (RCS) models. Results Data of 123 deceased donors and 246 recipients were obtained and analyzed. The median age was 41 (4-62) years for recipients and 39 (1-65) years for donors. The recipients who died or suffered graft loss during the follow-up period were 8 (3.3%) and 12 (4.9%), respectively. After univariate analysis and subsequent multivariate analysis, the preoperative serum uric acid (OR, 2.242; 95% CI, 1.037-4.844; P = 0.040), platelet (OR, 2.163; 95% CI, 1.073-4.361, P = 0.031), absolute neutrophil count (OR, 2.183; 95% CI, 1.025-4.649; P = 0.043), and HLA-DQ mismatch (OR, 2.102; 95% CI, 1.093-4.043; P = 0.026) showed statistical significance. RCS models showed that patients with higher levels of uric acid had increased risk of TR. Conclusions Serum uric acid and other three indicators were found to be the independent risk factors for TR, which may contribute to stratify patients and develop personalized regimen in perioperative period.
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Argani H. Cardiopulmonary death donation. TRANSPLANTATION REPORTS 2022. [DOI: 10.1016/j.tpr.2022.100104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
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Wu DA, Oniscu GC. Piloting Uncontrolled DCD Organ Donation in the UK; Overview, Lessons and Future Steps. CURRENT TRANSPLANTATION REPORTS 2022. [DOI: 10.1007/s40472-022-00374-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
Abstract
Purpose of Review
We explore how to develop Maastricht category I and II donation in the UK. We discuss lessons learned from previous UK pilots and define future steps in the journey to establishing a sustainable uDCD programme in the UK.
Recent Findings
The emergence of normothermic regional perfusion (NRP) as a successful strategy in cDCD donation with excellent clinical results creates the optimal platform for the development of a uDCD programme. Coordinated logistics with ambulance services and ED departments, embedded donor coordination in ED, public acceptance and wider discussion on acceptable peri-mortem interventions are key for future developments.
Summary
A uDCD programme in the UK is feasible. Despite an increase in public awareness and recent changes in legislation, there remain several challenges. Recent advances in perfusion and preservation and an established national retrieval infrastructure, create the premises for future sustainable developments.
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Kizilbash SJ, Evans MD, Chavers BM. Survival Benefit of Donation After Circulatory Death Kidney Transplantation in Children Compared With Remaining on the Waiting List for a Kidney Donated After Brain Death. Transplantation 2022; 106:575-583. [PMID: 33654002 PMCID: PMC8408288 DOI: 10.1097/tp.0000000000003733] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Kidneys donated after circulatory death (DCD) are increasingly being used for transplantation in adults to alleviate organ shortage. Pediatric data on survival benefits of DCD transplantation compared with remaining on the waitlist for a kidney donated after brain death (DBD) offer are lacking. METHODS We used Scientific Registry of Transplant Recipients to identify 285 pediatric (<18 y) DCD kidney transplants performed between 1987 and 2017. Propensity score matching was used to create a comparison group of 1132 DBD transplants. We used sequential Cox analysis to evaluate survival benefit of DCD transplantation versus remaining on the waitlist and Cox regression to evaluate patient and graft survival. RESULTS DCD transplantation was associated with a higher incidence of delayed graft function (adjusted odds ratio: 3.0; P < 0.001). The risks of graft failure (adjusted hazard ratio [aHR], 0.89; P = 0.46) and death (aHR, 1.2; P = 0.67) were similar between DCD and DBD recipients. We found a significant survival benefit of DCD transplantation compared with remaining on the waitlist awaiting a DBD kidney (aHR, 0.44; P = 0.03). CONCLUSIONS Despite a higher incidence of delayed graft function, long-term patient and graft survival are similar between pediatric DCD and DBD kidney transplant recipients. DCD transplantation in children is associated with a survival benefit, despite pediatric priority for organ allocation, compared with remaining on the waitlist.
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Affiliation(s)
| | - Michael D Evans
- Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN
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5
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Yahyazadeh SR, Naderi G, Zadeh SST, Saatchi M, Khatami F, Aghamir SMK. Comparative study of the outcomes of the second kidney transplantation from the young deceased donors versus living-unrelated donors. Transpl Immunol 2022; 71:101527. [PMID: 34998989 DOI: 10.1016/j.trim.2022.101527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 01/01/2022] [Accepted: 01/01/2022] [Indexed: 11/19/2022]
Abstract
PURPOSE To compare the kidney graft function and survival in patients who had second kidney transplantation from living donors versus those who had a second transplant from young deceased donors. METHODS In this retrospective cohort study, a total of 86 patients who underwent second kidney transplantation in Shariati hospital from 2001 until 2017 were enrolled. Baseline clinical data on the age, sex, type of kidney donor (living unrelated or deceased), duration of pretransplant dialysis, and the length of hospitalization were recorded. As the indicators of the graft function, we used the serum creatinine level and estimated glomerular filtration rate (eGFR) at time intervals during the study. The 1, 5, and 10-year graft survival rates were reported using life tables and the relative hazard ratios of the graft failure were calculated using the forward stepwise Cox proportional hazard model. RESULTS Forty-six of our patients were men (53.5%), with a mean ± SD age of 44.3 ± 12.3 years at the time of transplantation. The majority of the enrolled patients received the kidney from living unrelated donors (50 vs. 36 patients). In terms of serum creatinine and eGFR, at time intervals, no significant difference was found between the two recipient groups. In the living donor group, the 1, 5, and 10-year graft survival rates of the second transplant were 91% (95%CI: 73-96%), 87% (95%CI: 69-95%), and 82% (95%CI: 59-92%), and for the deceased donor group were 95% (95% CI: 69-99%), 95% (95%CI: 69-99%), and 79% (95%CI: 31-95%), respectively. CONCLUSION Considering the long-term outcomes of the second kidney transplantation, in our experience, the graft function and survival, either from the living or deceased donors, were favorable; and the type of organ donation had no significant effect on the risk of graft failure.
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Affiliation(s)
- Seyed Reza Yahyazadeh
- Shariati Hospital, Department of Urology, Tehran University of Medical Sciences, Tehran, Iran
| | - Gholamhossein Naderi
- Shariati Hospital, Department of Urology, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Saatchi
- Department of Epidemiology and Biostatistics, School of Public Health(,) Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Khatami
- Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Balani SS, Jensen CJ, Kouri AM, Kizilbash SJ. Induction and maintenance immunosuppression in pediatric kidney transplantation-Advances and controversies. Pediatr Transplant 2021; 25:e14077. [PMID: 34216190 DOI: 10.1111/petr.14077] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 05/04/2021] [Accepted: 05/26/2021] [Indexed: 12/16/2022]
Abstract
Advances in immunosuppression have improved graft survival in pediatric kidney transplant recipients; however, treatment-related toxicities need to be balanced against the possibility of graft rejection. Several immunosuppressive agents are available for use in transplant recipients; however, the optimal combinations of agents remain unclear, resulting in variations in institutional protocols. Lymphocyte-depleting antibodies, specifically ATG, are the most common induction agent used for pediatric kidney transplantation in the US. Basiliximab may be used for induction in immunologically low-risk children; however, pediatric data are scarce. CNIs and antiproliferative agents (mostly Tac and mycophenolate in recent years) constitute the backbone of maintenance immunosuppression. Steroid-avoidance maintenance regimens remain controversial. Belatacept and mTOR inhibitors are used in children under specific circumstances such as non-adherence or CNI toxicity. This article reviews the indications, mechanism of action, efficacy, dosing, and side effect profiles of various immunosuppressive agents available for pediatric kidney transplantation.
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Affiliation(s)
- Shanthi S Balani
- Pediatric Nephrology, University of Minnesota, Minneapolis, MN, USA
| | - Chelsey J Jensen
- Solid Organ Transplant, University of Minnesota, Minneapolis, MN, USA
| | - Anne M Kouri
- Pediatric Nephrology, University of Minnesota, Minneapolis, MN, USA
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Hosgood SA, Brown RJ, Nicholson ML. Advances in Kidney Preservation Techniques and Their Application in Clinical Practice. Transplantation 2021; 105:e202-e214. [PMID: 33982904 PMCID: PMC8549459 DOI: 10.1097/tp.0000000000003679] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 12/03/2020] [Accepted: 12/15/2020] [Indexed: 11/25/2022]
Abstract
The use of cold preservation solutions to rapidly flush and cool the kidney followed by static cold storage in ice has been the standard kidney preservation technique for the last 50 y. Nonetheless, changing donor demographics that include organs from extended criteria donors and donation after circulatory death donors have led to the adoption of more diverse techniques of preservation. Comparison of hypothermic machine perfusion and static cold storage techniques for deceased donor kidneys has long been debated and is still contested by some. The recent modification of hypothermic machine perfusion techniques with the addition of oxygen or perfusion at subnormothermic or near-normothermic temperatures are promising strategies that are emerging in clinical practice. In addition, the use of normothermic regional perfusion to resuscitate abdominal organs of donation after circulatory death donors in situ before cold flushing is also increasingly being utilized. This review provides a synopsis of the different types of preservation techniques including their mechanistic effects and the outcome of their application in clinical practice for different types of donor kidney.
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Affiliation(s)
- Sarah A. Hosgood
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
| | - Rachel J. Brown
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
| | - Michael L. Nicholson
- Department of Surgery, University of Cambridge, Addenbrooke’s Hospital, Cambridge, United Kingdom
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Implementation of donation after circulatory death kidney transplantation can safely enlarge the donor pool: A systematic review and meta-analysis. Int J Surg 2021; 92:106021. [PMID: 34256169 DOI: 10.1016/j.ijsu.2021.106021] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2021] [Revised: 06/14/2021] [Accepted: 07/08/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Donation after circulatory death (DCD) kidney transplantation has been introduced to address organ shortage. However, DCD kidneys are not accepted worldwide due to concerns about inferior quality. To investigate whether these concerns are justified, we performed a systematic review and meta-analysis to investigate DCD graft outcomes compared to donation after brain death (DBD). MATERIALS AND METHODS EMBASE, Medline, Cochrane, Web of Science and Google Scholar were searched from database inception until September 2020. Exclusion criteria were studies reporting on pediatric/dual kidney transplants, multi-organ transplants or studies including normothermic perfusion techniques. The primary outcome was graft survival. Secondary outcomes were primary non-function (PNF), delayed graft function (DGF), 3-months biopsy-proven acute rejection (BPAR), 1-year estimated Glomerular Filtration Rate (eGFR), patient survival, and urologic complications. A random-effects model was used for meta-analysis. Meta-regression analysis was performed in case of high between-study heterogeneity. RESULTS Fifty-one studies were included, comprising 73,454 DCD and 518,229 DBD recipients. One-year graft loss was increased in DCD recipients (death-censored: risk ratio (RR) 1.10 (95%-confidence interval (CI) 1.04-1.16), all-cause: RR 1.13 (95%-CI 1.08-1.19)). Ten-year graft loss was similar to DBD (death-censored: RR 1.02 (95%-CI 0.92-1.13), all-cause: RR 1.03 (95%-CI 0.94-1.13)). DCD recipients had an increased risk of PNF (RR 1.43 (95%-CI 1.26-1.62)), DGF (RR 2.02 (95%-CI 1.88-2.16)), and 1-year mortality (RR 1.10 (95%-CI 1.01-1.21)). No differences were observed for 3-months BPAR, ureter stenosis/leakage, 1-year eGFR and 10-year mortality. CONCLUSION Long-term DCD kidney transplant outcomes are similar to DBD despite a higher risk of PNF, DGF, and a 13% increased risk of graft loss in the first year after transplantation. These results should encourage implementation of DCD programs.
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9
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Kidney transplantation following uncontrolled donation after circulatory death. Curr Opin Organ Transplant 2020; 25:144-150. [DOI: 10.1097/mot.0000000000000742] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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10
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Heylen L, Pirenne J, Samuel U, Tieken I, Coemans M, Naesens M, Sprangers B, Jochmans I. Effect of donor nephrectomy time during circulatory-dead donor kidney retrieval on transplant graft failure. Br J Surg 2019; 107:87-95. [DOI: 10.1002/bjs.11316] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2019] [Revised: 05/05/2019] [Accepted: 06/27/2019] [Indexed: 01/12/2023]
Abstract
Abstract
Background
When the blood supply ceases in a deceased organ donor, ischaemic injury starts. Kidneys are cooled to reduce cellular metabolism and minimize ischaemic injury. This cooling is slow and kidneys are lukewarm during nephrectomy. Smaller single-centre studies have shown that prolonged donor nephrectomy time decreases early kidney transplant function, but the effect on long-term outcome has never been investigated in large multicentre cohort studies.
Methods
The relationship between donor nephrectomy time and death-censored graft survival was evaluated in recipients of single adult-to-adult, first-time deceased-donor kidneys transplanted in the Eurotransplant region between 2004 and 2013.
Results
A total of 13 914 recipients were included. Median donor nephrectomy time was 51 (i.q.r. 39–65) min. Kidneys donated after circulatory death had longer nephrectomy times than those from brain-dead donors: median 57 (43–78) versus 50 (39–64) min respectively (P < 0·001). Donor nephrectomy time was independently associated with graft loss when kidneys were donated after circulatory death: adjusted hazard ratio (HR) 1·05 (95 per cent c.i. 1·01 to 1·09) per 10-min increase (P = 0·026). The magnitude of this effect was comparable to the effect of each hour of additional cold ischaemia: HR 1·04 (1·01 to 1·07) per h (P = 0·004). For kidneys donated after brain death, there was no effect of nephrectomy time on graft survival: adjusted HR 1·01 (0·98 to 1·04) per 10 min (P = 0·464).
Conclusion
Prolonged donor nephrectomy time impairs graft outcome in kidneys donated after circulatory death. Keeping this short, together with efficient cooling during nephrectomy, might improve outcome.
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Affiliation(s)
- L Heylen
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
| | - J Pirenne
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
- Abdominal Transplantation, Transplantation Research Group, KU Leuven, Leuven, Belgium
| | - U Samuel
- Eurotransplant International Foundation, Leiden, the Netherlands
| | - I Tieken
- Eurotransplant International Foundation, Leiden, the Netherlands
| | - M Coemans
- Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium
| | - M Naesens
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
- Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium
| | - B Sprangers
- Department of Nephrology, University Hospitals Leuven, Leuven, Belgium
- Molecular Immunology, Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium
| | - I Jochmans
- Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium
- Abdominal Transplantation, Transplantation Research Group, KU Leuven, Leuven, Belgium
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Sánchez-Fructuoso AI, Pérez-Flores I, Del Río F, Blázquez J, Calvo N, Moreno de la Higuera MÁ, Gómez A, Alonso-Lera S, Soria A, González M, Corral E, Mateos A, Moreno-Sierra J, Fernández Pérez C. Uncontrolled donation after circulatory death: A cohort study of data from a long-standing deceased-donor kidney transplantation program. Am J Transplant 2019; 19:1693-1707. [PMID: 30589507 DOI: 10.1111/ajt.15243] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2018] [Revised: 11/29/2018] [Accepted: 12/10/2018] [Indexed: 01/25/2023]
Abstract
Despite good long-term outcomes of kidney transplants from controlled donation after circulatory death (DCD) donors, there are few uncontrolled DCD (uDCD) programs. This longitudinal study compares outcomes for all uDCD (N = 774) and all donation after brain death (DBD) (N = 613) kidney transplants performed from 1996 to 2015 at our center. DBD transplants were divided into those from standard-criteria (SCD) (N = 366) and expanded-criteria (N = 247) brain-dead donors (ECD). One-, 5-, and 10-year graft survival rates were 91.7%, 85.7%, and 80.6% for SCD; 86.0%, 75.8%, and 61.4% for ECD; and 85.1%, 78.1%, and 72.2% for uDCD, respectively. Graft survival was worse in recipients of uDCD kidneys than of SCD (P = .004) but better than in transplants from ECD (P = .021). The main cause of graft loss in the uDCD transplants was primary nonfunction. Through logistic regression, donor death due to pulmonary embolism (OR 4.31, 95% CI 1.65-11.23), extrahospital CPR time ≥75 minutes (OR1.94, 95%CI 1.18-3.22), and in-hospital CPR time ≥50 minutes (OR 1.79, 95% CI 1.09-2.93) emerged as predictive factors of primary nonunction. According to the outcomes of our long-standing kidney transplantation program, uDCD could help expand the kidney donor pool.
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Affiliation(s)
| | - Isabel Pérez-Flores
- Nephrology Department, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
| | - Francisco Del Río
- Transplantation Coordination Unit, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
| | - Jesús Blázquez
- Urology Department, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
| | - Natividad Calvo
- Nephrology Department, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
| | | | - Angel Gómez
- Urology Department, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
| | - Santiago Alonso-Lera
- Surgery Department, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
| | - Ana Soria
- Transplantation Coordination Unit, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
| | - Manuel González
- Transplantation Coordination Unit, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
| | | | - Alonso Mateos
- SUMMA112, School of Medicine, Francisco de Vitoria University, Madrid, Spain
| | - Jesús Moreno-Sierra
- Transplantation Coordination Unit, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain
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12
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Xu M, Garcia-Aroz S, Banan B, Wang X, Rabe BJ, Zhou F, Nayak DK, Zhang Z, Jia J, Upadhya GA, Manning PT, Gaut JP, Lin Y, Chapman WC. Enhanced immunosuppression improves early allograft function in a porcine kidney transplant model of donation after circulatory death. Am J Transplant 2019; 19:713-723. [PMID: 30152136 DOI: 10.1111/ajt.15098] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 07/30/2018] [Accepted: 08/14/2018] [Indexed: 01/25/2023]
Abstract
It remains controversial whether renal allografts from donation after circulatory death (DCD) have a higher risk of acute rejection (AR). In the porcine large animal kidney transplant model, we investigated the AR and function of DCD renal allografts compared to the non-DCD renal allografts and the effects of increased immunosuppression. We found that the AR was significantly increased along with elevated MHC-I expression in the DCD transplants receiving low-dose immunosuppression; however, AR and renal function were significantly improved when given high-dose immunosuppressive therapy postoperatively. Also, high-dose immunosuppression remarkably decreased the mRNA levels of ifn-g, il-6, tgf-b, il-4, and tnf-a in the allograft at day 5 and decreased serum cytokines levels of IFN-g and IL-17 at day 4 and day 5 after operation. Furthermore, Western blot analysis showed that higher immunosuppression decreased phosphorylation of signal transducer and activator of transcription 3 and nuclear factor kappa-light-chain-enhancer of activated B cells-p65, increased phosphorylation of extracellular-signal-regulated kinase, and reduced the expression of Bcl-2-associated X protein and caspase-3 in the renal allografts. These results suggest that the DCD renal allograft seems to be more vulnerable to AR; enhanced immunosuppression reduces DCD-associated AR and improves early allograft function in a preclinical large animal model.
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Affiliation(s)
- Min Xu
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
| | - Sandra Garcia-Aroz
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
| | - Babak Banan
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
| | - Xuanchuan Wang
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA.,Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Brian J Rabe
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
| | - Fangyu Zhou
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
| | - Deepak K Nayak
- University of Arizona College of Medicine-Phoenix, Phoenix, AZ, USA
| | - Zhengyan Zhang
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
| | - Jianluo Jia
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
| | - Gundumi A Upadhya
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
| | | | - Joseph P Gaut
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA
| | - Yiing Lin
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
| | - William C Chapman
- Department of Surgery, Section of Abdominal Transplantation, Washington University School of Medicine, St. Louis, MO, USA
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Abstract
PURPOSE OF REVIEW Donation after circulatory death (DCD) is still performed in a limited number of countries. This article summarizes the development of DCD in Spain and presents recent Spanish contributions to gain knowledge on the potential benefits and the practical use of normothermic regional perfusion (nRP). RECENT FINDINGS DCD now contributes to 24% of deceased donors in Spain. The development of DCD has been based on an assessment of practices in the treatment of cardiac arrest and end-of-life care to accommodate the option of DCD; the creation of an adequate regulatory framework; and institutional support, professional training and public education. Appropriate posttransplant outcomes have been obtained with organs from both uncontrolled and controlled DCD donors. nRP is increasingly used, with preliminary data supporting improved results compared with other in-situ preservation/recovery approaches. Mobile teams with portable extracorporeal membrane oxygenation devices are making nRP possible in hospitals without these resources. To avoid the possibility of reestablishing brain circulation after the determination of death, a specific methodology has been validated. SUMMARY DCD has been successfully developed in Spain following a streamlined process. nRP may become a standard in DCD, although further evidence on the benefits of this technology is eagerly awaited.
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14
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Molina M, Guerrero-Ramos F, Fernández-Ruiz M, González E, Cabrera J, Morales E, Gutierrez E, Hernández E, Polanco N, Hernández A, Praga M, Rodriguez-Antolín A, Pamplona M, de la Rosa F, Cavero T, Chico M, Villar A, Justo I, Andrés A. Kidney transplant from uncontrolled donation after circulatory death donors maintained by nECMO has long-term outcomes comparable to standard criteria donation after brain death. Am J Transplant 2019; 19:434-447. [PMID: 29947163 DOI: 10.1111/ajt.14991] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 06/22/2018] [Accepted: 06/22/2018] [Indexed: 01/25/2023]
Abstract
Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplant (KT) with short-term outcomes similar to those obtained from donation after brain death (DBD) donors. However, heterogeneous results in the long term have been reported. We compared 10-year outcomes between 237 KT recipients from uDCD donors maintained by normothermic extracorporeal membrane oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD donors during the same period at our institution. We further analyzed risk factors for death-censored graft survival in the uDCD group. Delayed graft function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P < .01), although glomerular filtration rates at the end of follow-up were similar in the 2 groups. uDCD and DBD groups had similar rates for 10-year death-censored graft (82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454). Donor age >50 years was associated with graft loss in the uDCD group (hazard ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant effect. uDCD KT under nECMO support resulted in similar graft function and long-term outcomes compared with KT from standard criteria DBD donors. Increased donor age could negatively affect graft survival after uDCD donation.
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Affiliation(s)
- María Molina
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Félix Guerrero-Ramos
- Department of Urology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Mario Fernández-Ruiz
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Esther González
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Jimena Cabrera
- Programa de Prevención y Tratamiento de las Glomerulopatías, Centro de Nefrología, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay.,Department of Nephrology, Hospital Evangelico, Montevideo, Uruguay
| | - Enrique Morales
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Eduardo Gutierrez
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Eduardo Hernández
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Natalia Polanco
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Ana Hernández
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Manuel Praga
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain.,School of Medicine, Universidad Complutense, Madrid, Spain
| | - Alfredo Rodriguez-Antolín
- Department of Urology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Manuel Pamplona
- Department of Urology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Federico de la Rosa
- Department of Urology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Teresa Cavero
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Mario Chico
- Department of Intensive Care Medicine, Hospital Universitario "12 de Octubre", Madrid, Spain
| | | | - Iago Justo
- Department of Abdominal Organ Transplantation and General and Digestive Surgery, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain
| | - Amado Andrés
- Department of Nephrology, Hospital Universitario "12 de Octubre", Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain.,School of Medicine, Universidad Complutense, Madrid, Spain
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15
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Del Río F, Andrés A, Padilla M, Sánchez-Fructuoso AI, Molina M, Ruiz Á, Pérez-Villares JM, Peiró LZ, Aldabó T, Sebastián R, Miñambres E, Pita L, Casares M, Galán J, Vidal C, Terrón C, Castro P, Sanroma M, Coll E, Domínguez-Gil B. Kidney transplantation from donors after uncontrolled circulatory death: the Spanish experience. Kidney Int 2018; 95:420-428. [PMID: 30579725 DOI: 10.1016/j.kint.2018.09.014] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2018] [Revised: 09/04/2018] [Accepted: 09/06/2018] [Indexed: 10/27/2022]
Abstract
Donation after uncontrolled circulatory death (uDCD) refers to donation from persons who have died following cardiac arrest and unsuccessful attempt at resuscitation. We report the Spanish experience of uDCD kidney transplantation, and identify factors related to short-term post-transplant outcomes. The Spanish CORE system compiles data on all donation and transplant procedures in the country. Between 2012-2015, 517 kidney transplants from 288 uDCD donors were performed. The incidence of primary non-function was 10%, and the incidence of delayed graft function was 76%. One-year death-censored graft survival was 87%. In a Cox-Model, donor age ≥ 60 years (odds ratio [OR] 2.7; 95% confidence interval [CI] 1.2-6.1), in situ cooling of kidneys versus normothermic regional perfusion (OR 5.6; 95% CI 2.7-11.5) or hypothermic regional perfusion based on the use of extracorporeal membrane oxygenation devices (OR 4.3; 95% CI 2.1-8.6), and a recipient history of prior kidney transplant (OR 3.5; 95% CI 1.5-8.3) all significantly increased the risk of graft loss during the first year after transplantation. Kidney transplantation from uDCD donors provides acceptable 1-year outcomes, although there is room for improvement. Hypothermic and normothermic regional perfusion strategies are preferable to in situ cooling of kidneys from uDCD donors.
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Affiliation(s)
| | - Amado Andrés
- Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | | | - María Molina
- Hospital Universitario 12 de Octubre, Madrid, Spain
| | | | | | | | - Teresa Aldabó
- Hospital Universitario Virgen del Rocío, Sevilla, Spain
| | | | | | - Lidia Pita
- Complejo Hospitalario Universitario A Coruña, La Coruña, Spain
| | | | - Juan Galán
- Hospital Universitario y Politécnico de la Fe, Valencia, Spain
| | | | | | - Pablo Castro
- Regional Coordination of the Autonomous Community of Andalucía, Sevilla, Spain
| | - Marga Sanroma
- Regional Coordination of the Autonomous Community of Cataluña, Barcelona, Spain
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16
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Broe MP, Galvin R, Keenan LG, Power RE. Laparoscopic and hand-assisted laparoscopic donor nephrectomy: A systematic review and meta-analysis. Arab J Urol 2018; 16:322-334. [PMID: 30140469 PMCID: PMC6104662 DOI: 10.1016/j.aju.2018.02.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 02/08/2018] [Indexed: 01/11/2023] Open
Abstract
Objective To compare the perioperative outcomes of hand-assisted laparoscopic donor nephrectomy (HALDN) and pure LDN, as HALDN and LDN are the two most widely used techniques of DN to treat end-stage renal disease. Methods In this systematic review and meta-analysis, we performed a literature search of PubMed, Embase, Web of Science, and Cochrane from 01/01/1995 to 31/12/2014. The primary outcome was conversion to an open procedure. Secondary outcomes were warm ischaemia time (WIT), operation time (OT), estimated blood loss (EBL), complications, and length of stay (LOS). Data analysed were presented as odds ratios (ORs) or weighted mean differences (WMDs) with 95% confidence intervals (CIs), I2, and P values. Subgroup analysis was performed. Results There were 24 studies included in the meta-analysis; three randomised controlled trials (RCTs), one randomised pilot study, two prospective, and 18 retrospective cohort studies. There were no differences in conversion to an open procedure between the two techniques for both RCTs (OR 0.42, 95% CI 0.06, 2.90; I2 = 0%, P < 0.001) and cohort studies (OR 1.06, 95% CI 0.63, 1.78; I2 = 0%, P = 0.84). WIT was shorter for the HALDN (-41.79 s, 95% CI -71.85, -11.74; I2 = 96%, P = 0.006), as was the OT (-26.32 min, 95% CI -40.67, -11.97; I2 = 95%, P < 0.001). There was no statistically significant difference in EBL, complications or LOS. Conclusion There is little statistical evidence to recommend one technique. HALDN is associated with a shorter WIT and OT. LDN has equal safety to HALDN. Further studies are required.
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Key Words
- (L)DN, (laparoscopic) donor nephrectomy
- BMI, body mass index
- EBL, estimated blood loss
- FEM, fixed-effects model
- HALDN, hand-assisted laparoscopic donor nephrectomy
- HARPDN, hand-assisted retroperitoneal donor nephrectomy
- Hand-assisted donor nephrectomy
- LOS, length of stay
- Laparoscopic donor nephrectomy
- OR, odds ratio
- OT, operation time
- PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-analyses
- RALDN, robot-assisted laparoscopic donor nephrectomy
- RCT, randomised controlled trial
- REM, random-effects model
- Renal transplantation
- WIT, warm ischaemia time
- WMD, weighted mean difference
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Affiliation(s)
- Mark P Broe
- Department of Urology and Renal Transplantation, Beaumont Hospital, Dublin, Ireland
| | - Rose Galvin
- Department of Postgraduate Studies, Royal College of Surgeons in Ireland, Dublin, Ireland
| | - Lorna G Keenan
- Department of Urology and Renal Transplantation, Beaumont Hospital, Dublin, Ireland
| | - Richard E Power
- Department of Urology and Renal Transplantation, Beaumont Hospital, Dublin, Ireland
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17
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Zhu D, McCague K, Lin W, Rong R, Xu M, Chan L, Zhu T. Outcome of Kidney Transplantation From Donor After Cardiac Death: Reanalysis of the US Mycophenolic Renal Transplant Registry. Transplant Proc 2018; 50:1258-1263. [DOI: 10.1016/j.transproceed.2018.01.051] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2017] [Revised: 12/17/2017] [Accepted: 01/23/2018] [Indexed: 12/19/2022]
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18
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Sun Q, Huang Z, Han F, Zhao M, Cao R, Zhao D, Hong L, Na N, Li H, Miao B, Hu J, Meng F, Peng Y, Sun Q. Allogeneic mesenchymal stem cells as induction therapy are safe and feasible in renal allografts: pilot results of a multicenter randomized controlled trial. J Transl Med 2018. [PMID: 29514693 PMCID: PMC5842532 DOI: 10.1186/s12967-018-1422-x] [Citation(s) in RCA: 57] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Kidneys from deceased donors are being used to meet the growing need for grafts. However, delayed graft function (DGF) and acute rejection incidences are high, leading to adverse effects on graft outcomes. Optimal induction intervention should include both renal structure injury repair and immune response suppression. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative, and immune-modulatory properties are considered a candidate to prevent DGF and acute rejection in renal transplantation. Thus, this prospective multicenter paired study aimed to assess the clinical value of allogeneic MSCs as induction therapy to prevent both DGF and acute rejection in deceased donor renal transplantation. METHODS Forty-two renal allograft recipients were recruited and divided into trial and control groups. The trial group (21 cases) received 2 × 106/kg human umbilical-cord-derived MSCs (UC-MSCs) via the peripheral vein before renal transplantation, and 5 × 106 cells via the renal artery during the surgical procedure. All recipients received standard induction therapy. Incidences of DGF and biopsy-proven acute rejection were recorded postoperatively and severe postoperative complications were assessed. Graft and recipient survivals were also evaluated. RESULTS Treatment with UC-MSCs achieved comparable graft and recipient survivals with non-MSC treatment (P = 0.97 and 0.15, respectively). No increase in postoperative complications, including DGF and acute rejection, were observed (incidence of DGF: 9.5% in the MSC group versus 33.3% in the non-MSC group, P = 0.13; Incidence of acute rejection: 14.3% versus 4.8%, P = 0.61). Equal postoperative estimated glomerular filtration rates were found between the two groups (P = 0.88). All patients tolerated the MSCs infusion without adverse clinical effects. Additionally, a multiprobe fluorescence in situ hybridization assay revealed that UC-MSCs administered via the renal artery were absent from the recipient's biopsy sample. CONCLUSIONS Umbilical-cord-derived MSCs can be used as clinically feasible and safe induction therapy. Adequate timing and frequency of UC-MSCs administration may have a significant effect on graft and recipient outcomes. Trial registration NCT02490020 . Registered on June 29 2015.
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Affiliation(s)
- Qipeng Sun
- Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Zhengyu Huang
- Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Fei Han
- Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Ming Zhao
- Department of Renal Transplantation, Zhujiang Hospital, Southern Medical University, Gongye Road 253, Guangzhou, 510280, People's Republic of China
| | - Ronghua Cao
- Department of Renal Transplantation, The Second Affiliated Hospital, Guangzhou Traditional Chinese Medicine University, Inner Ring Road 55, University City, Guangzhou, 510280, People's Republic of China
| | - Daqiang Zhao
- Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Liangqing Hong
- Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Ning Na
- Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Heng Li
- Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Bin Miao
- Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Jianmin Hu
- Department of Renal Transplantation, Zhujiang Hospital, Southern Medical University, Gongye Road 253, Guangzhou, 510280, People's Republic of China
| | - Fanhang Meng
- Department of Renal Transplantation, The Second Affiliated Hospital, Guangzhou Traditional Chinese Medicine University, Inner Ring Road 55, University City, Guangzhou, 510280, People's Republic of China
| | - Yanwen Peng
- Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People's Republic of China
| | - Qiquan Sun
- Department of Renal Transplantation, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.
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19
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Sun Q, Hong L, Huang Z, Na N, Hua X, Peng Y, Zhao M, Cao R, Sun Q. Allogeneic mesenchymal stem cell as induction therapy to prevent both delayed graft function and acute rejection in deceased donor renal transplantation: study protocol for a randomized controlled trial. Trials 2017; 18:545. [PMID: 29145879 PMCID: PMC5689202 DOI: 10.1186/s13063-017-2291-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2016] [Accepted: 10/30/2017] [Indexed: 12/12/2022] Open
Abstract
Background Using kidneys from deceased donors is an available strategy to meet the growing need of grafts. However, higher incidences of delayed graft function (DGF) and acute rejection exert adverse effects on graft outcomes. Since ischemia-reperfusion injury (IRI) and ongoing process of immune response to grafts are the major causes of DGF and acute rejection, the optimal induction intervention should possess capacities of both repairing renal structure injury and suppressing immune response simultaneously. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative and immune-modulatory properties are considered as a candidate to prevent both DGF and acute rejection in renal transplantation. Previous studies just focused on the safety of autologous MSCs on living-related donor renal transplants, and lack of concomitant controls and the sufficient sample size and source of MSCs. Here, we propose a prospective multicenter controlled study to assess the clinical value of allogeneic MSCs in preventing both DGF and acute rejection simultaneously as induction therapy in deceased-donor renal transplantation. Methods/design Renal allograft recipients (n = 100) will be recruited and divided into trial and control groups, and 50 patients in the trial group will be administered with a dose of 2 × 106 per kilogram human umbilical-cord-derived MSCs (UC-MSCs) via peripheral vein injection preoperatively, and a dose of 5 × 106 cells via renal arterial injection during surgery, with standard induction therapy. Incidences of postoperative DGF and biopsy-proved acute rejection (BPAR) will be recorded and analyzed. Additionally, other clinical parameters such as baseline demographics, graft and recipient survival and other severe postoperative complications, including complicated urinary tract infection, severe pneumonia, and severe bleeding, will be also assessed. Discussion This study will clarify the clinical value of UC-MSCs in preventing DGF and acute rejection simultaneously in deceased-donor renal transplantation, and provide evidence as to whether allogeneic MSCs can be used as clinically feasible and safe induction therapy. Trial registration ClinicalTrials.gov, NCT02490020. Registered on 29 June 2015. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2291-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Qipeng Sun
- Department of Renal Transplantation, Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Liangqing Hong
- Department of Renal Transplantation, Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Zhengyu Huang
- Department of Renal Transplantation, Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Ning Na
- Department of Renal Transplantation, Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Xuefeng Hua
- Department of Renal Transplantation, Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China
| | - Yanwen Peng
- Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Sun Yat-sen University, Tianhe Road 600, Guangzhou, 510630, People's Republic of China
| | - Ming Zhao
- Department of Renal Transplantation, Zhujiang Hospital, Southern Medical University, Gongye Road 253, Guangzhou, 510280, People's Republic of China
| | - Ronghua Cao
- Department of Renal Transplantation, The Second Affiliated Hospital, Guangzhou Traditional Chinese Medicine University, Inner Ring Road 55, University City, Guangzhou, 510280, People's Republic of China
| | - Qiquan Sun
- Department of Renal Transplantation, Lingnan Hospital, The Third Affiliated Hospital, Sun Yat-sen University, Kaichuang Road 2693, Huangpu District, Guangzhou, 510530, People's Republic of China.
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20
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Posttransplant Outcomes of Kidneys Donated After Brain Death Followed by Circulatory Death: A Cohort Study of 128 Chinese Patients. Transplant Direct 2017; 3:e189. [PMID: 28795141 PMCID: PMC5540627 DOI: 10.1097/txd.0000000000000704] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Accepted: 05/31/2017] [Indexed: 11/26/2022] Open
Abstract
Background Donation after brain death followed by circulatory death (DBCD) is a new class in the unique Chinese donor classification system. Currently, in China, the organ transplantation of DBCD is rising. However, there is a dearth of research on the characteristics and outcomes of DBCD kidney transplantation. Method We collected 128 DBCD renal transplant patients who underwent surgery between June 2013 and May 2016 at our center to analyze clinical outcomes and to share our experience to enhance perioperative management in DBCD kidney transplantation. Results At the end of follow-up, no patients experienced primary nonfunction, but delayed graft function occurred in 25.8%. One- and 3-year graft survivals were 97.7% and 94.5%, respectively. The average length of stay was 20.88 ± 14.6 days, the incidence of posttransplant complications was 46.1% (59 patients), and 31 patients suffered more than 1 complication. In addition, the average length of stay of patients without complications and with at least 1 complication was 13.07 ± 2.01 days and 30.02 ± 17.4 days, respectively. There was a significantly higher incidence of complications associated with the postoperative hospital stay in DBCD patients. Conclusions Patients who received a DBCD kidney demonstrated a good outcome in terms of both graft survival and graft function. Hence, DBCD is suitable for national reality and conditions and offers a feasible option for deceased-donor kidney transplantation in China. To prevent complications and reduce the duration of hospital stay, we should strengthen preoperative and postoperative management.
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Sekijima M, Sahara H, Miki K, Villani V, Ariyoshi Y, Iwanaga T, Tomita Y, Yamada K. Hydrogen sulfide prevents renal ischemia-reperfusion injury in CLAWN miniature swine. J Surg Res 2017; 219:165-172. [PMID: 29078877 DOI: 10.1016/j.jss.2017.05.123] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2017] [Revised: 05/17/2017] [Accepted: 05/25/2017] [Indexed: 11/17/2022]
Abstract
BACKGROUND Hydrogen sulfide (H2S) has recently been reported to demonstrate both antiinflammatory and cytoprotective effects; however, its efficacy has not been well documented in large animal models. In this study, we examined whether the administration of H2S offers cytoprotective effects on renal ischemia-reperfusion injury (IRI) in a preclinical miniature swine model. METHODS Major histocompatibility complex-inbred, CLAWN miniature swine (n = 9) underwent a right nephrectomy, followed by induction of a 120-min period of warm ischemia via placement of clamps on the left renal artery and vein. Group 1 (n = 3) underwent renal ischemia without H2S administration. Groups 2 (n = 3) and 3 (n = 3) received Na2S (prodrug of H2S) 10 min before reperfusion of the ischemic kidneys followed by a 30-min of Na2S postreperfusion intravenously (group 2) or selective administration of Na2S via the left renal artery (group 3). IRI was assessed by kidney biopsies, levels of inflammatory cytokines in sera and kidney tissue. RESULTS Animals in group 1 had significantly higher serum creatinine levels compared with animals in groups 2 and 3 (P < 0.01). Histology showed severe tubular damage with TUNEL-positive cells in group 1 on postoperative day 2 compared with mild damage in group 2 and minimal damage in group 3. Furthermore, levels of inflammatory cytokines in both serum (interleukin-6 [IL-6], tumor necrosis factor-α, and high-mobility group box 1) and renal tissue (IL-1 and IL-6) in group 3 were markedly lower than in group 2, suggesting beneficial effects of selective Na2S administration. CONCLUSIONS Na2S administration, especially via an organ selective approach, appears to potentially offer cytoprotective and antiinflammatory effects following renal IRI.
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Affiliation(s)
- Mitsuhiro Sekijima
- Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan
| | - Hisashi Sahara
- Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan
| | - Katsuyuki Miki
- Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan; The 3rd Department of the Surgery, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan
| | - Vincenzo Villani
- Transplantation Biology Research Center Laboratory, Center for Transplantation Sciences, Massachusetts General Hospital, Boston, Massachusetts
| | - Yuichi Ariyoshi
- Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan
| | - Takehiro Iwanaga
- Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan
| | - Yusuke Tomita
- Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan
| | - Kazuhiko Yamada
- Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan.
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22
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Cristelli MP, Cofán F, Tedesco-Silva H, Trullàs JC, Santos DWCL, Manzardo C, Agüero F, Moreno A, Oppenheimer F, Diekmann F, Medina-Pestana JO, Miro JM. Regional differences in the management and outcome of kidney transplantation in patients with human immunodeficiency virus infection: A 3-year retrospective cohort study. Transpl Infect Dis 2017; 19. [PMID: 28508573 DOI: 10.1111/tid.12724] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2016] [Revised: 02/06/2017] [Accepted: 03/05/2017] [Indexed: 12/24/2022]
Abstract
BACKGROUND In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. OBJECTIVES We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. METHODS This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT. RESULTS Between 2005 and 2015, 54 KTs were performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia time was higher in Brazil (25 vs 18 hours, P=.001). Biopsy-proven acute rejection (AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes (22 vs 4, P=.063). Patient survival at 3 years was 91.3% in Brazil and 100% in Spain; P=.663. All three cases of death in Brazil were a result of bacterial infections within the first year post transplant. At 3 years, survival free from immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir-based treatment to avoid interaction with calcineurin inhibitor was more prevalent in Spain (80% vs 3%; P<.001). HIV infection remained under control in all patients, with undetectable viral load and no opportunistic infections. CONCLUSION Important regional differences exist in the demographics and management of immunosuppression and antiretroviral therapy. These details may influence AR and infectious complications. Non-AIDS infections leading to early mortality in Brazil deserve special attention.
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Affiliation(s)
| | - Federico Cofán
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | - Joan Carles Trullàs
- Hospital d'Olot, Medical Science Department, University of Girona, Girona, Spain
| | | | | | - Fernando Agüero
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Asunción Moreno
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | - Fritz Diekmann
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
| | | | - Jose Maria Miro
- Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
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Wagenaar S, Nederhoed JH, Hoksbergen AWJ, Bonjer HJ, Wisselink W, van Ramshorst GH. Minimally Invasive, Laparoscopic, and Robotic-assisted Techniques Versus Open Techniques for Kidney Transplant Recipients: A Systematic Review. Eur Urol 2017; 72:205-217. [PMID: 28262412 DOI: 10.1016/j.eururo.2017.02.020] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2016] [Accepted: 02/09/2017] [Indexed: 12/14/2022]
Abstract
CONTEXT Literature on conventional and minimally invasive operative techniques has not been systematically reviewed for kidney transplant recipients. OBJECTIVE To systematically evaluate, summarize, and review evidence supporting operating technique and postoperative outcome for kidney transplant recipients. EVIDENCE ACQUISITION A systematic review was conducted in PubMed-Medline, Embase, and Cochrane Library between 1966 up to September 1, 2016, according to Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Articles were included and scored by two independent reviewers using Group Reading Assessment and Diagnostic Evaluation (GRADE), Newcastle-Ottawa Quality Assessment Scale (NOS), and Oxford guidelines for level of evidence. Main outcomes were graft survival, surgical site infection, incisional hernia, and cosmetic result. In total, 18 out of 1954 identified publications were included in this analysis. EVIDENCE SYNTHESIS Included reports described conventional open, minimally invasive open, laparoscopic, and robotic-assisted techniques. General level of evidence of included studies was low (GRADE: 1-3; NOS: 0-4; and Oxford level of evidence: 4-2). No differences in graft or patient survival were found. For open techniques, Gibson incision showed better results than the hockey-stick incision for incisional hernia (4% vs 16%), abdominal wall relaxation (8% vs 24%), and cosmesis. Minimally invasive operative recipient techniques showed lowest surgical site infection (range 0-8%) and incisional hernia rates (range 0-6%) with improved cosmetic result and postoperative recovery. Disadvantages included prolonged cold ischemia time, warm ischemia time, and total operation time. CONCLUSIONS Although the level of evidence was generally low, minimally invasive techniques showed promising results with regard to complications and recovery, and could be considered for use. For open surgery, the smallest possible Gibson incision appeared to yield favorable results. PATIENT SUMMARY In this paper, the available evidence for minimally invasive operation techniques for kidney transplantation was reviewed. The quality of the reviewed research was generally low but suggested possible advantages for minimally invasive, laparoscopic, and robot-assisted techniques.
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Affiliation(s)
- Sven Wagenaar
- Department of Surgery, VU Medical Center, Amsterdam, The Netherlands; Department of Urology, Meander Medical Centre, Amersfoort, The Netherlands.
| | | | | | - H Jaap Bonjer
- Department of Surgery, VU Medical Center, Amsterdam, The Netherlands
| | - Willem Wisselink
- Department of Surgery, VU Medical Center, Amsterdam, The Netherlands
| | - Gabrielle H van Ramshorst
- Department of Surgery, VU Medical Center, Amsterdam, The Netherlands; Department of Surgery, Dutch Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
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Ding C, Xue W, Tian P, Ding X, Pan X, Yan H, Xiang H, Feng X, Hou J, Tian X, Li Y, Zheng J. Outcomes of standard dose EC-MPS with low exposure to CsA in DCD renal transplantation recipients with DGF. Int J Clin Pract 2016:8-15. [PMID: 26176940 DOI: 10.1111/ijcp.12661] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
AIMS The lower limit of exposure to cyclosporine A (CsA) has not yet been established in donation after cardiac death (DCD) renal transplantation recipients with delayed graft function (DGF) receiving enteric-coated mycophenolate sodium (EC-MPS) therapy. Stable and adequate mycophenolic acid (MPA) dosing may facilitate lower CsA exposure after DCD renal transplantation in recipients with DGF without compromising safety. METHODS A 12-month, single-centre open-label prospective trial was performed in our centre. According to their DGF risk index using the previous DGF prediction models, we divided up the patients on oral CsA into either a DGF group (n = 26) and no DGF group (n = 48). All of the patients initially received the standard EC-MPS dosing (1440 mg/day). The initial dose of CsA in the low risk of DGF group was 4.5 mg/kg/day and in the high risk of DGF group was 2.5 mg/kg/day. Efficacy parameters, safety and tolerability were assessed over a 12-month study period. RESULTS The incidence of DGF was 18.5% in the 162 DCD recipients. Between the DGF group and the no DGF group, the 1-year patient survival and graft survival were not significantly different. The incidence of BPAR was higher in the DGF group (26.9% vs. 8.3%, p = 0.032). Most patients in the DGF group had recovery of renal function after 1 month. The adverse events between the two groups were not significantly different. The daily EC-MPS doses of the DGF group were significantly higher than the no DGF group before the 6-month follow-up period. There were no significant differences between the two groups regarding the mean AUC levels during the follow-up period. CONCLUSIONS These results show that low expose CsA with standard dosing of EC-MPS and thymoglobulin was efficacious, safe and well-tolerated in DCD renal transplant recipients with DGF in China. Furthermore, stable and adequate MPA exposure helped to reduce the dose of and exposure to CsA. Thus, this may lead to less-induced nephrotoxicity and better renal function recovery.
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Affiliation(s)
- C Ding
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - W Xue
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - P Tian
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - X Ding
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - X Pan
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - H Yan
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - H Xiang
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - X Feng
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - J Hou
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - X Tian
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - Y Li
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
| | - J Zheng
- Department of Renal Transplantation, Nephropathy Hospital, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, China.,Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an, China
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Thuret R, Timsit MO, Kleinclauss F. [Chronic kidney disease and kidney transplantation]. Prog Urol 2016; 26:882-908. [PMID: 27727091 DOI: 10.1016/j.purol.2016.09.051] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 09/01/2016] [Indexed: 01/05/2023]
Abstract
OBJECTIVES To report epidemiology and characteristics of end-stage renal disease (ESRD) patients and renal transplant candidates, and to evaluate access to waiting list and results of renal transplantation. MATERIAL AND METHODS An exhaustive systematic review of the scientific literature was performed in the Medline database (http://www.ncbi.nlm.nih.gov) and Embase (http://www.embase.com) using different associations of the following keywords: "chronic kidney disease, epidemiology, kidney transplantation, cost, survival, graft, brain death, cardiac arrest, access, allocation". French legal documents have been reviewed using the government portal (http://www.legifrance.gouv.fr). Articles were selected according to methods, language of publication and relevance. The reference lists were used to identify additional historical studies of interest. Both prospective and retrospective series, in French and English, as well as review articles and recommendations were selected. In addition, French national transplant and health agencies (http://www.agence-biomedecine.fr and http://www.has-sante.fr) databases were screened using identical keywords. A total of 3234 articles, 6 official reports and 3 newspaper articles were identified; after careful selection 99 publications were eligible for our review. RESULTS The increasing prevalence of chronic kidney disease (CKD) leads to worsen organ shortage. Renal transplantation remains the best treatment option for ESRD, providing recipients with an increased survival and quality of life, at lower costs than other renal replacement therapies. The never-ending lengthening of the waiting list raises issues regarding treatment strategies and candidates' selection, and underlines the limits of organ sharing without additional source of kidneys available for transplantation. CONCLUSION Allocation policies aim to reduce medical or geographical disparities regarding enrollment on a waiting list or access to an allotransplant.
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Affiliation(s)
- R Thuret
- Service d'urologie et transplantation rénale, CHU de Montpellier, 34090 Montpellier, France; Université de Montpellier, 34090 Montpellier, France.
| | - M O Timsit
- Service d'urologie, hôpital européen Georges-Pompidou, AP-HP, 75015 Paris, France; Université Paris Descartes, 75006 Paris, France
| | - F Kleinclauss
- Service d'urologie et transplantation rénale, CHRU de Besançon, 25030 Besançon, France; Université de Franche-Comté, 25030 Besançon, France; Inserm UMR 1098, 25030 Besançon, France
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Domínguez-Gil B, Duranteau J, Mateos A, Núñez JR, Cheisson G, Corral E, De Jongh W, Del Río F, Valero R, Coll E, Thuong M, Akhtar MZ, Matesanz R. Uncontrolled donation after circulatory death: European practices and recommendations for the development and optimization of an effective programme. Transpl Int 2016; 29:842-59. [PMID: 26706366 DOI: 10.1111/tri.12734] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 06/19/2015] [Accepted: 12/16/2015] [Indexed: 12/16/2022]
Abstract
The shortage of organs remains one of the biggest challenges in transplantation. To address this, we are increasingly turning to donation after circulatory death (DCD) donors and now in some countries to uncontrolled DCD donors. We consolidate the knowledge on uncontrolled DCD in Europe and provide recommendations and guidance for the development and optimization of effective uncontrolled DCD programmes.
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Affiliation(s)
| | - Jacques Duranteau
- Department of Anesthesia and Intensive Care, Bicêtre Hospital, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Assistance Publique des Hôpitaux de Paris, Paris, France
| | - Alonso Mateos
- Summa 112 and Francisco de Vitoria University, Madrid, Spain
| | - Jose R Núñez
- Transplant Coordination Unit, Hospital Clínico San Carlos, Madrid, Spain
| | - Gaelle Cheisson
- Department of Anesthesia and Intensive Care, Bicêtre Hospital, Hôpitaux Universitaires Paris-Sud, Université Paris-Sud, Assistance Publique des Hôpitaux de Paris, Paris, France
| | | | - Wim De Jongh
- Transplant Coordination Unit, University Hospital Maastricht, Maastricht, The Netherlands
| | - Francisco Del Río
- Transplant Coordination Unit, Hospital Clínico San Carlos, Madrid, Spain
| | - Ricard Valero
- Department of Anesthesia, Hospital Clínic de Barcelona, Barcelona, Spain
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Fung A, Zhao H, Yang B, Lian Q, Ma D. Ischaemic and inflammatory injury in renal graft from brain death donation: an update review. J Anesth 2016; 30:307-16. [DOI: 10.1007/s00540-015-2120-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Accepted: 12/08/2015] [Indexed: 12/20/2022]
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28
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van Heurn LWE, Talbot D, Nicholson ML, Akhtar MZ, Sanchez-Fructuoso AI, Weekers L, Barrou B. Recommendations for donation after circulatory death kidney transplantation in Europe. Transpl Int 2015; 29:780-9. [PMID: 26340168 DOI: 10.1111/tri.12682] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2015] [Revised: 06/19/2015] [Accepted: 08/26/2015] [Indexed: 12/29/2022]
Abstract
Donation after circulatory death (DCD) donors provides an invaluable source for kidneys for transplantation. Over the last decade, we have observed a substantial increase in the number of DCD kidneys, particularly within Europe. We provide an overview of risk factors associated with DCD kidney function and survival and formulate recommendations from the sixth international conference on organ donation in Paris, for best-practice guidelines. A systematic review of the literature was performed using Ovid Medline, Embase and Cochrane databases. Topics are discussed, including donor selection, organ procurement, organ preservation, recipient selection and transplant management.
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Affiliation(s)
| | - David Talbot
- Department of Liver/Renal Transplant, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Michael L Nicholson
- Department of Surgery, NIHR Cambridge Biomedical Research Centre, Cambridge, UK
| | | | | | - Laurent Weekers
- Department of Nephrology-Dialysis-Transplantation, University of Liège, CHU Sart Tilman, Liège, Belgium
| | - Benoit Barrou
- Department of Urology - Transplantation, GHzu Pitié Salpêtriere, Paris, France
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29
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Miranda-Utrera N, Medina-Polo J, Pamplona-Casamayor M, Passas-Martínez JB, Rodríguez-Antolín A, de la Rosa Kehrmann F, Duarte-Ojeda JM, Tejido-Sánchez A, Villacampa Aubá F, Andrés Belmonte A. Uncontrolled non-heartbeating donors (types i-ii) with normothermic recirculation vs. heartbeating donors: evaluation of functional results and survival. Actas Urol Esp 2015; 39:429-34. [PMID: 25749460 DOI: 10.1016/j.acuro.2015.01.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Revised: 01/26/2015] [Accepted: 01/27/2015] [Indexed: 11/19/2022]
Abstract
OBJECTIVE Non-heartbeating donors (NHBD) are an alternative to heartbeating donors (HBD). Our objective was to compare functional results and kidney survival from NHBDs and HBDs. MATERIAL AND METHODS A retrospective study comparing the results of 236 normothermically preserved kidneys from type i and ii type NHBDs with the results of 250 from HBDs that were transplanted in our center between 2005 and 2012. Homogeneity between groups was tested and we evaluated the presence of delayed graft function (DGF) associated with pretransplant variables of the donor and recipient. RESULTS Both groups show homogeneity in pretransplant characteristics in terms of: age, HLA incompatibilities, and recipient hemodialysis time. Average follow-up time was 33 months (range 0-87) for NHBDs and 38 months (range 0-90) for HBDs. 5.5% of NHBDs showed primary non-function (PNF) vs. 4% of HBDs (P=.42) and 80.9% of DGF vs. 46.8% of HBDs (P<.001). At the end of the follow-up, there were no statistically significant differences in the survival of grafts (92.8% for NHBD vs. 93.6% for HBD, P=.71) and recipients (99.1% NHBD vs. 98.6% HBD, P=.28). CONCLUSIONS Although the DGF percentage was greater for NHBDs, final creatinine as well as graft and recipient survival were similar for both groups. Therefore, in our experience, kidneys from NHBDs have similar results to those from HBDs and are an excellent source of organs for transplantation.
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Affiliation(s)
- N Miranda-Utrera
- Servicio de Urología, Hospital Universitario 12 de Octubre, Madrid, España
| | - J Medina-Polo
- Servicio de Urología, Hospital Universitario 12 de Octubre, Madrid, España.
| | | | | | | | | | - J M Duarte-Ojeda
- Servicio de Urología, Hospital Universitario 12 de Octubre, Madrid, España
| | - A Tejido-Sánchez
- Servicio de Urología, Hospital Universitario 12 de Octubre, Madrid, España
| | - F Villacampa Aubá
- Servicio de Urología, Hospital Universitario 12 de Octubre, Madrid, España
| | - A Andrés Belmonte
- Servicio de Nefrología y Coordinación de Trasplantes, Hospital Universitario 12 de Octubre, Madrid, España
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The effect of prolonged of warm ischaemic injury on renal function in an experimental ex vivo normothermic perfusion system. J Transl Med 2015; 13:207. [PMID: 26123198 PMCID: PMC4486682 DOI: 10.1186/s12967-015-0571-4] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 06/10/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Donation after circulatory death (DCD) kidney transplants inevitably sustain a degree of warm ischaemic injury, which is manifested clinically as delayed graft function. The aim of this study was to define the effects of prolonged periods of warm ischaemic injury on renal function in a normothermic haemoperfused kidney model. METHODS Porcine kidneys were subjected to 15, 60, 90 (n = 6 per group) and 120 min (n = 4) of in situ warm ischaemia (WI) and then retrieved, flushed with cold preservation fluid and stored in ice for 2 h. Kidneys then underwent 3 h of normothermic reperfusion with a whole blood-based perfusate using an ex vivo circuit developed from clinical grade cardiopulmonary bypass technology. RESULTS Creatinine clearance, urine output and fractional excretion of sodium deteriorated sequentially with increasing warm time. Renal function was severely compromised after 90 or 120 min of WI but haemodynamic, metabolic and histological parameters demonstrated the viability of kidneys subjected to prolonged warm ischaemia. CONCLUSIONS Isolated kidney perfusion using a warm, oxygenated, red cell-based perfusate allows an accurate ex vivo assessment of the potential for recovery from warm ischaemic injury. Prolonged renal warm ischaemic injury caused a severe decrement in renal function but was not associated with tissue necrosis.
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31
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Xiaoming P, Xiang H, LinJuan L, Chenguang D, Ren L. Preliminary results of transplantation with kidneys donated after cardiac death: a path of hope for organ transplantation in China. Nephrol Dial Transplant 2015; 30:1590-6. [PMID: 25843782 DOI: 10.1093/ndt/gfv049] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2014] [Accepted: 02/04/2015] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND This article aims to explore the feasibility and effect of kidney transplantation (KT) from donation after cardiac death (DCD) donors in China. METHODS From July 2011 to April 2013, 94 DCD kidneys retrieved and transplanted by our centre were reviewed in this largest single-centre cohort study. Patients with and without delayed graft function (DGF) were compared between DCD KT cohorts. Estimated glomerular filtration rate (eGFR), post-operative complications and graft loss at different time points were recorded. Factors related to DGF were examined and analysed. RESULTS There was no primary non-function (PNF) graft observed from patients. DGF rate was 27.7%; and 1-year overall graft and patient survival rates were 95.7 and 98.9%, respectively. In the first 6 months post-transplantation, eGFR was significantly lower in the DGF group compared with the non-DGF group (46 versus 52 mL/min; P = 0.04); but the difference disappeared thereafter (50 versus 47 mL/min, after 1 year). CONCLUSION Despite early DGF and short-term observations, we are pleased to have this opportunity of sharing our initial experience and results, and justifying the continued DCD KT programmes in China.
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Affiliation(s)
- Pan Xiaoming
- Center of Nephropathy, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an City, Shaanxi Province, People's Republic of China Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an City, Shaanxi Province, People's Republic of China
| | - Heli Xiang
- Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an City, Shaanxi Province, People's Republic of China
| | - Liu LinJuan
- Coordination Group of Shaanxi Red Cross Organization, Xi'an City, Shaanxi Province, People's Republic of China
| | - Ding Chenguang
- Center of Nephropathy, The First Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an City, Shaanxi Province, People's Republic of China
| | - Li Ren
- Institute of Organ Transplantation, Xi'an Jiaotong University, Xi'an City, Shaanxi Province, People's Republic of China
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Chen GD, Lai XQ, Ko DSC, Qiu J, Wang CX, Han M, Li J, Huang G, He XS, Chen LZ. Comparison of efficacy and safety between rabbit anti-thymocyte globulin and anti-T lymphocyte globulin in kidney transplantation from donation after cardiac death: a retrospective cohort study. Nephrology (Carlton) 2015; 20:539-43. [PMID: 25808082 DOI: 10.1111/nep.12469] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2015] [Indexed: 12/01/2022]
Abstract
AIM To compare the efficacy and safety between rabbit anti-thymocyte globulin (Thymoglobulin) and anti-T lymphocyte globulin (ATG-Fresenius, ATG-F) in donation after cardiac death (DCD) kidney transplantation. METHODS We retrospectively analyzed 255 cases of DCD kidney transplantation performed at our hospital from February 2007 to October 2013. The patients were divided into two groups based on their induction therapies with Thymoglobulin (n = 188) or ATG-F (n = 67). Clinical data were collected and compared between the two groups. RESULTS Delayed graft function (DGF) occurred in 36 (19.1%) patients in the Thymoglobulin group versus 17 (25.4%) patients in the ATG-F group (P = 0.281). However, if we subgroup the patients with increased risk factors for DGF, the DGF rate was 9/40 (22.5%) in the Thymoglobulin group versus 9/16 (56.3%) in the ATG-F group (P = 0.015). Duration of DGF was significantly shorter in the Thymoglobulin group (11.7 days vs. 16.1 days). The acute rejection rate was significantly lower in the Thymoglobulin group (9.6% vs. 19.4%, P = 0.035). One-year graft and patient survival were both comparable between the Thymoglobulin and ATG-F groups. The adjusted odds ratio of DGF was 4.283 (1.137-16.13) between the ATG-F and Thymoglobulin groups in patients with increased risk factors for DGF. CONCLUSION Compared with ATG-F, Thymoglobulin may reduce duration of DGF and acute rejection rate after DCD kidney transplantation. Moreover, Thymoglobulin significantly reduced DGF in patients with increased risk factors for DGF.
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Affiliation(s)
- Guo-Dong Chen
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xing-Qiang Lai
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Dicken Shiu-Chung Ko
- Departments of Urology and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Jiang Qiu
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Chang-Xi Wang
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Ming Han
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Jun Li
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Gang Huang
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Xiao-Shun He
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Li-Zhong Chen
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
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Kidney Allograft Fibrosis After Transplantation From Uncontrolled Circulatory Death Donors. Transplantation 2015; 99:409-15. [DOI: 10.1097/tp.0000000000000228] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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A comparison of inflammatory, cytoprotective and injury gene expression profiles in kidneys from brain death and cardiac death donors. Transplantation 2014; 98:15-21. [PMID: 24901651 DOI: 10.1097/tp.0000000000000136] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND The superior long-term survival of kidneys from living donors (LDs) compared with kidneys from donation-after-brain-death (DBD) and donation-after-cardiac-death (DCD) donors is now well established. However, comparative studies on transcriptional changes that occur at organ retrieval and during and after cold ischemia (CI) are sparse. METHODS Using a rat model, we used qRT-PCR to examine expression levels of inflammatory, cytoprotective, and injury genes at different time points after organ retrieval. Cleaved caspase-3 was used to evaluate early apoptosis in DCD and DBD kidneys. RESULTS Immediately after retrieval, we found massive up-regulation of proinflammatory genes interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, P-selectin, and E-selectin in DBD compared with LD and DCD kidneys. A significant increase in the expression of injury markers Kim-1, p21, and the cytoprotective gene heme oxygenase-1 accompanied this. Bax was increased in DCD kidneys, and Bcl-2 was decreased in DBD kidneys. After 2 hr of CI in the LD group and 18 hr in the DBD and DCD groups, gene expression levels were similar to those found after retrieval. During 18 hr of cold storage, expression levels of these genes did not change. In DCD and DBD kidneys, early apoptosis increased after CI. DISCUSSION/CONCLUSION The gene expression profile in DBD kidneys represents an inflammatory and injury response to brain death. In contrast, DCD kidneys show only mild up-regulation of inflammatory and injury genes. These results may imply why delayed graft function in DCD kidneys does not have the deleterious effect it has on DBD kidneys.
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Allain G, Kerforne T, Thuret R, Delpech PO, Saint-Yves T, Pinsard M, Hauet T, Giraud S, Jayle C, Barrou B. Development of a preclinical model of donation after circulatory determination of death for translational application. Transplant Res 2014; 3:13. [PMID: 24999383 PMCID: PMC4082279 DOI: 10.1186/2047-1440-3-13] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Accepted: 06/04/2014] [Indexed: 11/23/2022] Open
Abstract
Background Extracorporeal membranous oxygenation is proposed for abdominal organ procurement from donation after circulatory determination of death (DCD). In France, the national Agency of Biomedicine supervises the procurement of kidneys from DCD, specifying the durations of tolerated warm and cold ischemia. However, no study has determined the optimal conditions of this technique. The aim of this work was to develop a preclinical model of DCD using abdominal normothermic oxygenated recirculation (ANOR). In short, our objectives are to characterize the mechanisms involved during ANOR and its impact on abdominal organs. Methods We used Large White pigs weighing between 45 and 55 kg. After 30 minutes of potassium-induced cardiac arrest, the descending thoracic aorta was clamped and ANOR set up between the inferior vena cava and the abdominal aorta for 4 hours. Hemodynamic, respiratory and biochemical parameters were collected. Blood gasometry and biochemistry analysis were performed during the ANOR procedure. Results Six ANOR procedures were performed. The surgical procedure is described and intraoperative parameters and biological data are presented. Pump flow rates were between 2.5 and 3 l/min. Hemodynamic, respiratory, and biochemical objectives were achieved under reproducible conditions. Interestingly, animals remained hemodynamically stable following the targeted protocol. Arterial pH was controlled, and natremia and renal function remained stable 4 hours after the procedure was started. Decreased hemoglobin and serum proteins levels, concomitant with increased lactate dehydrogenase activity, were observed as a consequence of the surgery. The serum potassium level was increased, owing to the extracorporeal circulation circuit. Conclusions Our ANOR model is the closest to clinical conditions reported in the literature and will allow the study of the systemic and abdominal organ impact of this technique. The translational relevance of the pig will permit the determination of new biomarkers and protocols to improve DCD donor management.
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Affiliation(s)
- Géraldine Allain
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service de Chirurgie cardio-thoracique, Poitiers F-86000, France
| | - Thomas Kerforne
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service de Réanimation chirurgicale, Poitiers F-86000, France
| | - Rodolphe Thuret
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Montpellier, Service d'Urologie et de transplantation rénale, Montpellier F-34295, France
| | - Pierre-Olivier Delpech
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service d'Urologie, Poitiers F-86000, France
| | - Thibaut Saint-Yves
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service d'Urologie, Poitiers F-86000, France
| | - Michel Pinsard
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service de Réanimation chirurgicale, Poitiers F-86000, France ; CHU de Montpellier, Service d'Urologie et de transplantation rénale, Montpellier F-34295, France
| | - Thierry Hauet
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers F-86000, France ; CHU Poitiers, Service de Biochimie, Poitiers F-86000, France ; IBISA Platform 'Experimental Surgery and Transplantation', INRA, Domaine expérimental du Magneraud, Surgères F-17700, France
| | - Sébastien Giraud
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU Poitiers, Service de Biochimie, Poitiers F-86000, France
| | - Christophe Jayle
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; CHU de Poitiers, Service de Chirurgie cardio-thoracique, Poitiers F-86000, France ; Université de Poitiers, Faculté de Médecine et de Pharmacie, Poitiers F-86000, France ; IBISA Platform 'Experimental Surgery and Transplantation', INRA, Domaine expérimental du Magneraud, Surgères F-17700, France
| | - Benoît Barrou
- INSERM U1082, CHU de Poitiers, rue de la Milétrie, B.P. 577, F-86021 Cedex Poitiers, France ; GH Pitié-Salpêtrière, AP-HP, Service d'Urologie et de transplantation rénale, Paris F-75013, France ; UPMC Université Paris VI, Paris F-75013, France
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36
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Benaragama SK, Tymkewycz T, John BJ, Davenport A, Lindsey B, Nicol D, Olsburgh J, Drage M, Mamode N, Calder F, Taylor J, Koffman G, Kessaris N, Morsy M, Cacciola R, Puliatti C, Fernadez-Diaz S, Syed A, Hakim N, Papalois V, Fernando BS. Do we need a different organ allocation system for kidney transplants using donors after circulatory death? BMC Nephrol 2014; 15:83. [PMID: 24885114 PMCID: PMC4035739 DOI: 10.1186/1471-2369-15-83] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2013] [Accepted: 05/19/2014] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND There is no national policy for allocation of kidneys from Donation after circulatory death (DCD) donors in the UK. Allocation is geographical and based on individual/regional centre policies. We have evaluated the short term outcomes of paired kidneys from DCD donors subject to this allocation policy. METHODS Retrospective analysis of paired renal transplants from DCD's from 2002 to 2010 in London. Cold ischemia time (CIT), recipient risk factors, delayed graft function (DGF), 3 and 12 month creatinine) were compared. RESULTS Complete data was available on 129 paired kidneys.115 pairs were transplanted in the same centre and 14 pairs transplanted in different centres. There was a significant increase in CIT in kidneys transplanted second when both kidneys were accepted by the same centre (15.5 ± 4.1 vs 20.5 ± 5.8 hrs p<0.0001 and at different centres (15.8 ± 5.3 vs. 25.2 ± 5.5 hrs p=0.0008). DGF rates were increased in the second implant following sequential transplantation (p=0.05). CONCLUSIONS Paired study sequential transplantation of kidneys from DCD donors results in a significant increase in CIT for the second kidney, with an increased risk of DGF. Sequential transplantation from a DCD donor should be avoided either by the availability of resources to undertake simultaneous procedures or the allocation of kidneys to 2 separate centres.
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Affiliation(s)
- Shanka K Benaragama
- UCL Centre for Nephrology, Royal Free hospital, London, UK
- Centre for Nephrology and Transplantation, Royal Free London NHS Trust, Pond Street, London NW3 2QG, UK
| | | | - Biku J John
- UCL Centre for Nephrology, Royal Free hospital, London, UK
| | | | - Ben Lindsey
- UCL Centre for Nephrology, Royal Free hospital, London, UK
| | - David Nicol
- UCL Centre for Nephrology, Royal Free hospital, London, UK
| | - Jonathon Olsburgh
- Department of Renal Transplantation, Guys and St. Thomas’ Hospital, London, UK
| | - Martin Drage
- Department of Renal Transplantation, Guys and St. Thomas’ Hospital, London, UK
| | - Nizam Mamode
- Department of Renal Transplantation, Guys and St. Thomas’ Hospital, London, UK
| | - Francis Calder
- Department of Renal Transplantation, Guys and St. Thomas’ Hospital, London, UK
| | - John Taylor
- Department of Renal Transplantation, Guys and St. Thomas’ Hospital, London, UK
| | - Geoff Koffman
- Department of Renal Transplantation, Guys and St. Thomas’ Hospital, London, UK
| | - Nicos Kessaris
- Department of Renal Transplantation, Guys and St. Thomas’ Hospital, London, UK
| | - Mohamed Morsy
- Department of Renal Transplantation, St George’s Hospital, London, UK
| | - Roberto Cacciola
- Department of Renal Transplantation, Royal London & St Bart’s NHS Trust, London, UK
| | - Carmelo Puliatti
- Department of Renal Transplantation, Royal London & St Bart’s NHS Trust, London, UK
| | - Susana Fernadez-Diaz
- Department of Renal Transplantation, Royal London & St Bart’s NHS Trust, London, UK
| | - Asim Syed
- West London Renal Transplant Centre, Hammersmith Hospital, London, UK
| | - Nadey Hakim
- West London Renal Transplant Centre, Hammersmith Hospital, London, UK
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37
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van Rijt WG, Secher N, Keller AK, Møldrup U, Chynau Y, Ploeg RJ, van Goor H, Nørregaard R, Birn H, Frøkiaer J, Nielsen S, Leuvenink HGD, Jespersen B. α-Melanocyte stimulating hormone treatment in pigs does not improve early graft function in kidney transplants from brain dead donors. PLoS One 2014; 9:e94609. [PMID: 24728087 PMCID: PMC3984270 DOI: 10.1371/journal.pone.0094609] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Accepted: 03/17/2014] [Indexed: 01/24/2023] Open
Abstract
Delayed graft function and primary non-function are serious complications following transplantation of kidneys derived from deceased brain dead (DBD) donors. α-melanocyte stimulating hormone (α-MSH) is a pleiotropic neuropeptide and its renoprotective effects have been demonstrated in models of acute kidney injury. We hypothesized that α-MSH treatment of the recipient improves early graft function and reduces inflammation following DBD kidney transplantation. Eight Danish landrace pigs served as DBD donors. After four hours of brain death both kidneys were removed and stored for 18 hours at 4°C in Custodiol preservation solution. Sixteen recipients were randomized in a paired design into two treatment groups, transplanted simultaneously. α-MSH or a vehicle was administered at start of surgery, during reperfusion and two hours post-reperfusion. The recipients were observed for ten hours following reperfusion. Blood, urine and kidney tissue samples were collected during and at the end of follow-up. α-MSH treatment reduced urine flow and impaired recovery of glomerular filtration rate (GFR) compared to controls. After each dose of α-MSH, a trend towards reduced mean arterial blood pressure and increased heart rate was observed. α-MSH did not affect expression of inflammatory markers. Surprisingly, α-MSH impaired recovery of renal function in the first ten hours following DBD kidney transplantation possibly due to hemodynamic changes. Thus, in a porcine experimental model α-MSH did not reduce renal inflammation and did not improve short-term graft function following DBD kidney transplantation.
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Affiliation(s)
- Willem G. van Rijt
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
- Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands
- * E-mail:
| | - Niels Secher
- Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark
| | - Anna K. Keller
- Department of Urology, Aarhus University Hospital, Aarhus, Denmark
| | - Ulla Møldrup
- Department of Urology, Aarhus University Hospital, Aarhus, Denmark
| | - Yahor Chynau
- Department of Urology, Aarhus University Hospital, Aarhus, Denmark
| | - Rutger J. Ploeg
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Harry van Goor
- Department of Pathology and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands
| | - Rikke Nørregaard
- Department of Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark
| | - Henrik Birn
- Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
- The Water and Salt Research Center, Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Jørgen Frøkiaer
- The Water and Salt Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Søren Nielsen
- The Water and Salt Research Center, Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | - Henri G. D. Leuvenink
- Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
| | - Bente Jespersen
- Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark
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38
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Lee G, Barlow A, Doughman T, Nicholson ML. External iliac artery dissection causing early renal transplant dysfunction. BMJ Case Rep 2014; 2014:bcr-2014-204160. [PMID: 24695666 DOI: 10.1136/bcr-2014-204160] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
External iliac artery dissection after kidney transplantation is a rare, catastrophic but potentially reversible complication. Treatment which may save both the transplant and the patient requires clinical suspicion, timely imaging, and prompt intervention. This case report describes successful diagnosis of this complication and surgical intervention which saved the kidney and safeguarded blood supply to the patient's leg.
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Affiliation(s)
- Gwyn Lee
- Department of Infection, Immunity and Inflammation: Transplant Group, University of Leicester, Leicester, UK
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39
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Antoine C, Mourey F, Prada-Bordenave E. How France launched its donation after cardiac death program. ACTA ACUST UNITED AC 2014; 33:138-43. [DOI: 10.1016/j.annfar.2013.11.018] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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40
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Shapey IM, Muiesan P. Regional perfusion by extracorporeal membrane oxygenation of abdominal organs from donors after circulatory death: a systematic review. Liver Transpl 2013; 19:1292-303. [PMID: 24136827 DOI: 10.1002/lt.23771] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2013] [Accepted: 09/10/2013] [Indexed: 12/25/2022]
Abstract
Organs from donors after circulatory death (DCDs) are particularly susceptible to the effects of warm ischemia injury. Regional perfusion (RP) by extracorporeal membrane oxygenation (ECMO) is increasingly being advocated as a useful remedy to the effects of ischemia/reperfusion injury, and it has been reported to enable the transplantation of organs from donors previously deemed unsuitable. The MEDLINE, Embase, and Cochrane databases were searched, and articles published between 1997 and 2013 were obtained. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Two hundred ten articles were identified, and 11 were eligible for inclusion. Four hundred eighty-two kidneys and 79 livers were transplanted from regional perfusion-supported donor after circulatory death (RP-DCD) sources. One-year graft survival was lower with uncontrolled RP-DCD liver transplantation, whereas 1-year patient survival was similar. Primary nonfunction and ischemic cholangiopathy were significantly more frequent with RP-DCDs versus donors after brain death (DBDs), but there was no difference in postoperative mortality between the 2 groups. The 1-year patient and graft survival rates for RP-DCD kidney transplantation were better than the rates with standard DCDs and were comparable to, if not better than, the rates with DBDs. At experienced centers, delayed graft function (DGF) for kidney transplantation from RP-DCDs was much less frequent in comparison with all other donor types. In conclusion, RP aids the recovery of DCD organs from ischemic injury and enables transplantation with acceptable survival. RP may help to increase the donor pool, but its benefits must still be balanced with the recognition of significantly higher rates of complications in liver transplantation. In kidney transplantation, significant reductions in DGF can be obtained with RP, and there are potentially important implications for long-term outcomes. Significant ethicolegal issues exist, and they are preventing a worldwide consensus on optimum RP protocols and an accurate appreciation of outcomes.
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Affiliation(s)
- Iestyn M Shapey
- Department of Transplantation Surgery, Manchester Royal Infirmary, Manchester, United Kingdom
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41
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Lebranchu Y, Baan C, Biancone L, Legendre C, Morales JM, Naesens M, Thomusch O, Friend P. Pretransplant identification of acute rejection risk following kidney transplantation. Transpl Int 2013; 27:129-38. [DOI: 10.1111/tri.12205] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 08/26/2013] [Accepted: 10/02/2013] [Indexed: 02/05/2023]
Affiliation(s)
- Yvon Lebranchu
- Department of Nephrology and Clinical Immunology EA 4245 CHRU Tours Tours France
| | - Carla Baan
- Department of Internal Medicine Erasmus MC University Medical Centre Rotterdam The Netherlands
| | - Luigi Biancone
- Division of Nephrology, Dialysis and Transplantation Department of Medical Sciences Molinette Hospital University of Turin Turin Italy
| | | | | | - Maarten Naesens
- Department of Nephrology, Dialysis and Renal Transplantation University Hospitals Leuven Leuven Belgium
| | - Oliver Thomusch
- Department of General Surgery University Clinic of Freiburg Freiburg Germany
| | - Peter Friend
- Nuffield Department of Surgical Sciences Oxford Transplant Centre Oxford UK
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42
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Comparison of Kidney Function Between Donation After Cardiac Death and Donation After Brain Death Kidney Transplantation. Transplantation 2013; 96:274-81. [DOI: 10.1097/tp.0b013e31829807d1] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
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43
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Outcome of Renal Transplantation From Deceased Donors After Cardiac Death: A Single-Center Experience From a Developing Country. Transplant Proc 2013; 45:2147-51. [PMID: 23953524 DOI: 10.1016/j.transproceed.2013.02.128] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2012] [Revised: 12/18/2012] [Accepted: 02/05/2013] [Indexed: 01/14/2023]
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44
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Antithymocyte globulin induction and rapid steroid taper leads to excellent results in kidney transplantation with donation after cardiac death donors: importance of rejection and delayed graft function. Transplant Proc 2013; 45:1528-30. [PMID: 23726612 DOI: 10.1016/j.transproceed.2013.01.050] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Accepted: 01/03/2013] [Indexed: 11/24/2022]
Abstract
Recipients of primary transplants from donation after cardiac death (DCD) donors (n = 40) performed from January 2005 to December 2009 were retrospectively reviewed and compared with recipients of primary transplants from donation after brain death (DBD) donors (n = 142). Patients received rabbit antithymocyte globulin induction and rapid steroid taper (RST; steroids stopped 5 days after surgery). Maintenance immunosuppression included tacrolimus and mycophenolate mofetil. Protocol kidney biopsies, creatinine (Cr), and measured glomerular filtration rate (mGFR; determined by cold iothalamate or 24-h creatinine clearance) were obtained at 1, 4, 12, and 24 months. Kidney biopsies for cause were conducted for unexplained elevated Cr, decline in mGFR, or new proteinuria. Biopsies were graded for rejection according to the Banff criteria. Graft survival at 3 years was 90.0% for DCD recipients and 86.6% for DBD recipients (P = NS). Rejection of any grade diagnosed on any biopsy through the first 2 years occurred in 18 DCD (45%) and 50 DBD (35%) recipients. Rejection of a grade more than Banff borderline occurred in 12.5% DCD and 12.7% DBD recipients. At 2 years, the mean ± SEM Cr and mGFR for DCD recipients with rejection were 1.8 ± 0.29 mg/dL and 59.2 ± 8.5 mL/min versus 1.3 ± 0.11 mg/dL and 67.0 ± 7.8 ml/min for those without rejection. For DBD recipients with rejection, Cr and mGFR at 2 years were 1.7 ± 0.12 mg/dL and 54.0 ± 4.4 mL/min versus 1.4 ± 0.11 mg/dL and 66.6 ± 3.3 ml/min for those without rejection (P = NS). Comparing DCD to DBD, there was no statistical difference in mean Cr or mGFR outcomes. Regardless of group, grafts with delayed graft function had lower 3-year survival. DCD primary kidney transplant recipients treated with rabbit antithymocyte induction and RST have short-term graft survival and function equivalent to DBD recipients. RST appears to be acceptable immunosuppression for DCD recipients.
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45
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Chen GD, Shiu-Chung Ko D, Wang CX, Qiu J, Han M, He XS, Chen LZ. Kidney transplantation from donors after cardiac death: an initial report of 71 cases from China. Am J Transplant 2013; 13:1323-6. [PMID: 23464380 DOI: 10.1111/ajt.12190] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2012] [Revised: 12/28/2012] [Accepted: 12/29/2012] [Indexed: 01/25/2023]
Abstract
Shortage of deceased donors is a severe problem in recent years in China especially in a culture in which brain death criteria is not widely accepted. Donation after cardiac death (DCD) has been reported to expand the donor pool despite higher rates of primary nonfunction (PNF) and delayed graft function (DGF) after transplantation. We collected 71 DCD kidney transplants performed at our hospital between February, 2007 and June, 2012 with aims to demonstrate the feasibility of DCD donation in China. All patients were followed up, and postoperative complications and graft loss were recorded. The PNF rate was 2.8%, and DGF rate was 28.2%. The 1- and 3-year graft survival was 95.7% and 92.4%. In conclusion, graft survival of DCD kidney transplantation in China is excellent despite of higher rates of PNF and DGF after transplantation.
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Affiliation(s)
- G-D Chen
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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46
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Hoogland ERP, de Vries EE, Christiaans MHL, Winkens B, Snoeijs MGJ, van Heurn LWE. The value of machine perfusion biomarker concentration in DCD kidney transplantations. Transplantation 2013; 95:603-10. [PMID: 23296150 DOI: 10.1097/tp.0b013e31827908e6] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Donation after cardiac death (DCD) increases the number of donor kidneys but is associated with more primary nonfunction (PNF) and delayed graft function (DGF). It has been suggested that biomarkers in the preservation solution of machine perfused kidneys may predict PNF, although evidence is lacking. METHODS We analyzed the diagnostic accuracy of the perfusate biomarkers glutathione S-transferase, lactate dehydrogenase (LDH), heart-type fatty acid binding protein, redox-active iron, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin to predict PNF and DGF in 335 DCD kidneys preserved by hypothermic machine perfusion at our center between 1 January 1997 and 1 January 2008. The diagnostic accuracy of these biomarkers to predict PNF was evaluated with the area under the receiver operating characteristics curves. Additionally, the risk of DGF and graft failure was assessed. RESULTS LDH and IL-18 concentrations were associated with PNF (odds ratio [95% confidence interval], 1.001 [1.000-1.002]; P=0.005 and 1.001 [1.000-1.002]; P=0.003, respectively) in a multivariate analysis; the diagnostic accuracy for PNF was "poor" for all biomarkers but increased to "fair" for redox-active iron and IL-18 in a multivariate analysis (area under the receiver operating characteristics curves, 0.701 and 0.700, respectively). LDH and IL-18 concentrations were associated with DGF; biomarker concentration was not associated with 1-year graft survival. CONCLUSIONS The diagnostic accuracy of the perfusate biomarkers glutathione S-transferase, LDH, heart-type fatty acid binding protein, redox-active iron, IL-18, and neutrophil gelatinase-associated lipocalin to predict viability of DCD kidneys varies from "poor" to "fair". Therefore, DCD kidneys should not be discarded because of high biomarker perfusate concentration.
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Affiliation(s)
- E R Pieter Hoogland
- Department of Surgery, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
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47
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Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death. Transplantation 2013; 94:1218-23. [PMID: 23154212 DOI: 10.1097/tp.0b013e3182708e30] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. METHODS We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. RESULTS Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and 82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD recipients, the 1-year graft survival rate was worse in the presence of DGF (88% vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88% vs. 96%, P=0.04). CONCLUSION Despite the high incidence of DGF, medium-term outcomes of DCD kidney transplants are comparable to those from DBD transplants. Short-term graft survival from DCD transplants is not adversely influenced by DGF and AR, unlike in DBD transplants.
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48
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Pieter Hoogland ER, van Smaalen TC, Christiaans MHL, van Heurn LWE. Kidneys from uncontrolled donors after cardiac death: which kidneys do worse? Transpl Int 2013; 26:477-84. [DOI: 10.1111/tri.12067] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2012] [Revised: 12/23/2012] [Accepted: 01/06/2013] [Indexed: 12/31/2022]
Affiliation(s)
- E. R. Pieter Hoogland
- Department of Surgery; Maastricht University Medical Center; Maastricht; The Netherlands
| | - Tim C. van Smaalen
- Department of Surgery; Maastricht University Medical Center; Maastricht; The Netherlands
| | | | - L. W. Ernest van Heurn
- Department of Surgery; Maastricht University Medical Center; Maastricht; The Netherlands
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49
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Snyder RA, Moore DR, Moore DE. More donors or more delayed graft function? A cost-effectiveness analysis of DCD kidney transplantation. Clin Transplant 2013; 27:289-96. [PMID: 23350938 DOI: 10.1111/ctr.12073] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/11/2012] [Indexed: 02/04/2023]
Abstract
Expansion of the donor pool with expanded criteria donors and donation after cardiac death (DCD) donors is essential. DCD grafts result in increased rates of primary non-function (PNF) and delayed graft function (DGF). However, long-term patient and graft survival is similar between donation after brain death (DBD) donors and DCD donors. The aim of this study was to evaluate the cost-effectiveness of the use of DCD donors. A Markov-based decision analytic model was created to simulate outcomes for two wait list strategies: (i) wait list composed of only DBD organs and (ii) wait list combining DBD and DCD organs. Baseline values and ranges were determined from the Scientific Registry of Transplant Recipients (SRTR) database and literature review. Sensitivity analyses were conducted to test model strength and parameter variability. The wait list strategy consisting of DBD donors only provided recipients 5.4 Quality-adjusted life years (QALYs) at $65 000/QALY, whereas a wait list strategy combining DBD + DCD donors provided recipients 6.0 QALYs at a cost of $56 000/QALY. Wait lists with DCD donors provide adequate long-term survival despite more DGF. This equates to an improvement in quality of life and decreased cost when compared to remaining on dialysis for any period of time.
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Affiliation(s)
- Rebecca A Snyder
- Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN, USA
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Miranda-Utrera N, Medina-Polo J, Pamplona M, de la Rosa F, Rodríguez A, Duarte JM, Passas JB, Mateos-Rodríguez A, Díaz R, Andrés A. Donation after cardiac death: results of the SUMMA 112 - Hospital 12 de Octubre Program. Clin Transplant 2013; 27:283-8. [DOI: 10.1111/ctr.12071] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2012] [Indexed: 11/29/2022]
Affiliation(s)
| | - José Medina-Polo
- Department of Urology; Hospital Universitario 12 de Octubre; Madrid; Spain
| | - Manuel Pamplona
- Department of Urology; Hospital Universitario 12 de Octubre; Madrid; Spain
| | | | - Alfredo Rodríguez
- Department of Urology; Hospital Universitario 12 de Octubre; Madrid; Spain
| | - José M. Duarte
- Department of Urology; Hospital Universitario 12 de Octubre; Madrid; Spain
| | - Juan B. Passas
- Department of Urology; Hospital Universitario 12 de Octubre; Madrid; Spain
| | | | - Rafael Díaz
- Department of Urology; Hospital Universitario 12 de Octubre; Madrid; Spain
| | - Amado Andrés
- Department ofDepartment of Nephrology; Hospital Universitario 12 de Octubre; Madrid; Spain
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