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Mahler CF, Friedl F, Nusshag C, Speer C, Benning L, Göth D, Schaier M, Sommerer C, Mieth M, Mehrabi A, Michalski C, Renders L, Bachmann Q, Heemann U, Krautter M, Schwenger V, Echterdiek F, Zeier M, Morath C, Kälble F. Evaluation of deceased-donor kidney offers: development and validation of novel data driven and expert based prediction models for early transplant outcomes. Front Immunol 2025; 15:1511368. [PMID: 39840033 PMCID: PMC11747414 DOI: 10.3389/fimmu.2024.1511368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2024] [Accepted: 12/06/2024] [Indexed: 01/23/2025] Open
Abstract
In the face of growing transplant waitlists and aging donors, sound pre-transplant evaluation of organ offers is paramount. However, many transplant centres lack clear criteria on organ acceptance. Often, previous scores for donor characterisation have not been validated for the Eurotransplant population and are not established to support graft acceptance decisions. Here, we investigated 1353 kidney transplantations at three different German centres to develop and validate novel statistical models for the prediction of early adverse graft outcome (EAO), defined as graft loss or CKD ≥4 within three months. The predictive models use generalised estimating equations (GEE) accounting for potential correlations between paired grafts from the same donor. Discriminative accuracy and calibration were determined via internal and external validation in the development (935 recipients, 309 events) and validation cohort (418 recipients, 162 events) respectively. The expert model is based on predictor ratings by senior transplant nephrologists, while for the data-driven model variables were selected via high-dimensional lasso generalised estimating equations (LassoGee). Both models show moderate discrimination for EAO (C-statistic expert model: 0,699, data-driven model 0,698) with good calibration. In summary, we developed novel statistical models that represent current clinical consensus and are tailored to the older deceased donor population. Compared to KDRI, our described models are sparse with only four and three predictors respectively and account for paired grafts from the same donor, while maintaining a discriminative accuracy equal or better than the established KDRI-score.
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Affiliation(s)
- Christoph F. Mahler
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Felix Friedl
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christian Nusshag
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Claudius Speer
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Louise Benning
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Daniel Göth
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Matthias Schaier
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Claudia Sommerer
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Christoph Michalski
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Lutz Renders
- Department of Nephrology, Klinikum Rechts der Isar, Technische Universität München (TUM), Munich, Germany
| | - Quirin Bachmann
- Department of Nephrology, Klinikum Rechts der Isar, Technische Universität München (TUM), Munich, Germany
| | - Uwe Heemann
- Department of Nephrology, Klinikum Rechts der Isar, Technische Universität München (TUM), Munich, Germany
| | - Markus Krautter
- Department of Nephrology, Hospital Stuttgart, Stuttgart, Germany
| | - Vedat Schwenger
- Department of Nephrology, Hospital Stuttgart, Stuttgart, Germany
| | - Fabian Echterdiek
- Department of Nephrology, Klinikum Rechts der Isar, Technische Universität München (TUM), Munich, Germany
- Department of Nephrology, Hospital Stuttgart, Stuttgart, Germany
| | - Martin Zeier
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Christian Morath
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
| | - Florian Kälble
- Department of Nephrology, University Hospital Heidelberg, Heidelberg, Germany
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Baryła M, Skrzycki M, Danielewicz R, Kosieradzki M, Struga M. Protein biomarkers in assessing kidney quality before transplantation‑current status and future perspectives (Review). Int J Mol Med 2024; 54:107. [PMID: 39370783 PMCID: PMC11448562 DOI: 10.3892/ijmm.2024.5431] [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: 04/05/2024] [Accepted: 07/31/2024] [Indexed: 10/08/2024] Open
Abstract
To meet the demand for kidney transplants (KTx), organs are frequently retrieved not only from standard criteria donors (SCD; a donor who is aged <50 years and suffered brain death from any number of causes, such as traumatic injuries or a stroke) but also from expanded criteria donors (any donor aged >60 years or donors aged >50 years with two of the following: A history of high blood pressure, a creatinine serum level ≥1.5 mg/dl or death resulting from a stroke). This comes at the cost of a higher risk of primary non‑function (the permanent hyperkalemia, hyperuremia and fluid overload that result in the need for continuous dialysis after KTx), delayed graft function (the need for dialysis session at least once during the first week after KTx), earlier graft loss and urinary complications (vesico‑ureteral reflux, obstruction of the vesico‑ureteral anastomosis, urine leakage). At present, there are no commercially available diagnostic tools for assessing kidney quality prior to KTx. Currently available predictive models based on clinical data, such as the Kidney Donor Profile Index, are insufficient. One promising option is the application of perfusion solutions for protein biomarkers of kidney quality and predictors of short‑ and long‑term outcomes. However, to date, protein markers that can be detected with ELISA, western blotting and cytotoxic assays have not been identified to be a beneficial predictors of kidney quality. These include lactate dehydrogenases, glutathione S‑transferases, fatty acid binding proteins, extracellular histones, IL‑18, neutrophil gelatinase‑associated lipocalin, MMPs and kidney injury molecule‑1. However, novel methods, including liquid chromatography‑mass spectrometry (LC‑MS) and microarrays, allow the analysis of all renal proteins suspended/dissolved in the acellular preservation solution used for kidney storage before KTx (including hypothermic machine perfusion as one of kidney storage methods) e.g. Belzer University of Wisconsin. Recent proteomic studies utilizing LC‑MS have identified complement pathway elements (C3, C1QB, C4BPA, C1S, C1R and C1RL), desmoplakin, blood coagulation pathway elements and immunoglobulin heavy variable 2‑26 to be novel predictors of kidney quality before transplantation. This was because they were found to correlate with estimated glomerular filtration rate at 3 and 12 months after kidney transplantation. However, further proteomic studies focusing on distinct markers obtained from hypothermic and normothermic machine perfusion are needed to confirm their predictive value and to improve kidney storage methods. Therefore, the present literature review from PubMed, Scopus, Embase and Web of Science was performed with the aims of summarizing the current knowledge on the most frequently studied single protein biomarkers. In addition, novel analytical methods and insights into organ injury during preservation were documented, where future directions in assessing organ quality before kidney transplantation were also discussed.
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Affiliation(s)
- Maksymilian Baryła
- Chair and Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland
- Department of General and Transplant Surgery, Infant Jesus Hospital, Medical University of Warsaw, 02-006 Warsaw, Poland
| | - Michał Skrzycki
- Chair and Department of Biochemistry, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Roman Danielewicz
- Department of General and Transplant Surgery, Infant Jesus Hospital, Medical University of Warsaw, 02-006 Warsaw, Poland
| | - Maciej Kosieradzki
- Department of General and Transplant Surgery, Infant Jesus Hospital, Medical University of Warsaw, 02-006 Warsaw, Poland
| | - Marta Struga
- Department of General and Transplant Surgery, Infant Jesus Hospital, Medical University of Warsaw, 02-006 Warsaw, Poland
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Gomes VM, Dos Santos LI, de Carvalho Silva BDP, Fabreti-Oliveira RA. Impact of donor expanded criteria kidney transplantation on clinical outcomes and survival: A single-center experience. Transpl Immunol 2024; 86:102116. [PMID: 39233095 DOI: 10.1016/j.trim.2024.102116] [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: 03/21/2024] [Revised: 08/20/2024] [Accepted: 09/01/2024] [Indexed: 09/06/2024]
Abstract
INTRODUCTION The scarcity of suitable donor organs has led to the inclusion of Expanded Criteria Donor (ECD) kidneys to augment the donor pool, despite potential concerns regarding post-transplant outcomes. METHODS This retrospective study analyzed the clinical outcomes of a cohort of 317 kidney transplant recipients from deceased donors at a single center between 2008 and 2018. Patients were categorized into ECD and Standard Criteria Donor (SCD) groups, with primary nonfunctioning grafts excluded. Comprehensive laboratory evaluations were conducted, including HLA typing and serum creatinine levels. Immunosuppressive regimens were standardized, and statistical analyses were performed using the SPSS program. RESULTS The sample consisted of 83 (26.18%) patients who received kidney transplants from ECDs and 234 (73.82%) from SCDs. The ECD group showed a longer cold ischemia time (p = 0.019) and a higher rate of delayed graft function (DGF) compared with the SCD group. No significant differences were observed in graft survival (p = 0.370) or patient survival (p = 0.993) between the ECD and SCD groups. However, differences in graft survival were noted between the groups when stratified by DGF status: ECD with DGF vs. ECD without DGF (p = 0.029), ECD with DGF vs. SCD with DGF (p = 0.188), ECD with DGF vs. SCD without DGF (p = 0.022), ECD without DGF vs. SCD with DGF (p = 0.014), ECD without DGF vs. SCD without DGF (p = 0.340), and SCD with DGF vs. SCD without DGF (p = 0.195). No differences in patient survival rates were observed among these groups for all pairwise comparisons (p > 0.05) when stratified by donor criteria and DGF status. CONCLUSIONS Graft and patient survival rates were comparable between ECD and SCD kidney transplant recipients.
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Affiliation(s)
| | | | | | - Raquel A Fabreti-Oliveira
- Faculty of Medical Sciences, Belo Horizonte, Minas Gerais State, Brazil; IMUNOLAB - Laboratory of Histocompatibility, Belo Horizonte, Minas Gerais State, Brazil.
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Tedesco Silva H, Ramos TRDM, de Carvalho DDBM, Ferreira GF, de Andrade JMM, de Andrade LGM, Abbud-Filho M, Foresto RD, Manfro RC, Esmeraldo RDM, Freitas TVDS, Garcia VD, Pestana JM, Fonseca MCM. Use of Machine Perfusion to Increase the Number of Expanded Criteria Deceased Donor Kidney Transplants: A Pharmacoeconomic Analysis. Transplant Direct 2024; 10:e1668. [PMID: 38988688 PMCID: PMC11230806 DOI: 10.1097/txd.0000000000001668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 04/10/2024] [Indexed: 07/12/2024] Open
Abstract
Background The discard of expanded criteria donor (ECD) kidneys is unacceptably high, considering the growing demand for transplantation. Using machine perfusion may reduce the discard rate, increase the number of transplants, and reduce mortality on the waiting list. Methods We developed a 5-y Markov model to simulate incorporating the pulsatile perfusion machine into the current government-funded healthcare system. The model compared the universal use of static cold storage for all kidneys with the selective use of machine perfusion for ECD kidneys. Real-life data were used to compose the cohort characteristics in this model. This pharmacoeconomic analysis aimed to determine the cost-effectiveness and budgetary impact of using machine perfusion to preserve ECD kidneys. Results Compared with the universal use of static cold storage, the use of machine perfusion for ECD kidneys was associated with an increase in the number of kidney transplants (n = 1123), a decrease in the number of patients on the waiting list (n = 815), and decrease in mortality (n = 120), with a cost difference of US dollar 4 486 009 in the period. The budget impact analysis revealed an additional cost of US dollar 4 453 749 >5 y. The budget impact analysis demonstrated a progressive reduction in costs, becoming cost-saving during the last year of the analysis. Conclusions This stochastic model showed that incorporating machine perfusion for ECD kidneys is most often a dominant or cost-effective technology associated with an increase in the number of transplants and a reduction in the number of patients on the waiting list, reducing mortality on the waiting list.
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Affiliation(s)
- Helio Tedesco Silva
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Disciplina de Nefrologia, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil
| | - Teresa Raquel de Moraes Ramos
- Women's Health Technology Assessment Center, Department of Gynecology, Federal University of São Paulo, Medical School, São Paulo, Brazil
- Axia.Bio Life Sciences, São Paulo, Brazil
- Axia.Bio Life Sciences, Miami, FL
| | | | | | | | | | - Mario Abbud-Filho
- Hospital de Base, Medical School FAMERP, São José do Rio Preto, Brazil
| | | | | | | | | | | | - José Medina Pestana
- Hospital do Rim, Fundação Oswaldo Ramos, São Paulo, Brazil
- Disciplina de Nefrologia, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil
| | - Marcelo Cunio Machado Fonseca
- Women's Health Technology Assessment Center, Department of Gynecology, Federal University of São Paulo, Medical School, São Paulo, Brazil
- Axia.Bio Life Sciences, São Paulo, Brazil
- Axia.Bio Life Sciences, Miami, FL
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Mella A, Calvetti R, Barreca A, Congiu G, Biancone L. Kidney transplants from elderly donors: what we have learned 20 years after the Crystal City consensus criteria meeting. J Nephrol 2024; 37:1449-1461. [PMID: 38446386 PMCID: PMC11473582 DOI: 10.1007/s40620-024-01888-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 01/03/2024] [Indexed: 03/07/2024]
Abstract
Based on the current projection of the general population and the combined increase in end-stage kidney disease with age, the number of elderly donors and recipients is increasing, raising crucial questions about how to minimize the discard rate of organs from elderly donors and improve graft and patient outcomes. In 2002, extended criteria donors were the focus of a meeting in Crystal City (VA, USA), with a goal of maximizing the use of organs from deceased donors. Since then, extended criteria donors have progressively contributed to a large number of transplanted grafts worldwide, posing specific issues for allocation systems, recipient management, and therapeutic approaches. This review analyzes what we have learned in the last 20 years about extended criteria donor utilization, the promising innovations in immunosuppressive management, and the molecular pathways involved in the aging process, which constitute potential targets for novel therapies.
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Affiliation(s)
- Alberto Mella
- Renal Transplant Center" A. Vercellone," Nephrology, Dialysis, and Renal Transplant Division, "Città Della Salute e Della Scienza" Hospital, Department of Medical Sciences, University of Turin, Corso Bramante, 88, 10126, Turin, Italy
| | - Ruggero Calvetti
- Renal Transplant Center" A. Vercellone," Nephrology, Dialysis, and Renal Transplant Division, "Città Della Salute e Della Scienza" Hospital, Department of Medical Sciences, University of Turin, Corso Bramante, 88, 10126, Turin, Italy
| | - Antonella Barreca
- Division of Pathology, "Città Della Salute e Della Scienza" Hospital, Department of Medical Sciences, University of Turin, Turin, Italy
| | - Giovanni Congiu
- Renal Transplant Center" A. Vercellone," Nephrology, Dialysis, and Renal Transplant Division, "Città Della Salute e Della Scienza" Hospital, Department of Medical Sciences, University of Turin, Corso Bramante, 88, 10126, Turin, Italy
| | - Luigi Biancone
- Renal Transplant Center" A. Vercellone," Nephrology, Dialysis, and Renal Transplant Division, "Città Della Salute e Della Scienza" Hospital, Department of Medical Sciences, University of Turin, Corso Bramante, 88, 10126, Turin, Italy.
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Panisset V, Girerd N, Bozec E, Lamiral Z, d'Hervé Q, Frimat L, Huttin O, Girerd S. Long-term changes in cardiac remodelling in prevalent kidney graft recipients. Int J Cardiol 2024; 403:131852. [PMID: 38360102 DOI: 10.1016/j.ijcard.2024.131852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Revised: 01/26/2024] [Accepted: 02/10/2024] [Indexed: 02/17/2024]
Abstract
BACKGROUND Approximately 15% of kidney transplant (KT) recipients develop de novo heart failure after KT. There are scarce data reporting the long-term changes in cardiac structure and function among KT recipients. Despite the improvement in renal function, transplant-related complications as well as immunosuppressive therapy could have an impact on cardiac remodelling during follow-up. We aimed to describe the long-term changes in echocardiographic parameters in prevalent KT recipients and identify the clinical and laboratory factors associated with these changes. METHODS A centralised blinded review of two echocardiographic examinations after KT (on average after 17 and 39 months post-KT respectively) was performed among 80 patients (age 50.4 ± 16.2, diabetes 13.8% pre-KT), followed by linear regression to identify clinico-biological factors related to echocardiographic changes. RESULTS Left atrial volume index (LAVI) increased significantly (34.2 ± 10.8 mL/m2vs. 37.6 ± 15.0 mL/m2, annualised delta 3.1 ± 11.4 mL/m2/year; p = 0.034) while left ventricular ejection fraction (LVEF) decreased (62.1 ± 9.0% vs. 59.7 ± 9.9%, annualised delta -2.7 ± 13.6%/year; p = 0.04). Male sex (β = 8.112 ± 2.747; p < 0.01), pre-KT hypertension (β = 9.725 ± 4.156; p < 0.05), graft from expanded criteria donor (β = 3.791 ± 3.587; p < 0.05), and induction by anti-thymocyte globulin (β = 7.920 ± 2.974; p = 0.01) were associated with an increase in LAVI during follow-up. Higher haemoglobin (>12.9 g/dL) at the time of the first echocardiography (β = 6.029 ± 2.967; p < 0.05) and ACEi/ARB therapy (β = 8.306 ± 3.161; p < 0.05) were associated with an increase in LVEF during follow-up. CONCLUSION This study confirms the existence of long-term cardiac remodelling after KT despite dialysis cessation, characterised by an increase in LAVI and a decrease in LVEF. A better management of anaemia and using ACEi/ARB therapy may prevent such remodelling.
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Affiliation(s)
- Valentin Panisset
- Nephrology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - Nicolas Girerd
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm U1116; CHRU Nancy; F-CRIN INI-CRCT, Vandoeuvre-lès-Nancy, France
| | - Erwan Bozec
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm U1116; CHRU Nancy; F-CRIN INI-CRCT, Vandoeuvre-lès-Nancy, France
| | - Zohra Lamiral
- Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm U1116; CHRU Nancy; F-CRIN INI-CRCT, Vandoeuvre-lès-Nancy, France
| | - Quentin d'Hervé
- Nephrology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - Luc Frimat
- Nephrology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France
| | - Olivier Huttin
- Cardiology Department, University Hospital of Nancy, Vandoeuvre-lès- Nancy, France
| | - Sophie Girerd
- Nephrology Department, University Hospital of Nancy, Vandoeuvre-lès-Nancy, France; Université de Lorraine, Inserm, Centre d'Investigations Cliniques-1433, and Inserm U1116; CHRU Nancy; F-CRIN INI-CRCT, Vandoeuvre-lès-Nancy, France.
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Ergisi M, Ooi B, Salim O, Papalois V. Post-transplant lymphoproliferative disorders following kidney transplantation: A literature review with updates on risk factors, prognostic indices, screening strategies, treatment and analysis of donor type. Transplant Rev (Orlando) 2024; 38:100837. [PMID: 38430887 DOI: 10.1016/j.trre.2024.100837] [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: 07/19/2023] [Revised: 01/31/2024] [Accepted: 02/19/2024] [Indexed: 03/05/2024]
Abstract
Post-transplant lymphoproliferative disorders (PTLD) is a devastating complication of kidney transplantation with an insidious presentation and potential to disseminate aggressively. This review delineates the risk factors, prognostic indexes, screening, current management algorithm and promising treatment strategies for PTLD. Kidneys from both extended criteria donors (ECD) and living donors (LD) are being increasingly used to expand the donor pool. This review also delineates whether PTLD outcomes vary based on these donor sources. While Epstein-Barr virus (EBV) is a well-known risk factor for PTLD development, the use of T-cell depleting induction agents has been increasingly implicated in aggressive, monomorphic forms of PTLD. Research regarding maintenance therapy is sparse. The international prognostic index seems to be the most validate prognostic tool. Screening for PTLD is controversial, as annual PET-CT is most sensitive but costly, while targeted monitoring of EBV-seronegative patients was more economically feasible, is recommended by the American Society of Transplantation, but is limited to a subset of the population. Other screening strategies such as using Immunoglobulin/T-cell receptor require further validation. A risk-stratified approach is taken in the treatment of PTLD. The first step is the reduction of immunosuppressants, after which rituximab and chemotherapy may be introduced if unsuccessful. Some novel treatments have also shown potential benefit in studies: brentuximab vedotin, chimeric antigen receptor T-cell therapy and EBV-specific cytotoxic T lymphocytes. Analysis of LD v DD recipients show no significant difference in incidence and mortality of PTLD but did reveal a shortened time to development of PTLD from transplant. Analysis of SCD vs ECD recipients show a higher incidence of PTLD in the ECD group, which might be attributed to longer time on dialysis for these patients, age, and the pro-inflammatory nature of these organs. However, incidence of PTLD overall is still extremely low. Efforts should be focused on optimising recipients instead. Minimising the use of T-cell depleting therapy while encouraging research on the effect of new immunosuppressants on PTLD, screening for EBV status are essential, while enabling shared decision-making during counselling when choosing kidney donor types and individualised risk tailoring are strongly advocated.
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Affiliation(s)
- Mehmet Ergisi
- Norfolk and Norwich University Hospital, Norfolk and Norwich University Hospitals NHS Foundation Trust, Department of Medicine, Norwich, United Kingdom.
| | - Bryan Ooi
- Department of Medicine, Imperial College London, London, United Kingdom.
| | - Omar Salim
- Isle of Wight NHS Trust, Parkhurst Road, Newport, United Kingdom
| | - Vassilios Papalois
- Hammersmith Hospital, Imperial College Healthcare NHS Trust, Department of Transplant and General Surgery, London, United Kingdom.
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He W, Xu Y, Gong C, Liu X, Wu Y, Xie X, Chen J, Yu Y, Guo Z, Sun Q. Contrast-enhanced ultrasonography-based renal blood perfusion in brain-dead donors predicts early graft function. Ultrasonography 2023; 42:532-543. [PMID: 37722724 PMCID: PMC10555683 DOI: 10.14366/usg.23006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 04/18/2023] [Accepted: 04/19/2023] [Indexed: 09/20/2023] Open
Abstract
PURPOSE The aim of this study was to quantify renal microcirculatory perfusion in braindead donors using contrast-enhanced ultrasonography (CEUS), and to establish an accurate, noninvasive, and convenient index for predicting delayed graft function (DGF) post-transplantation. METHODS In total, 90 brain-dead donor kidneys (training group, n=60; validation group, n=30) examined between August 2020 and November 2022 were recruited in this prospective study. CEUS was performed on the kidneys of brain-dead donors 24 hours before organ procurement and time-intensity curves were constructed. The main measures were arrival time, time to peak, and peak intensity of the kidney segmental arteries, cortex, and medulla. Recipients were divided into DGF and non-DGF groups according to early post-transplant graft function. The area under the receiver operating characteristic curve (AUC) was used to assess diagnostic performance. RESULTS The arrival time of the kidney segmental artery and cortex and the time interval between the time to peak of the segmental artery and cortex were identified as independent factors associated with DGF by multivariate stepwise regression analysis. A new index for the joint prediction model of three variables, the contrast-enhanced ultrasonography/Kidney Donor Profile index (CEUS-KDPI), was developed. CEUS-KDPI showed high accuracy for predicting DGF (training group: AUC, 0.91; sensitivity, 90.5%; specificity, 92.3%; validation group: AUC, 0.84; sensitivity, 75.0%; specificity, 92.3%). CONCLUSION CEUS-KDPI accurately predicted DGF after kidney transplantation. CEUS may be a potential noninvasive tool for bedside examinations before organ procurement and may be used to predict early renal function after kidney transplants kidneys from donors after brain death.
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Affiliation(s)
- Weiming He
- Organ Transplant Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, China
| | - Yuguang Xu
- Ultrasound Imaging Department, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, China
| | - Chaoyang Gong
- Organ Transplant Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, China
| | - Xiaozhen Liu
- Ultrasound Imaging Department, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, China
| | - Yuqiang Wu
- Organ Transplant Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, China
| | - Xi Xie
- Organ Transplant Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, China
| | - Jiazhen Chen
- Organ Transplant Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, China
| | - Yi Yu
- Organ Transplant Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, China
| | - Zhiyong Guo
- Organ Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Qiang Sun
- Organ Transplant Center, Zhongshan Hospital of Sun Yat-sen University, Zhongshan City People's Hospital, Zhongshan, China
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Patel K, Brotherton A, Chaudhry D, Evison F, Nieto T, Dabare D, Sharif A. All Expanded Criteria Donor Kidneys are Equal But are Some More Equal Than Others? A Population-Cohort Analysis of UK Transplant Registry Data. Transpl Int 2023; 36:11421. [PMID: 37727380 PMCID: PMC10505656 DOI: 10.3389/ti.2023.11421] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 07/31/2023] [Indexed: 09/21/2023]
Abstract
Survival outcomes for kidney transplant candidates based on expanded criteria donor (ECD) kidney type is unknown. A retrospective cohort study was undertaken of prospectively collected registry data of all waitlisted kidney failure patients receiving dialysis in the United Kingdom. All patients listed for their first kidney-alone transplant between 2000-2019 were included. Treatment types included; living donor; standard criteria donor (SCD); ECD60 (deceased donor aged ≥60 years); ECD50-59 (deceased donor aged 50-59 years with two from the following three; hypertension; raised creatinine and/or death from stroke) or remains on dialysis. The primary outcome was all-cause mortality, with time-to-death from listing analyzed using time-dependent non-proportional Cox regression models. The study cohort comprised 47,917 waitlisted kidney failure patients, of whom 34,558 (72.1%) received kidney transplantation. ECD kidneys (n = 7,356) were stratified as ECD60 (n = 7,009) or ECD50-59 (n = 347). Compared to SCD, both ECD60 (Hazard Ratio 1.126, 95% CI 1.093-1.161) and ECD50-59 (Hazard Ratio 1.228, 95% CI 1.113-1.356) kidney recipients have higher all-cause mortality. However, compared to dialysis, both ECD60 (Hazard Ratio 0.194, 95% CI 0.187-0.201) and ECD50-59 (Hazard Ratio 0.218, 95% CI 0.197-0.241) kidney recipients have lower all-cause mortality. ECD kidneys, regardless of definition, provide equivalent and superior survival benefits in comparison to remaining waitlisted.
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Affiliation(s)
- Kamlesh Patel
- Department of Nephrology and Transplantation, University Hospitals Birmingham, Birmingham, United Kingdom
| | - Anna Brotherton
- Department of Nephrology and Transplantation, University Hospitals Birmingham, Birmingham, United Kingdom
| | - Daoud Chaudhry
- School of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Felicity Evison
- Data Science Team, Research Development and Innovation, University Hospitals Birmingham, Birmingham, United Kingdom
| | - Thomas Nieto
- Department of Nephrology and Transplantation, University Hospitals Birmingham, Birmingham, United Kingdom
| | - Dilan Dabare
- Department of Nephrology and Transplantation, University Hospitals Birmingham, Birmingham, United Kingdom
| | - Adnan Sharif
- Department of Nephrology and Transplantation, University Hospitals Birmingham, Birmingham, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
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10
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Axelrod R, Nevo D. A sensitivity analysis approach for the causal hazard ratio in randomized and observational studies. Biometrics 2023; 79:2743-2756. [PMID: 36385393 DOI: 10.1111/biom.13797] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 10/18/2022] [Indexed: 09/13/2023]
Abstract
The hazard ratio (HR) is often reported as the main causal effect when studying survival data. Despite its popularity, the HR suffers from an unclear causal interpretation. As already pointed out in the literature, there is a built-in selection bias in the HR, because similarly to the truncation by death problem, the HR conditions on post-treatment survival. A recently proposed alternative, inspired by the Survivor Average Causal Effect, is the causal HR, defined as the ratio between hazards across treatment groups among the study participants that would have survived regardless of their treatment assignment. We discuss the challenge in identifying the causal HR and present a sensitivity analysis identification approach in randomized controlled trials utilizing a working frailty model. We further extend our framework to adjust for potential confounders using inverse probability of treatment weighting. We present a Cox-based and a flexible non-parametric kernel-based estimation under right censoring. We study the finite-sample properties of the proposed estimation methods through simulations. We illustrate the utility of our framework using two real-data examples.
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Affiliation(s)
- Rachel Axelrod
- Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel
| | - Daniel Nevo
- Department of Statistics and Operations Research, Tel Aviv University, Tel Aviv, Israel
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11
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Ribeiro LC, Almeida M, Malheiro J, Silva F, Nunes-Carneiro D, Martins LS, Pedroso S, Silva-Ramos M. Association of the Calcification Score of the Abdominal Aorta, Common Iliac, and Renal Arteries with Outcomes in Living Kidney Donors. J Clin Med 2023; 12:jcm12093339. [PMID: 37176779 PMCID: PMC10179313 DOI: 10.3390/jcm12093339] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Revised: 05/03/2023] [Accepted: 05/06/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Vascular calcification is an ever-more-common finding in protocoled pre-transplant imaging in living kidney donors. We intended to explore whether a connection could be found between the Agatston calcification score, prior to kidney donation, and post-donation renal function. METHODS This is a retrospective analysis of 156 living kidney donors who underwent living donor nephrectomy between January 2010 and December 2016. We quantified the total calcification score (TCaScore) by calculating the Agatston score for each vessel, abdominal aorta, common iliac, and renal arteries. Donors were placed into two different groups based on their TCaScore: <100 TCaScore group and ≥100 TCaScore group. The relationship between TCaScore, 1-year eGFR, proteinuria, and risk of 1 measurement of decreased renal function (eGFR < 60 mL/min/1.73 m2) over 5 years of follow-up was investigated. RESULTS The ≥100 TCaScore group consisted of 29 (19%) donors, with a median (interquartile range) calcification score of 164 (117-358). This group was significantly older, 56.7 ± 6.9 vs. 45.5 ± 10.6 (p < 0.001), had a higher average BMI (p < 0.019), and had a lower preoperative eGFR (p < 0.014). The 1-year eGFR was similarly diminished, 69.9 ± 15.7 vs. 76.3 ± 15.5 (p < 0.048), while also having an increased risk of decreased renal function during the follow-up, 22% vs. 48% (p < 0.007). CONCLUSIONS Our study, through univariate analyses, found a relationship between a TCaScore > 100, lower 1-year eGFR, and decreased renal function in 5 years. However, a higher-than-expected vascular calcification should not be an excluding factor in donors, although they may require closer monitoring during follow-up.
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Affiliation(s)
- Luís Costa Ribeiro
- School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
| | - Manuela Almeida
- Nephrology and Kidney Transplantation Department, Centro Hospitalar e Universitário do Porto, 4050-366 Porto, Portugal
- Unit for Multidisciplinary Research in Biomedicine, School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
| | - Jorge Malheiro
- Nephrology and Kidney Transplantation Department, Centro Hospitalar e Universitário do Porto, 4050-366 Porto, Portugal
- Unit for Multidisciplinary Research in Biomedicine, School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal
| | - Filipa Silva
- Nephrology and Kidney Transplantation Department, Centro Hospitalar e Universitário do Porto, 4050-366 Porto, Portugal
| | - Diogo Nunes-Carneiro
- Urology Department, Centro Hospitalar e Universitário do Porto, 4050-366 Porto, Portugal
| | - La Salete Martins
- Nephrology and Kidney Transplantation Department, Centro Hospitalar e Universitário do Porto, 4050-366 Porto, Portugal
| | - Sofia Pedroso
- Nephrology and Kidney Transplantation Department, Centro Hospitalar e Universitário do Porto, 4050-366 Porto, Portugal
| | - Miguel Silva-Ramos
- Urology Department, Centro Hospitalar e Universitário do Porto, 4050-366 Porto, Portugal
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12
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Darema M, Athanasopoulou D, Bellos I, Tsoumbou I, Vittoraki AG, Bokos J, Marinaki S, Boletis IN. Evaluation of Kidney Donor Risk Index/Kidney Donor Profile Index as Predictor Tools of Deceased-Donor Kidney Transplant Outcomes in a Greek Cohort. J Clin Med 2023; 12:jcm12062439. [PMID: 36983440 PMCID: PMC10054426 DOI: 10.3390/jcm12062439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 03/16/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
The Kidney Donor Risk Index (KDRI) and Kidney Donor Profile Index (KDPI) have been developed to assess deceased-donor graft quality, although validation of their utility outside the USA remains limited. This single-center retrospective cohort study evaluated the ability of KDRI and KDPI to predict transplant outcomes in a Greek cohort. The efficacy of KDRI, KDPI, and donor's age in predicting death-censored graft failure was primarily assessed. Overall, 394 donors and 456 recipients were included. Death-censored graft survival was significantly worse with increasing KDRI (hazard ratio-HR: 2.21, 95% confidence intervals-CI: 1.16-4.22), KDPI (HR: 1.01, 95% CI: 1.00-1.02), and donor's age (HR: 1.03, 95% CI: 1.00-1.05). The unadjusted discriminative ability was similar for KDPI (C-statistic: 0.54) and donor's age (C-statistic: 0.52). The KDPI threshold of 85 was not predictive of graft failure (p-value: 0.19). Higher KDPI was linked to delayed graft function and worse kidney function, but not among expanded-criteria donor transplantations. No significant association was found between KDRI, KDPI, and patient survival. In conclusion, increasing KDRI and KDPI are linked to worse graft function, although their ability to discriminate long-term graft failure remains limited.
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Affiliation(s)
- Maria Darema
- Department of Nephrology and Kidney Transplantation, Medical School, Laiko General Hospital of Athens, National and Kapodistrian University, 11527 Athens, Greece
| | - Diamanto Athanasopoulou
- Department of Nephrology and Kidney Transplantation, Medical School, Laiko General Hospital of Athens, National and Kapodistrian University, 11527 Athens, Greece
| | - Ioannis Bellos
- Department of Nephrology and Kidney Transplantation, Medical School, Laiko General Hospital of Athens, National and Kapodistrian University, 11527 Athens, Greece
| | - Ioanna Tsoumbou
- Department of Nephrology and Kidney Transplantation, Medical School, Laiko General Hospital of Athens, National and Kapodistrian University, 11527 Athens, Greece
| | - Angeliki G Vittoraki
- Immunology Department & National Tissue Typing Center, General Hospital of Athens "G. Gennimatas", 11527 Athens, Greece
| | - John Bokos
- Transplantation Unit, Laiko General Hospital, 11527 Athens, Greece
| | - Smaragdi Marinaki
- Department of Nephrology and Kidney Transplantation, Medical School, Laiko General Hospital of Athens, National and Kapodistrian University, 11527 Athens, Greece
| | - Ioannis N Boletis
- Department of Nephrology and Kidney Transplantation, Medical School, Laiko General Hospital of Athens, National and Kapodistrian University, 11527 Athens, Greece
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13
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Kidney transplantation from elderly donors (> 70 years): a systematic review. World J Urol 2023; 41:695-707. [PMID: 36907943 DOI: 10.1007/s00345-023-04311-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Accepted: 01/22/2023] [Indexed: 03/14/2023] Open
Abstract
PURPOSE The incidence of kidney transplants from elderly donors over 70 years of age has increased significantly over the past 10 years to reach 20% of available kidney graft in some European countries. However, there is little data available on the outcomes of transplants from these donors. We performed a systematic review to evaluate the outcomes of transplantation from donors over 70 years of age. METHODS A systematic review was performed according to preferred reporting items for systematic reviews and meta-analyses. Medline, Embase, and Cochrane databases were searched to identify all studies reporting outcomes on kidney transplants from donors over 70 years. Due to the heterogeneity of the studies, a meta-analysis could not be performed. RESULTS A total of 29,765 patients in 27 studies were included. The mean donors age was 74.79 years, and proportion of kidney graft from women was 53.54%. The estimated 1- and 5-year kidney death-censored graft survivals from donors > 70 years old were, respectively, 85.95 and 80.27%, and the patient survivals were 90.88 and 71.29%. The occurrence of delayed graft function was 41.75%, and primary non-function was 4.67%. Estimated graft function at 1 and 5 years was 36 and 38 mL/min/1.73 m2. Paucity data were available on post-operative complications. CONCLUSIONS Elderly donors appear to be a reliable source of grafts. However, these transplants are associated with a high rate of delayed graft function without repercussion on long-term graft survival. Allocation strategy to elderly recipients is the main factor of decreased recipient survival.
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14
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Felder S, Fischer P, Böhler K, Angermair S, Treskatsch S, Witte W. [Anaesthesiological management of postmortem organ donors - What Evidence is Out There?]. Anasthesiol Intensivmed Notfallmed Schmerzther 2023; 58:183-193. [PMID: 36958314 DOI: 10.1055/a-1839-5014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/25/2023]
Abstract
The transplantation of organs from postmortem organ donors has been a lifesaving and quality-of-life-improving therapy for patients with irreversible organ failure for many years. In Germany, however, there has been an imbalance between the number of organs donated postmortem and the number of patients on the waiting list for years. The anesthesiological management of multiple organ harvesting (MOE) in postmortem organ donors is not an everyday challenge for various reasons: A lack of practical expertise due to the small number of MOE, even at university hospitals (usually < 20 per year), complex pathophysiological changes in the cardiovascular system and other organ functions of the postmortem organ donor and the lack of guidelines complicate anesthesiological management. This paper compiles the existing literature and reviews whether evidence-based recommendations can be derived for anesthesiologic management for MOE.
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15
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Ashiku L, Dagli C. Identify Hard-to-Place Kidneys for Early Engagement in Accelerated Placement With a Deep Learning Optimization Approach. Transplant Proc 2023; 55:38-48. [PMID: 36641350 DOI: 10.1016/j.transproceed.2022.12.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 12/07/2022] [Indexed: 01/13/2023]
Abstract
Recommended practices that follow match-run sequences for hard-to-place kidneys succumb to many declines, accruing cold ischemic time and exacerbating kidney quality that may lead to unnecessary kidney discard. Hard-to-place deceased donor kidneys accepted and transplanted later in the match-run sequence may threaten higher graft failure rates. Accelerated placement is a practice for organ procurement organizations (OPOs) to allocate high-risk kidneys out of sequence and reach patients at aggressive transplant centers. The current practice of assessing hard-to-place kidneys and engaging in accelerated kidney placements relies heavily on the kidney donor profile index (KDPI) and the number of declines. Although this practice is reasonable, it also accrues cold ischemic time and increases the risk for kidney discard. We use a deep learning optimization approach to quickly identify kidneys at risk for discard. This approach uses Organ Procurement and Transplantation Network data to model kidney disposition. We filter discards and develop a model to predict transplant and discard of recovered and not transplanted kidneys. Kidneys with a higher probability of discard are deemed hard-to-place kidneys, which require early engagement for accelerated placement. Our approach will aid in identifying hard-to-place kidneys before or after procurement and support OPOs to deviate from the match-run for accelerated placement. Compared with the KDPI-only prediction of the kidney disposition, our approach demonstrates a 10% increase in correctly predicting kidneys at risk for discard. Future work will include developing models to identify candidates with an increased benefit from using hard-to-place kidneys.
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Affiliation(s)
- Lirim Ashiku
- Missouri University of Science and Technology, Rolla, MO.
| | - Cihan Dagli
- Missouri University of Science and Technology, Rolla, MO
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16
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Farshbafnadi M, Razi S, Rezaei N. Transplantation. Clin Immunol 2023. [DOI: 10.1016/b978-0-12-818006-8.00008-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
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17
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Kuo FC, Wu TH, Loong CC, Lin NC, Ou SM, Chen CY. The strategy of diminishing age gap effect on different donor-recipient combinations in living donor kidney transplantation. J Chin Med Assoc 2023; 86:65-71. [PMID: 36279143 DOI: 10.1097/jcma.0000000000000822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND The disparity between kidney donation and the number of uremic patients on the waiting list has increased the demand for older live-donor kidneys (OLK). However, the donor-recipient age gap may have an impact on the recipient's outcome. METHODS Patients who underwent living donor kidney transplantation at our institute between 2005 and 2019 were enrolled and categorized into four donor-recipient groups according to age (≥50 years and <50 years). The Estimated Post-Transplant Survival (EPTS) score was used to quantify the recipient's condition. Adjusted models analyzed recipient outcomes and related risks among the four groups. RESULTS Of the 154 pairs of live donors and recipients, OLK did not influence overall or death-censored graft survival. The four donor-recipient combinations had similar recipient outcomes, except it slightly worsened in the "old donor to young recipient" group. The EPTS score (adjusted HR, 1.02; 95% CI, 1.01-1.04; p = 0.014) and rejection (adjusted HR, 4.26; 95% CI, 1.36-13.37; p = 0.013) were significant risk factors for overall and death-censored graft survival, respectively. Recipients with pretransplant diabetes or prior solid organ transplantation could have amplified risk effects. The main causes of graft loss were death in older recipients and chronic rejection in younger recipients. CONCLUSION OLK is safe for young recipients. Nevertheless, adequate immunosuppression should be maintained to prevent rejection and subsequent graft loss, especially for those receiving second kidney transplantation. In contrast, older recipients should avoid overt immunosuppression and control their comorbidities, such as diabetes-related complications to improve their long-term outcomes.
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Affiliation(s)
- Fang-Cheng Kuo
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Tsai-Hun Wu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Che-Chuan Loong
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Niang-Cheng Lin
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Shuo-Ming Ou
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Nephrology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Cheng-Yen Chen
- Division of Transplantation Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
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18
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Taber-Hight E, Paramesh A, Neidlinger N, Lebovitz DJ, Souter M, Taber T. The Impact of Organ Procurement Injury on Transplant Organ Availability. Transplant Proc 2022; 54:2075-2081. [DOI: 10.1016/j.transproceed.2022.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 05/10/2022] [Accepted: 06/16/2022] [Indexed: 11/09/2022]
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19
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Gerken ALH, Keese M, Weiss C, Krücken HS, Pecher KAP, Ministro A, Rahbari NN, Reissfelder C, Rother U, Yazdani B, Kälsch AI, Krämer BK, Schwenke K. Investigation of Different Methods of Intraoperative Graft Perfusion Assessment during Kidney Transplantation for the Prediction of Delayed Graft Function: A Prospective Pilot Trial. J Pers Med 2022; 12:jpm12101749. [PMID: 36294888 PMCID: PMC9605219 DOI: 10.3390/jpm12101749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/13/2022] [Accepted: 10/17/2022] [Indexed: 11/09/2022] Open
Abstract
Delayed graft function (DGF) after renal transplantation is a relevant clinical problem affecting long-term organ function. The early detection of patients at risk is crucial for postoperative monitoring and treatment algorithms. In this prospective cohort study, allograft perfusion was evaluated intraoperatively in 26 kidney recipients by visual and formal perfusion assessment, duplex sonography, and quantitative microperfusion assessment using O2C spectrometry and ICG fluorescence angiography. The O2C tissue spectrometry device provides a quantitative method of microperfusion assessment that can be employed during kidney transplantation as an easy-to-use and highly sensitive alternative to ICG fluorescence angiography. Intraoperative microvascular flow and velocity in the allograft cortex after reperfusion predicted DGF with a sensitivity of 100% and a specificity of 82%. Threshold values of 57 A.U. for microvascular flow and 13 A.U. for microvascular velocity were identified by an ROC analysis. This study, therefore, confirmed that impairment of microperfusion of the allograft cortex directly after reperfusion was a key indicator for the occurrence of DGF after kidney transplantation. Our results support the combined use of intraoperative duplex sonography, for macrovascular quality control, and quantitative microperfusion assessment, such as O2C spectrometry, for individual risk stratification to guide subsequent postoperative management.
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Affiliation(s)
- Andreas L. H. Gerken
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
- Correspondence: ; Tel.: +49-(0)621-383-2225
| | - Michael Keese
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
- European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, D-68167 Mannheim, Germany
| | - Christel Weiss
- Department of Biometry and Statistics, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
| | - Hanna-Sophie Krücken
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
| | - Katarina A. P. Pecher
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
- Lisbon Academic Medical Centre, 1649-035 Lisbon, Portugal
| | - Augusto Ministro
- Lisbon Academic Medical Centre, 1649-035 Lisbon, Portugal
- Vascular Surgery, Heart and Vessels Department, Hospital Santa Maria (CHULN), 1649-035 Lisbon, Portugal
- Faculty of Medicine, University of Lisbon, 1300-477 Lisbon, Portugal
| | - Nuh N. Rahbari
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
| | - Christoph Reissfelder
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
| | - Ulrich Rother
- Department of Vascular Surgery, Friedrich Alexander University Erlangen-Nuremberg, Krankenhausstraße 12, D-91054 Erlangen, Germany
| | - Babak Yazdani
- Department of Medicine V, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
| | - Anna-Isabelle Kälsch
- Department of Medicine V, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
| | - Bernhard K. Krämer
- European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, D-68167 Mannheim, Germany
- Department of Medicine V, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
- Center for Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Straße 13-17, D-68167 Mannheim, Germany
| | - Kay Schwenke
- Department of Surgery, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany
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20
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Ruberto F, Lai Q, Piazzolla M, Brisciani M, Pretagostini R, Garofalo M, Giovanardi F, Nudo F, Poli L, Zullino V, Santopietro P, Rossi M, Berloco PB, Pugliese F. The role of hypothermic machine perfusion in selecting renal grafts with advanced histological score. Artif Organs 2022; 46:1771-1782. [PMID: 35548925 PMCID: PMC9544822 DOI: 10.1111/aor.14308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Revised: 03/21/2022] [Accepted: 04/29/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Few studies explored the role of hypothermic machine perfusion (HMP) in the sub-group of non-standard renal grafts with a biopsy-proven advanced histological impairment. This study aimed to investigate the role of HMP in grafts with a Karpinski Score >3 in terms of the need for dialysis, creatinine reduction ratio at day-7 (CRR7), and 3-year graft survival. METHODS Twenty-three perfused grafts with Karpinski Score >3 evaluated between November 2017 and December 2018 were retrospectively analyzed and compared with a control group of 32 non-perfused grafts transplanted between January 2014 and October 2017. RESULTS After transplantation, perfused grafts had fewer cases requiring dialysis (8.7% vs. 34.4%; p = 0.051), a better reduction in serum creatinine (median at 7 days: 2.2 vs. 4.3 mg/dl; p = 0.045), and shorter length of hospital stay (median 11 vs. 15 days; p = 0.01). Three-year death-censored graft survival was better in the perfused cases (91.3% vs. 77.0%; p = 0.16). In perfused grafts, initial renal resistance (RR) had the best predictive value for renal function recovery after the first week, as defined by CRR7 ≤ 70% (AUC = 0.83; p = 0.02). A cut-off value of 0.5 mm Hg/ml/min showed a sensitivity of 82.4%, a specificity of 83.3%, and diagnostic odds ratio = 23.4. After dividing the entire population into a Low-RR (n = 8) and a High-RR Group (n = 15), more cases with CRR7 ≤ 70% were reported in the latter group (86.7 vs. 13.3%; p = 0.03). CONCLUSION HMP yielded promising results in kidneys with Karpinski Score >3. Initial RR should be of interest in selecting non-standard organs for single kidney transplantation even in impaired histology.
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Affiliation(s)
- Franco Ruberto
- Department of Anesthesiology, Critical Care Medicine and Pain TherapySapienza University of RomeRomeItaly
| | - Quirino Lai
- General Surgery and Organ Transplantation UnitSapienza University of RomeRomeItaly
| | - Mario Piazzolla
- Department of Anesthesiology, Critical Care Medicine and Pain TherapySapienza University of RomeRomeItaly
| | - Matteo Brisciani
- Department of Anesthesiology, Critical Care Medicine and Pain TherapySapienza University of RomeRomeItaly
| | - Renzo Pretagostini
- General Surgery and Organ Transplantation UnitSapienza University of RomeRomeItaly
| | - Manuela Garofalo
- General Surgery and Organ Transplantation UnitSapienza University of RomeRomeItaly
| | - Francesco Giovanardi
- General Surgery and Organ Transplantation UnitSapienza University of RomeRomeItaly
| | - Francesco Nudo
- General Surgery and Organ Transplantation UnitSapienza University of RomeRomeItaly
| | - Luca Poli
- General Surgery and Organ Transplantation UnitSapienza University of RomeRomeItaly
| | - Veronica Zullino
- Department of Anesthesiology, Critical Care Medicine and Pain TherapySapienza University of RomeRomeItaly
| | - Pietro Santopietro
- Department of Anesthesiology, Critical Care Medicine and Pain TherapySapienza University of RomeRomeItaly
| | - Massimo Rossi
- General Surgery and Organ Transplantation UnitSapienza University of RomeRomeItaly
| | - Pasquale B. Berloco
- General Surgery and Organ Transplantation UnitSapienza University of RomeRomeItaly
| | - Francesco Pugliese
- Department of Anesthesiology, Critical Care Medicine and Pain TherapySapienza University of RomeRomeItaly
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21
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Sharif A. Deceased Donor Characteristics and Kidney Transplant Outcomes. Transpl Int 2022; 35:10482. [PMID: 36090778 PMCID: PMC9452640 DOI: 10.3389/ti.2022.10482] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 07/25/2022] [Indexed: 11/25/2022]
Abstract
Kidney transplantation is the therapy of choice for people living with kidney failure who are suitable for surgery. However, the disparity between supply versus demand for organs means many either die or are removed from the waiting-list before receiving a kidney allograft. Reducing unnecessary discard of deceased donor kidneys is important to maximize utilization of a scarce and valuable resource but requires nuanced decision-making. Accepting kidneys from deceased donors with heterogenous characteristics for waitlisted kidney transplant candidates, often in the context of time-pressured decision-making, requires an understanding of the association between donor characteristics and kidney transplant outcomes. Deceased donor clinical factors can impact patient and/or kidney allograft survival but risk-versus-benefit deliberation must be balanced against the morbidity and mortality associated with remaining on the waiting-list. In this article, the association between deceased kidney donor characteristics and post kidney transplant outcomes for the recipient are reviewed. While translating this evidence to individual kidney transplant candidates is a challenge, emerging strategies to improve this process will be discussed. Fundamentally, tools and guidelines to inform decision-making when considering deceased donor kidney offers will be valuable to both professionals and patients.
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Affiliation(s)
- Adnan Sharif
- Department of Nephrology and Transplantation, University Hospitals Birmingham, Queen Elizabeth Hospital, Birmingham, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom
- *Correspondence: Adnan Sharif,
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22
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Bestard O, Thaunat O, Bellini MI, Böhmig GA, Budde K, Claas F, Couzi L, Furian L, Heemann U, Mamode N, Oberbauer R, Pengel L, Schneeberger S, Naesens M. Alloimmune Risk Stratification for Kidney Transplant Rejection. Transpl Int 2022; 35:10138. [PMID: 35669972 PMCID: PMC9163827 DOI: 10.3389/ti.2022.10138] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Accepted: 01/26/2022] [Indexed: 11/13/2022]
Abstract
Different types of kidney transplantations are performed worldwide, including biologically diverse donor/recipient combinations, which entail distinct patient/graft outcomes. Thus, proper immunological and non-immunological risk stratification should be considered, especially for patients included in interventional randomized clinical trials. This paper was prepared by a working group within the European Society for Organ Transplantation, which submitted a Broad Scientific Advice request to the European Medicines Agency (EMA) relating to clinical trial endpoints in kidney transplantation. After collaborative interactions, the EMA sent its final response in December 2020, highlighting the following: 1) transplantations performed between human leukocyte antigen (HLA)-identical donors and recipients carry significantly lower immunological risk than those from HLA-mismatched donors; 2) for the same allogeneic molecular HLA mismatch load, kidney grafts from living donors carry significantly lower immunological risk because they are better preserved and therefore less immunogenic than grafts from deceased donors; 3) single-antigen bead testing is the gold standard to establish the repertoire of serological sensitization and is used to define the presence of a recipient's circulating donor-specific antibodies (HLA-DSA); 4) molecular HLA mismatch analysis should help to further improve organ allocation compatibility and stratify immunological risk for primary alloimmune activation, but without consensus regarding which algorithm and cut-off to use it is difficult to integrate information into clinical practice/study design; 5) further clinical validation of other immune assays, such as those measuring anti-donor cellular memory (T/B cell ELISpot assays) and non-HLA-DSA, is needed; 6) routine clinical tests that reliably measure innate immune alloreactivity are lacking.
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Affiliation(s)
- Oriol Bestard
- Department of Nephrology and Kidney Transplantation, Vall d'Hebrón University Hospital, Barcelona, Spain
| | - Olivier Thaunat
- Department of Transplantation, Nephrology, and Clinical Immunology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France
| | | | - Georg A Böhmig
- Department of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Klemens Budde
- Department of Nephrology and Medical Intensive Care, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Frans Claas
- Eurotransplant Reference Laboratory, Department of Immunology, Leiden University Medical Center, Leiden, Netherlands
| | - Lionel Couzi
- Department of Nephrology, Transplantation and Dialysis, Bordeaux University Hospital, Bordeaux, France
| | - Lucrezia Furian
- Kidney and Pancreas Transplantation Unit, University of Padua, Padua, Italy
| | - Uwe Heemann
- Department of Nephrology, Technical University of Munich, Munich, Germany
| | - Nizam Mamode
- Department of Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
| | - Rainer Oberbauer
- Department of Nephrology and Dialysis, Medical University of Vienna, Vienna, Austria
| | - Liset Pengel
- Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom
| | - Stefan Schneeberger
- Department of General, Transplant, and Thoracic Surgery, Medical University of Innsbruck, Innsbruck, Austria
| | - Maarten Naesens
- Department of Microbiology, Immunology, and Transplantation, KU Leuven, Leuven, Belgium
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23
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Lepoittevin M, Giraud S, Kerforne T, Barrou B, Badet L, Bucur P, Salamé E, Goumard C, Savier E, Branchereau J, Battistella P, Mercier O, Mussot S, Hauet T, Thuillier R. Preservation of Organs to Be Transplanted: An Essential Step in the Transplant Process. Int J Mol Sci 2022; 23:ijms23094989. [PMID: 35563381 PMCID: PMC9104613 DOI: 10.3390/ijms23094989] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 04/25/2022] [Accepted: 04/27/2022] [Indexed: 12/23/2022] Open
Abstract
Organ transplantation remains the treatment of last resort in case of failure of a vital organ (lung, liver, heart, intestine) or non-vital organ (essentially the kidney and pancreas) for which supplementary treatments exist. It remains the best alternative both in terms of quality-of-life and life expectancy for patients and of public health expenditure. Unfortunately, organ shortage remains a widespread issue, as on average only about 25% of patients waiting for an organ are transplanted each year. This situation has led to the consideration of recent donor populations (deceased by brain death with extended criteria or deceased after circulatory arrest). These organs are sensitive to the conditions of conservation during the ischemia phase, which have an impact on the graft’s short- and long-term fate. This evolution necessitates a more adapted management of organ donation and the optimization of preservation conditions. In this general review, the different aspects of preservation will be considered. Initially done by hypothermia with the help of specific solutions, preservation is evolving with oxygenated perfusion, in hypothermia or normothermia, aiming at maintaining tissue metabolism. Preservation time is also becoming a unique evaluation window to predict organ quality, allowing repair and/or optimization of recipient choice.
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Affiliation(s)
- Maryne Lepoittevin
- Biochemistry Department, CHU Poitiers, 86021 Poitiers, France; (M.L.); (S.G.); (R.T.)
- Faculty of Medicine and Pharmacy, University of Poitiers, 86073 Poitiers, France;
- INSERM U1313, IRMETIST, 86021 Poitiers, France; (B.B.); (L.B.)
| | - Sébastien Giraud
- Biochemistry Department, CHU Poitiers, 86021 Poitiers, France; (M.L.); (S.G.); (R.T.)
- Faculty of Medicine and Pharmacy, University of Poitiers, 86073 Poitiers, France;
- INSERM U1313, IRMETIST, 86021 Poitiers, France; (B.B.); (L.B.)
| | - Thomas Kerforne
- Faculty of Medicine and Pharmacy, University of Poitiers, 86073 Poitiers, France;
- INSERM U1313, IRMETIST, 86021 Poitiers, France; (B.B.); (L.B.)
- Cardio-Thoracic and Vascular Surgery Intensive Care Unit, Coordination of P.M.O., CHU Poitiers, 86021 Poitiers, France
| | - Benoit Barrou
- INSERM U1313, IRMETIST, 86021 Poitiers, France; (B.B.); (L.B.)
- Sorbonne Université Campus Pierre et Marie Curie, Faculté de Médecine, 75005 Paris, France
- Service Médico-Chirurgical de Transplantation Rénale, APHP, Hôpital Pitié-Salpêtrière, 75013 Paris, France
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
| | - Lionel Badet
- INSERM U1313, IRMETIST, 86021 Poitiers, France; (B.B.); (L.B.)
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- Faculté de Médecine, Campus Lyon Santé Est, Université Claude Bernard, 69622 Lyon, France
- Service d’Urologie et Transplantation, Hospices Civils de Lyon, Hôpital Edouard-Herriot, 69003 Lyon, France
| | - Petru Bucur
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- Service de Chirurgie Digestive et Endocrinienne, Transplantation Hépatique, CHU de Tours, 37170 Chambray les Tours, France
- Groupement d’Imagerie Médicale, CHU de Tours, 37000 Tours, France
- University Hospital Federation SUPORT Tours Poitiers Limoges, 86021 Poitiers, France
| | - Ephrem Salamé
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- Service de Chirurgie Digestive et Endocrinienne, Transplantation Hépatique, CHU de Tours, 37170 Chambray les Tours, France
- Groupement d’Imagerie Médicale, CHU de Tours, 37000 Tours, France
- University Hospital Federation SUPORT Tours Poitiers Limoges, 86021 Poitiers, France
| | - Claire Goumard
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, APHP, Hôpital Pitié-Salpêtrière, 75013 Paris, France
| | - Eric Savier
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- Service de Chirurgie Digestive, Hépato-Bilio-Pancréatique et Transplantation Hépatique, APHP, Hôpital Pitié-Salpêtrière, 75013 Paris, France
| | - Julien Branchereau
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- Service d’Urologie et de Transplantation, CHU de Nantes, 44000 Nantes, France
| | - Pascal Battistella
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- Service de Cardiologie et Maladies Vasculaires, CHU de Montpellier, CEDEX 5, 34295 Montpellier, France
| | - Olaf Mercier
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- Service de Chirurgie Thoracique et Cardio-Vasculaire, Centre Chirurgical Marie LANNELONGUE, 92350 Le Plessis Robinson, France
| | - Sacha Mussot
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- Service de Chirurgie Thoracique et Cardio-Vasculaire, Centre Chirurgical Marie LANNELONGUE, 92350 Le Plessis Robinson, France
| | - Thierry Hauet
- Biochemistry Department, CHU Poitiers, 86021 Poitiers, France; (M.L.); (S.G.); (R.T.)
- Faculty of Medicine and Pharmacy, University of Poitiers, 86073 Poitiers, France;
- INSERM U1313, IRMETIST, 86021 Poitiers, France; (B.B.); (L.B.)
- Société Francophone de Transplantation et de l’Ecole Francophone pour le Prélèvement Multi-Organes, 75013 Paris, France; (P.B.); (E.S.); (C.G.); (E.S.); (J.B.); (P.B.); (O.M.); (S.M.)
- University Hospital Federation SUPORT Tours Poitiers Limoges, 86021 Poitiers, France
- Correspondence:
| | - Raphael Thuillier
- Biochemistry Department, CHU Poitiers, 86021 Poitiers, France; (M.L.); (S.G.); (R.T.)
- Faculty of Medicine and Pharmacy, University of Poitiers, 86073 Poitiers, France;
- INSERM U1313, IRMETIST, 86021 Poitiers, France; (B.B.); (L.B.)
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24
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Barreda Monteoliva P, Redondo-Pachón D, Miñambres García E, Rodrigo Calabia E. Kidney transplant outcome of expanded criteria donors after circulatory death. Nefrologia 2022; 42:135-144. [PMID: 36153910 DOI: 10.1016/j.nefroe.2021.01.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 01/31/2021] [Indexed: 06/16/2023] Open
Abstract
The increase in the number of patients on the kidney transplant waiting list has led to an attempt to increase the number of potential donors by incorporating candidates that previously would not have been considered optimal, including donors after cardiac death (DCD) and those with "expanded" criteria (ECD). Recipients of controlled DCD (cDCD) grafts suffer more delayed graft function (DGF), but have a long-term evolution comparable to those of brain-dead donors, which has allowed an increase in the number of cDCD transplants in different countries in recent years. In parallel, the use of cDCD with expanded criteria (cDCD/ECD) has increased in recent years in different countries, allowing the waiting list for kidney transplantation to be shortened. The use of these grafts, although associated with a higher frequency of DGF, offers similar or only slightly lower long-term graft survival than those of brain death donors with expanded criteria. Different studies have observed that cDCD/ECD graft recipients have worse kidney function than cDCD/standard and DBD/ECD. Mortality associated with cDCD/ECD graft transplantation mostly relates to the recipient age. Patients who receive a cDCD/≥60 graft have better survival than those who continue on the waiting list, although this fact has not been demonstrated in recipients of cDCD/>65 years. The use of this type of organ should be accompanied by the optimization of surgical times and the shortest possible cold ischemia.
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Affiliation(s)
- Paloma Barreda Monteoliva
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla/IDIVAL, Universidad de Cantabria, Santander, Spain
| | | | - Eduardo Miñambres García
- Coordinación de trasplantes, Hospital Universitario Marqués de Valdecilla/IDIVAL, Universidad de Cantabria, Santander, Spain
| | - Emilio Rodrigo Calabia
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla/IDIVAL, Universidad de Cantabria, Santander, Spain.
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25
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Rampino T, Gregorini M, Germinario G, Pattonieri EF, Erasmi F, Grignano MA, Bruno S, Alomari E, Bettati S, Asti A, Ramus M, De Amici M, Testa G, Bruno S, Ceccarelli G, Serpieri N, Libetta C, Sepe V, Blasevich F, Odaldi F, Maroni L, Vasuri F, La Manna G, Ravaioli M. Extracellular Vesicles Derived from Mesenchymal Stromal Cells Delivered during Hypothermic Oxygenated Machine Perfusion Repair Ischemic/Reperfusion Damage of Kidneys from Extended Criteria Donors. BIOLOGY 2022; 11:biology11030350. [PMID: 35336724 PMCID: PMC8945029 DOI: 10.3390/biology11030350] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/16/2022] [Accepted: 02/18/2022] [Indexed: 02/04/2023]
Abstract
Simple Summary In this study, we explore for the first time an innovative tool for organ preservation aimed to preventing ischemia reperfusion injury (IRI) in marginal kidneys from expanded criteria donors (ECD) unsuitable for transplantation. Ex vivo hypothermic oxygenated perfusion (HOPE) with and without MSC-derived EV and normothermic reperfusion (NR) with artificial blood composed of bovine hemoglobin were applied on kidneys to evaluate global renal ischemic damage score, renal ultrastructure, mitochondrial distress, apoptosis, cell proliferation index, and the mediators of energy metabolism. Our study demonstrates that kidney conditioning with HOPE+EV arrests the ischemic damage, prevents reoxygenation-dependent injury, and preserves tissue integrity. EV delivery during HOPE can be considered a new organ preservation strategy to increase the donor pool and improving transplant outcome. The originality of our study lies an EV and HOPE combined novel setting use in kidneys from ECD, but also in any condition for graft dysfunction such as ischemia/reperfusion. Abstract The poor availability of kidney for transplantation has led to a search for new strategies to increase the donor pool. The main option is the use of organs from extended criteria donors. We evaluated the effects of hypothermic oxygenated perfusion (HOPE) with and without extracellular vesicles (EV) derived from mesenchymal stromal cells on ischemic/reperfusion injury of marginal kidneys unsuitable for transplantation. For normothermic reperfusion (NR), we used artificial blood as a substitute for red blood cells. We evaluated the global renal ischemic dam-age score (GRS), analyzed the renal ultrastructure (RU), cytochrome c oxidase (COX) IV-1 (a mitochondrial distress marker), and caspase-3 renal expression, the tubular cell proliferation index, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) tissue levels, and effluent lactate and glucose levels. HOPE+EV kidneys had lower GRS and better RU, higher COX IV-1 expression and HGF and VEGF levels and lower caspase-3 expression than HOPE kidneys. During NR, HOPE+EV renal effluent had lower lactate release and higher glucose levels than HOPE renal effluent, suggesting that the gluconeogenesis system in HOPE+EV group was pre-served. In conclusion, EV delivery during HOPE can be considered a new organ preservation strategy for increasing the donor pool and improving transplant outcome.
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Affiliation(s)
- Teresa Rampino
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
| | - Marilena Gregorini
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
- Correspondence: ; Tel.: +39-0382-503896
| | - Giuliana Germinario
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (G.G.); (F.O.); (L.M.); (M.R.)
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), University of Bologna, 40126 Bologna, Italy
| | - Eleonora Francesca Pattonieri
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
| | - Fulvia Erasmi
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
| | - Maria Antonietta Grignano
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
| | - Stefano Bruno
- Department of Food and Drug, University of Parma, 43124 Parma, Italy; (S.B.); (E.A.)
- Biopharmatec TEC, University of Parma, Tecnopolo Padiglione 33, 43124 Parma, Italy;
| | - Esra Alomari
- Department of Food and Drug, University of Parma, 43124 Parma, Italy; (S.B.); (E.A.)
| | - Stefano Bettati
- Biopharmatec TEC, University of Parma, Tecnopolo Padiglione 33, 43124 Parma, Italy;
- Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy
| | - Annalia Asti
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
| | - Marina Ramus
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
| | - Mara De Amici
- Laboratory of Immuno-Allergology of Clinical Chemistry and Pediatric Clinic, Fondazione IRCCS Policlinico S. Matteo, 27100 Pavia, Italy;
| | - Giorgia Testa
- Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy;
| | - Stefania Bruno
- Department of Medical Sciences and Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy;
| | - Gabriele Ceccarelli
- Human Anatomy Unit, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy;
| | - Nicoletta Serpieri
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
| | - Carmelo Libetta
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
- Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, Italy
| | - Vincenzo Sepe
- Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy; (T.R.); (E.F.P.); (F.E.); (M.A.G.); (A.A.); (M.R.); (N.S.); (C.L.); (V.S.)
| | - Flavia Blasevich
- Department of Neuroimmunology and Neuromuscular Diseases, Fondazione IRCCS Neurological Institute Carlo Besta, 20133 Milan, Italy;
| | - Federica Odaldi
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (G.G.); (F.O.); (L.M.); (M.R.)
| | - Lorenzo Maroni
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (G.G.); (F.O.); (L.M.); (M.R.)
| | - Francesco Vasuri
- “F. Addarii” Institute of Oncology and Transplantation Pathology, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy;
| | - Gaetano La Manna
- Department of Nephrology, S.Orsola-Malpighi Hospital, University of Bologna, 40138 Bologna, Italy;
| | - Matteo Ravaioli
- Department of General Surgery and Transplantation, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (G.G.); (F.O.); (L.M.); (M.R.)
- Dipartimento di Scienze Mediche e Chirurgiche (DIMEC), University of Bologna, 40126 Bologna, Italy
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26
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Echterdiek F, Kitterer D, Dippon J, Ott M, Paul G, Latus J, Schwenger V. Outcome of kidney transplantations from ≥65-year-old deceased donors with acute kidney injury. Clin Transplant 2022; 36:e14612. [PMID: 35148007 DOI: 10.1111/ctr.14612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Revised: 02/02/2022] [Accepted: 02/03/2022] [Indexed: 11/30/2022]
Abstract
Kidney transplantation (KT) from donors with acute kidney injury (AKI) has been associated with delayed graft function (DGF) but similar graft survival compared with KT from donors without AKI. Kidneys from ≥65-year-old donors with comorbidities are more susceptible to cold ischemia time and DGF and it is unknown whether such elderly kidneys with AKI can also be transplanted with satisfactory outcomes. All KTs from ≥65-year-old donors performed at our centre from 1999 to 2019 (n = 233) were retrospectively analysed and short- as well as long-term outcomes were compared for KTs from donors with (n = 64) and without AKI (n = 169). There were no significant differences regarding the frequency of DGF as well as the estimated glomerular filtration rate (eGFR) one and three years post-transplant between the no-AKI and the AKI group (DGF: no-AKI 30.2% vs. AKI 40.6%, P = 0.17; eGFR at one-year: 31.9 ml/min/1.73m2 vs. 35.5 ml/min/1.73m2 , P = 0.32; at three-years: 33.8 ml/min/1.73m2 vs. 40.9 ml/min/1.73m2 , P = 0.18; respectively). Death-censored graft survival and patient survival were also not significantly different. Multivariable Cox regression analysis did not identify AKI as a significant risk factor for graft loss or death. Following careful donor and recipient selection, kidneys from ≥65-year-old AKI donors may potentially be transplanted with satisfactory outcomes. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Fabian Echterdiek
- Department of Nephrology, Klinikum Stuttgart - Katharinenhospital, Stuttgart, Germany
| | - Daniel Kitterer
- Department of Nephrology, Klinikum Stuttgart - Katharinenhospital, Stuttgart, Germany
| | - Jürgen Dippon
- Institute for Stochastics and Applications, University of Stuttgart, Germany
| | - Matthias Ott
- Department of Emergency and Intensive Care Medicine, Klinikum Stuttgart - Katharinenhospital, Stuttgart, Germany
| | - Gregor Paul
- Department of Gastroenterology, Hepatology, Pneumology and Infectious Diseases, Klinikum Stuttgart - Katharinenhospital, Stuttgart, Germany.,University of Cologne, Department I of Internal Medicine, Division of Infectious Diseases, Cologne, Germany
| | - Joerg Latus
- Department of Nephrology, Klinikum Stuttgart - Katharinenhospital, Stuttgart, Germany
| | - Vedat Schwenger
- Department of Nephrology, Klinikum Stuttgart - Katharinenhospital, Stuttgart, Germany
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Early Graft Loss Following Transplantation From Expanded Criteria Donors. Transplant Direct 2021; 7:e783. [PMID: 34712783 PMCID: PMC8547939 DOI: 10.1097/txd.0000000000001235] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/02/2021] [Accepted: 09/02/2021] [Indexed: 11/25/2022] Open
Abstract
Background Expanded criteria donor (ECD) kidneys are associated with higher graft loss rates than standard criteria donor kidneys. We sought to determine factors associated with early graft loss and their discrimination ability for this outcome compared with kidney donor risk index. Methods Data were extracted from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) for ECD transplants between 1997 and 2014. The primary outcome was early graft loss (all-cause graft loss within 3 y of transplantation). Death-censored graft loss was substituted as a sensitivity analysis. Era-adjusted odds ratios were calculated by multivariable logistic regression for donor, recipient, and transplant factors available at transplantation. Discrimination was assessed by c-statistic, with 95% confidence intervals (CIs) calculated by bootstrapping. Results Of 2152 ECD kidney transplants, early graft loss occurred in 406 (19%) and was associated with recipient diabetes, smoking, First Nations recipients, and oliguria. Of factors defining ECD (age, elevated terminal creatinine, hypertension, death from cerebrovascular accident), all but mode of death were associated with early graft loss. The multivariable model, including known donor, recipient, and transplant factors, was moderately good at predicting early graft loss (c-statistic 0.65; 95% CI, 0.62-0.68). Recipient factors (c-statistic 0.62; 95% CI, 0.59-0.65) performed equally well compared with donor factors (c-statistic 0.60; 95% CI, 0.57-0.64) or the kidney donor risk index (c-statistic 0.60; 95% CI, 0.56-0.63). Conclusions Early graft loss occurs in approximately one-fifth of ECD kidney transplants. The discriminatory value of commonly used recipient, donor, and transplant factors are approximately comparable and limited.
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Colas L, Bui L, Kerleau C, Lemdani M, Autain-Renaudin K, Magnan A, Giral M, Brouard S. Time-dependent blood eosinophilia count increases the risk of kidney allograft rejection. EBioMedicine 2021; 73:103645. [PMID: 34688031 PMCID: PMC8536518 DOI: 10.1016/j.ebiom.2021.103645] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 10/07/2021] [Accepted: 10/07/2021] [Indexed: 01/21/2023] Open
Abstract
Background Growing evidence suggest that type 2 immune effectors play a role in solid organ transplantation. The aim of this study was to evaluate the impact of blood count eosinophils (BCEo) on immunological outcomes in kidney transplant recipients with stable graft function after 3 months post-transplant. Method We performed cause-specific Cox model considering BCEo, the use of calcineurin inhibitors and systemic corticoids as time-dependent explicative variables on a prospective cohort of 1013 kidney transplant patients who experienced kidney allograft rejection and/or the appearance of de novo donor specific antibodies after excluding common causes of increased BCEo.. Findings BCEo ≥ 0.3 G/L was associated with a 3-fold increased risk of rejection independent of immunosuppressive regimen after 3 months post-transplant in patients without pre-transplant DSAs and with CNI-based immunosuppression. No association between BCEo either with donor specific antibodies or graft survival was noticed. Interpretation These observations in this large cohort support the hypothesis of eosinophils in allo-immunity in human and claim for further mechanistic research. Funding This study was supported by the French National Research Agency, The “Institut de Recherche en Santé Respiratoire des Pays de la Loire” and the University hospital of Nantes.
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Affiliation(s)
- Luc Colas
- INSERM, CHU Nantes, Nantes Université, Centre de Recherche en Transplantation et Immunologie UMR1064, Centre Hospitalier Universitaire de Nantes, ITUN 30 bd Jean Monnet, Nantes 44093, France
| | - Linh Bui
- Centre Hospitalier de Mouscron, Belgique, Service de néphrologie, Belgium
| | - Clarisse Kerleau
- Service de Néphrologie-Immunologie Clinique, CHU Nantes, Nantes Université, Nantes, France
| | - Mohamed Lemdani
- Département of Biomathematiques, Faculté de Pharmacie and Biologie, Université de Lille, Lille, France
| | - Karine Autain-Renaudin
- INSERM, CHU Nantes, Nantes Université, Centre de Recherche en Transplantation et Immunologie UMR1064, Centre Hospitalier Universitaire de Nantes, ITUN 30 bd Jean Monnet, Nantes 44093, France; Département d'anatomie et Cytologie Pathologique, CHU Nantes, Nantes Université, Nantes, France
| | - Antoine Magnan
- Université de Versailles Saint-Quentin Paris-Saclay, Hôpital Foch, INRAe UMR 0892, Paris, Suresnes, France
| | - Magali Giral
- INSERM, CHU Nantes, Nantes Université, Centre de Recherche en Transplantation et Immunologie UMR1064, Centre Hospitalier Universitaire de Nantes, ITUN 30 bd Jean Monnet, Nantes 44093, France; Service de Néphrologie-Immunologie Clinique, CHU Nantes, Nantes Université, Nantes, France; Labex IGO, F-44000 Nantes, France.; Centre d'Investigation Clinique en Biothérapie, Institut de Transplantation Urology and Nephrology (ITUN), Centre Hospitalier Universitaire de Nantes, 30 bd Jean Monnet, Nantes 44093, France.
| | - Sophie Brouard
- INSERM, CHU Nantes, Nantes Université, Centre de Recherche en Transplantation et Immunologie UMR1064, Centre Hospitalier Universitaire de Nantes, ITUN 30 bd Jean Monnet, Nantes 44093, France; Labex IGO, F-44000 Nantes, France.; Centre d'Investigation Clinique en Biothérapie, Institut de Transplantation Urology and Nephrology (ITUN), Centre Hospitalier Universitaire de Nantes, 30 bd Jean Monnet, Nantes 44093, France.
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29
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Hao C, Zhang J, Zhang F, Wu J, Cao H, Wang W. Mitochondrial DNA may act as a biomarker to predict donor-kidney quality. Clin Transplant 2021; 35:e14469. [PMID: 34448256 DOI: 10.1111/ctr.14469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 08/13/2021] [Accepted: 08/18/2021] [Indexed: 11/29/2022]
Abstract
Kidney transplantation is the best therapy for end-stage renal disease. Demand for kidney transplantation rises year-on-year, and the gap between kidney supply and demand remains large. To meet this clinical need, a gradual expansion in the supply of donors is required. However, clinics lack appropriate tools capable of quickly and accurately predicting post-transplant renal allograft function, and thus assess donor-kidney quality before transplantation. Mitochondrial DNA (mtDNA) is a key component of damage-associated molecular patterns (DAMPs) and plays an important part in ischemia-reperfusion injury (IRI), accelerating the progression of IRI by inducing inflammation and type I interferon responses. mtDNA is known to be closely involved in delayed graft function (DGF) and acute kidney injury (AKI) after transplantation. Thus, mtDNA is a potential biomarker able to predict post-transplant renal allograft function. This review summarizes mtDNA biology, the role mtDNA plays in renal transplantation, outlines advances in detecting mtDNA, and details mtDNA's able to predict post-transplant renal allograft function. We aim to elucidate the potential value of mtDNA as a biomarker in the prediction of IRI, and eventually provide help for predicting donor-kidney quality.
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Affiliation(s)
- Changzhen Hao
- Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.,Institute of Urology, Capital Medical University, Beijing, China
| | - Jiandong Zhang
- Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.,Institute of Urology, Capital Medical University, Beijing, China
| | - Feilong Zhang
- Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.,Institute of Urology, Capital Medical University, Beijing, China
| | - Jiyue Wu
- Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.,Institute of Urology, Capital Medical University, Beijing, China
| | - Huawei Cao
- Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.,Institute of Urology, Capital Medical University, Beijing, China
| | - Wei Wang
- Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.,Institute of Urology, Capital Medical University, Beijing, China
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30
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Barreda Monteoliva P, Redondo-Pachón D, Miñambres García E, Rodrigo Calabria E. Kidney transplant outcome of expanded criteria donors after circulatory death. Nefrologia 2021; 42:S0211-6995(21)00104-1. [PMID: 34154848 DOI: 10.1016/j.nefro.2021.01.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 01/30/2021] [Accepted: 01/31/2021] [Indexed: 10/21/2022] Open
Abstract
The increase in the number of patients on the kidney transplant waiting list has led to an attempt to increase the number of potential donors by incorporating candidates that previously would not have been considered optimal, including donors after cardiac death (DCD) and those with "expanded" criteria (ECD). Recipients of controlled DCD (cDCD) grafts suffer more delayed graft function (DGF), but have a long-term evolution comparable to those of brain-dead donors, which has allowed an increase in the number of cDCD transplants in different countries in recent years. In parallel, the use of cDCD with expanded criteria (cDCD/ECD) has increased in recent years in different countries, allowing the waiting list for kidney transplantation to be shortened. The use of these grafts, although associated with a higher frequency of DGF, offers similar or only slightly lower long-term graft survival than those of brain death donors with expanded criteria. Different studies have observed that cDCD/ECD graft recipients have worse kidney function than cDCD/standard and brain death/ECD. Mortality associated with cDCD/ECD graft transplantation mostly relates to the recipient age. Patients who receive a cDCD/≥60 graft have better survival than those who continue on the waiting list, although this fact has not been demonstrated in recipients of cDCD/>65 years. The use of this type of organ should be accompanied by the optimization of surgical times and the shortest possible cold ischemia.
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Affiliation(s)
- Paloma Barreda Monteoliva
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla/IDIVAL, Universidad de Cantabria, Santander, España
| | | | - Eduardo Miñambres García
- Coordinación de trasplantes, Hospital Universitario Marqués de Valdecilla/IDIVAL, Universidad de Cantabria, Santander, España
| | - Emilio Rodrigo Calabria
- Servicio de Nefrología, Hospital Universitario Marqués de Valdecilla/IDIVAL, Universidad de Cantabria, Santander, España.
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31
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Novel Insights into the Molecular Mechanisms of Ischemia/Reperfusion Injury in Kidney Transplantation. TRANSPLANTOLOGY 2021. [DOI: 10.3390/transplantology2020018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Ischemia reperfusion injury (IRI) is one of the most important mechanisms involved in delayed or reduced graft function after kidney transplantation. It is a complex pathophysiological process, followed by a pro-inflammatory response that enhances the immunogenicity of the graft and the risk of acute rejection. Many biologic processes are involved in its development, such as transcriptional reprogramming, the activation of apoptosis and cell death, endothelial dysfunction and the activation of the innate and adaptive immune response. Recent evidence has highlighted the importance of complement activation in IRI cascade, which expresses a pleiotropic action on tubular cells, on vascular cells (pericytes and endothelial cells) and on immune system cells. The effects of IRI in the long term lead to interstitial fibrosis and tubular atrophy, which contribute to chronic graft dysfunction and subsequently graft failure. Furthermore, several metabolic alterations occur upon IRI. Metabolomic analyses of IRI detected a “metabolic profile” of this process, in order to identify novel biomarkers that may potentially be useful for both early diagnosis and monitoring the therapeutic response. The aim of this review is to update the most relevant molecular mechanisms underlying IRI, and also to discuss potential therapeutic targets in future clinical practice.
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32
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Renal Resistance Trend During Hypothermic Machine Perfusion Correlates With Preimplantation Biopsy Score in Transplantation of Kidneys From Extended Criteria Donors. Transplant Proc 2021; 53:1823-1830. [PMID: 33965240 DOI: 10.1016/j.transproceed.2021.03.036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 03/01/2021] [Accepted: 03/17/2021] [Indexed: 11/21/2022]
Abstract
BACKGROUND Graft quality from extended criteria donors (ECDs) is extremely wide, and a reliable evaluation parameter is required. So far, biopsy is widely used to evaluate ECD organs and to decide whether double (DKT) or single (SKT) kidney transplantation should be performed. The aim of this study is to compare renal resistance (RR) trend during hypothermic machine perfusion (HMP) with a preimplantation biopsy score. METHODS From December 2014 to April 2020, HMP has been systematically applied to all organs from ECDs for at least 3 hours. All grafts underwent a preimplantation biopsy histologic assessment with Karpinski's score. SKTs or DKTs were performed accordingly. RR trend during the first 180 minutes of HMP was compared with the biopsy score. RESULTS Eighty-three kidneys were used to perform 57 transplantations (31 SKTs and 26 DKTs). A biopsy confirmed suitability for transplantation in all cases, and the median score was 4 (range, 2-7). Kidneys with a score of 5 to 7 had significantly higher RR value than kidneys with a score of 0 to 4 at basal time (3.35 vs 2.71; P = .074), at 60 minutes (1.24 vs 0.94; P = .031), at 120 minutes (1.10 vs 0.81; P = .010), and at 180 minutes (1.00 vs 0.77; P = .022). A cutoff value of RR ≥0.88 at 120 minutes of perfusion had the best sensibility and specificity (0.71 and 0.75, respectively) to discriminate kidneys with a score of 5 to 7 from kidneys with a score of 0 to 4. No differences were found in postoperative outcomes between SKT and DKT recipients. CONCLUSIONS RR trend during HMP correlates with the histologic score in ECD kidneys and can be used as a reliable parameter to evaluate graft quality.
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33
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Mendez NV, Raveh Y, Livingstone JJ, Ciancio G, Guerra G, Burke III GW, Shatz VB, Souki FG, Chen LJ, Morsi M, Figueiro JM, Ibrahim TM, DeFaria WL, Nicolau-Raducu R. Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation: A retrospective, single center study. World J Transplant 2021; 11:114-128. [PMID: 33954089 PMCID: PMC8058644 DOI: 10.5500/wjt.v11.i4.114] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 02/05/2021] [Accepted: 03/11/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation (DDKT) to address the high incidence of kidney failure. Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients; thus the identification of modifiable risk factors associated with poor outcomes is paramount.
AIM To identify risk factors associated with delayed graft function (DGF).
METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients. The primary outcome was the occurrence of DGF.
RESULTS The incidence of DGF was 27%. Under logistic regression, eight independent risk factors for DGF were identified including recipient body mass index ≥ 30 kg/m2, baseline mean arterial pressure < 110 mmHg, intraoperative phenylephrine administration, cold storage time ≥ 16 h, donation after cardiac death, donor history of coronary artery disease, donor terminal creatinine ≥ 1.9 mg/dL, and a hypothermic machine perfusion (HMP) pump resistance ≥ 0.23 mmHg/mL/min.
CONCLUSION We delineate the association between DGF and recipient characteristics of pre-induction mean arterial pressure below 110 mmHg, metabolic syndrome, donor-specific risk factors, HMP pump parameters, and intraoperative use of phenylephrine.
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Affiliation(s)
- Nicholas V Mendez
- Department of Anesthesiology, University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Yehuda Raveh
- Department of Anesthesiology, University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Joshua J Livingstone
- Department of Anesthesiology, University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Gaetano Ciancio
- Department of Surgery, Miami Transplant Institute/University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Giselle Guerra
- Division of Nephrology of the Department of Medicine, University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - George W Burke III
- Department of Surgery, Miami Transplant Institute/University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Vadim B Shatz
- Department of Anesthesiology, University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Fouad G Souki
- Department of Anesthesiology, University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Linda J Chen
- Department of Surgery, Miami Transplant Institute/University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Mahmoud Morsi
- Department of Surgery, Miami Transplant Institute/University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Jose M Figueiro
- Department of Surgery, Miami Transplant Institute/University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Tony M Ibrahim
- Department of Surgery, Miami Transplant Institute/University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Werviston L DeFaria
- Department of Surgery, Miami Transplant Institute/University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
| | - Ramona Nicolau-Raducu
- Department of Anesthesiology, University of Miami/Jackson Memorial Hospital, Miami, FL 33136, United States
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34
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Kizilbash SJ, Evans MD, Chinnakotla S, Chavers BM. Use of expanded-criteria donors and > 85 KDPI kidneys for pediatric kidney transplantation in the United States. Am J Transplant 2021; 21:1160-1170. [PMID: 32594613 PMCID: PMC7767891 DOI: 10.1111/ajt.16162] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 06/11/2020] [Accepted: 06/13/2020] [Indexed: 01/25/2023]
Abstract
Pediatric kidney transplant outcomes associated with expanded-criteria donors (ECD) and high Kidney Donor Profile Index (KDPI) kidneys are unknown. We reviewed the Scientific Registry of Transplant Recipients data from 1987-2017 to identify 96 ECD and 92 > 85 KDPI kidney recipients (<18 years). Using propensity scores, we created comparison groups of 375 non-ECD and 357 ≤ 85 KDPI recipients for comparisons with ECD and > 85 KDPI transplants, respectively. We used Cox regression for patient/graft survival and sequential Cox approach for survival benefit of ECD and > 85 KDPI transplantationvs remaining on the waitlist. After adjustment, ECD recipients were at significantly increased risk of graft failure (adjusted hazard ratio [aHR] = 1.6; P = .001) but not of mortality (aHR = 1.33; P = .15) compared with non-ECD recipients. We observed no survival benefit of ECD transplants vs remaining on the waitlist (aHR = 1.05; P = .83). We found no significant difference in graft failure (aHR = 1.27; P = .12) and mortality (aHR = 1.41; P = .13) risks between > 85 KDPI and ≤ 85 KDPI recipients. However, > 85 KDPI transplants were associated with a survival benefit vs remaining on the waitlist (aHR = 0.41; P = .01). ECD transplantation in children is associated with a high graft loss risk and no survival benefit, whereas > 85 KDPI transplantation is associated with a survival benefit for children vs remaining on the waitlist.
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Affiliation(s)
- Sarah J. Kizilbash
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
| | - Michael D. Evans
- Clinical and Translational Science institute, University of Minnesota, Minneapolis, Minnesota
| | | | - Blanche M. Chavers
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
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35
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Pearson R, Asher J, Jackson A, Mark PB, Shumeyko V, Clancy MJ. Viability assessment and utilization of declined donor kidneys with rhabdomyolysis using ex vivo normothermic perfusion without preimplantation biopsy. Am J Transplant 2021; 21:1317-1321. [PMID: 33021059 DOI: 10.1111/ajt.16329] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Revised: 09/11/2020] [Accepted: 09/14/2020] [Indexed: 01/25/2023]
Abstract
The role of ex vivo normothermic perfusion (EVNP) in both organ viability assessment and reconditioning is increasingly being demonstrated. We report the use of this emerging technology to facilitate the transplantation of a pair of donor kidneys with severe acute kidney injury (AKI) secondary to rhabdomyolysis. Donor creatinine was 10.18 mg/dl with protein (30 mg/dl) present in urinalysis. Both kidneys were declined by all other transplantation units and subsequently accepted by our unit. The first kidney was perfused with red cell-based perfusate at 37°C for 75 min, mean renal blood flow was 110 ml/min/100 g and produced 85 ml of urine. Having demonstrated favorable macroscopic appearance and urine output, the kidney was transplanted into a 61-year-old peritoneal dialysis dependent without complication. Given the reassuring information from the first kidney provided by EVNP, the second kidney was not perfused with EVNP and was directly implanted to a 64-year-old patient. The first kidney achieved primary function and the second functioned well after delayed graft function. Recipient eGFR have stabilized at 88.5 and 55.3, respectively (ml/min/1.73 m2 ), at 2 months posttransplant.
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Affiliation(s)
| | - John Asher
- Queen Elizabeth University Hospital, Glasgow, UK
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36
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Vincenzi P, Gonzalez J, Guerra G, Gaynor JJ, Alvarez A, Ciancio G. Complex Surgical Reconstruction of Upper Pole Artery in Living-Donor Kidney Transplantation. Ann Transplant 2021; 26:e926850. [PMID: 33446626 PMCID: PMC7814512 DOI: 10.12659/aot.926850] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background The use of allografts with multiple renal arteries has increased in the era of laparoscopic donor nephrectomy. Although several studies recommend reconstructing lower pole arteries (LPAs) to reduce risk of urologic complications, it is common opinion to ligate upper pole arteries (UPAs) with a diameter less than 2 mm because of increased risk of thrombosis related to their reconstruction. This retrospective study evaluates the feasibility and safety of reconstructing thin UPAs during living-donor kidney transplantation, with the goal of maintaining the integrity of the graft and assuring its maximal function. Material/Methods Data from 922 living-donor kidney transplants performed between 2009 and 2019 were reviewed. Six cases with UPAs were identified (0.65%). The study endpoints were incidence of allograft vascular and urologic complications, slow graft function, delayed graft function, graft failure, and graft and patient survival. Results The UPAs had a mean diameter of 1.8±0.28 mm. Methods of reconstruction included: interposition graft (n=2), end-to-side anastomosis inside the renal hilum to a branch of the main renal artery (n=3), and side-to-side anastomosis with the main renal artery (n=1). Additional reconstruction of LPAs (n=2) and main renal arteries (n=2) was performed. During a median (range) follow-up of 14.5 (9–49) months no complications were observed. Conclusions Ex vivo reconstruction of UPAs with a diameter less than 2 mm is worth attempting, particularly in the setting of living-donor kidney transplantation.
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Affiliation(s)
- Paolo Vincenzi
- Department of Surgery, Miami Transplant Institute, Miami, FL, USA.,University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA
| | - Javier Gonzalez
- Department of Urology, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Giselle Guerra
- University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA.,Department of Medicine, Division of Nephrology, Miami Transplant Institute, Miami, FL, USA
| | - Jeffrey J Gaynor
- Department of Surgery, Miami Transplant Institute, Miami, FL, USA.,University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA
| | - Angel Alvarez
- Department of Surgery, Miami Transplant Institute, Miami, FL, USA
| | - Gaetano Ciancio
- Department of Surgery, Miami Transplant Institute, Miami, FL, USA.,University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA.,Department of Urology, Miami Transplant Institute, Miami, FL, USA
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37
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Does HLA matching matter in the modern era of renal transplantation? Pediatr Nephrol 2021; 36:31-40. [PMID: 31820146 PMCID: PMC7701071 DOI: 10.1007/s00467-019-04393-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 07/02/2019] [Accepted: 09/06/2019] [Indexed: 01/10/2023]
Abstract
Children with end-stage kidney disease should be offered the best chance for future survival which ideally would be a well-matched pre-emptive kidney transplant. Paediatric and adult practice varies around the world depending on geography, transplant allocation schemes and different emphases on living (versus deceased) donor renal transplantation. Internationally, paediatric patients often have priority in allocation schemes and younger donors are preferentially allocated to paediatric recipients. HLA matching can be difficult and may result in longer waiting times. Additionally, with improved surgical techniques and modern immunosuppressive regimens, how important is the contribution of HLA matching to graft longevity? In this review, we discuss the relative importance of HLA matching compared with donor quality; and long-term patient outcomes including re-transplantation rates. We share empirical evidence that will be useful for clinicians and families to make decisions about best donor options. We discuss why living donation still provides the best allograft survival outcomes and what to do in the scenario of a highly mismatched living donor.
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Development and external validation study combining existing models and recent data into an up-to-date prediction model for evaluating kidneys from older deceased donors for transplantation. Kidney Int 2020; 99:1459-1469. [PMID: 33340517 DOI: 10.1016/j.kint.2020.11.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 10/11/2020] [Accepted: 11/05/2020] [Indexed: 11/20/2022]
Abstract
With a rising demand for kidney transplantation, reliable pre-transplant assessment of organ quality becomes top priority. In clinical practice, physicians are regularly in doubt whether suboptimal kidney offers from older donors should be accepted. Here, we externally validate existing prediction models in a European population of older deceased donors, and subsequently developed and externally validated an adverse outcome prediction tool. Recipients of kidney grafts from deceased donors 50 years of age and older were included from the Netherlands Organ Transplant Registry (NOTR) and United States organ transplant registry from 2006-2018. The predicted adverse outcome was a composite of graft failure, death or chronic kidney disease stage 4 plus within one year after transplantation, modelled using logistic regression. Discrimination and calibration were assessed in internal, temporal and external validation. Seven existing models were validated with the same cohorts. The NOTR development cohort contained 2510 patients and 823 events. The temporal validation within NOTR had 837 patients and the external validation used 31987 patients in the United States organ transplant registry. Discrimination of our full adverse outcome model was moderate in external validation (C-statistic 0.63), though somewhat better than discrimination of the seven existing prediction models (average C-statistic 0.57). The model's calibration was highly accurate. Thus, since existing adverse outcome kidney graft survival models performed poorly in a population of older deceased donors, novel models were developed and externally validated, with maximum achievable performance in a population of older deceased kidney donors. These models could assist transplant clinicians in deciding whether to accept a kidney from an older donor.
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Dujardin A, Lorent M, Foucher Y, Legendre C, Kerleau C, Brouard S, Giral M. Time-dependent lymphocyte count after transplantation is associated with higher risk of graft failure and death. Kidney Int 2020; 99:1189-1201. [PMID: 32891605 DOI: 10.1016/j.kint.2020.08.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Revised: 07/11/2020] [Accepted: 08/10/2020] [Indexed: 11/18/2022]
Abstract
The transplantation field requires the identification of specific risk factors associated with the level of immunosuppression. Here, our aim was to analyze the association between the number of circulating lymphocytes, monitored routinely by complete blood cell counts during outpatient visits, and patient and graft survival. In total, 2,999 kidney or combined kidney-pancreas recipients transplanted between 2000 and 2016, from two University hospitals, were enrolled. We investigated the etiological relationship between time-dependent lymphocyte count beyond one year after transplantation and patient and graft survival, viral infection and cancer risk using time-dependent multivariate Cox models. Model 1 considered kidney function at one year and model 2 as time-dependent variable. At the time of inclusion (one year after transplantation), 584 patients (19.4%) had deep lymphopenia (under 750 /mm3) and 1,072 (35.7%) had a normal count (over 1,500 /mm3). A patient with deep lymphopenia at a given follow-up time had significantly higher risks of graft failure, death and viral infection than comparable patients with a normal lymphocyte count at the same time point. Thus, after the first year of transplantation, the occurrence of deep lymphopenia within a patient's follow-up is a risk factor for long-term graft failure, death and viral infection.
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Affiliation(s)
- Amaury Dujardin
- CRTI UMR 1064, Inserm, Université de Nantes, ITUN, CHU Nantes, RTRS Centaure, Nantes, France; Centre Hospitalier Universitaire de Nantes, Nantes, France
| | - Marine Lorent
- Centre Hospitalier Universitaire de Nantes, Nantes, France; Inserm UMR 1246-SPHERE, Université de Nantes, Université de Tours, Nantes, France
| | - Yohann Foucher
- Centre Hospitalier Universitaire de Nantes, Nantes, France; Inserm UMR 1246-SPHERE, Université de Nantes, Université de Tours, Nantes, France
| | - Christophe Legendre
- Kidney Transplant Center, Necker University Hospital, APHP, RTRS Centaure, Paris Descartes and Sorbonne Paris Cité Universities, Paris, France
| | | | - Sophie Brouard
- CRTI UMR 1064, Inserm, Université de Nantes, ITUN, CHU Nantes, RTRS Centaure, Nantes, France; Centre Hospitalier Universitaire de Nantes, Nantes, France.
| | - Magali Giral
- CRTI UMR 1064, Inserm, Université de Nantes, ITUN, CHU Nantes, RTRS Centaure, Nantes, France; Centre Hospitalier Universitaire de Nantes, Nantes, France; Centre d'Investigation Clinique en Biothérapie, Labex IGO, Nantes, France
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Hypothermic Oxygenated New Machine Perfusion System in Liver and Kidney Transplantation of Extended Criteria Donors:First Italian Clinical Trial. Sci Rep 2020; 10:6063. [PMID: 32269237 PMCID: PMC7142134 DOI: 10.1038/s41598-020-62979-9] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 03/04/2020] [Indexed: 02/08/2023] Open
Abstract
With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs. 31.7%, in SCS group (p = 0.05). Primary non-function was 3.3% for SCS-L vs. 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs.344 U/L, p = 0.007). Graft survival at 1-year post-transplant was 93.3% for SCS-L vs. 100% of HOPE-L and 90% for SCS-K vs. 100% of HOPE-K. Clinical outcomes support our hypothesis of machine perfusion being a safe and effective system to reduce ischemic preservation injuries in KT and in LT.
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Favi E, James A, Puliatti C, Whatling P, Ferraresso M, Rui C, Cacciola R. Utility and safety of early allograft biopsy in adult deceased donor kidney transplant recipients. Clin Exp Nephrol 2020; 24:356-368. [PMID: 31768863 DOI: 10.1007/s10157-019-01821-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Accepted: 11/12/2019] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Delayed graft function (DGF) is considered a risk factor for rejection after kidney transplantation (KTx). Clinical guidelines recommend weekly allograft biopsy until DGF resolves. However, who may benefit the most from such an aggressive policy and when histology should be evaluated remain debated. METHODS We analyzed 223 biopsies in 145 deceased donor KTx treated with basiliximab or anti-thymocyte globulin (rATG) and calcineurin inhibitor-based maintenance. The aim of the study was to assess the utility and safety of biopsies performed within 28 days of transplant. Relationships between transplant characteristics, indication, timing, and biopsy-related outcomes were evaluated. RESULTS Main indication for biopsy was DGF (87.8%) followed by lack of improvement in graft function (9.2%), and worsening graft function (3.1%). Acute tubular necrosis was the leading diagnosis (89.8%) whereas rejection was detected in 8.2% specimens. Rejection was more frequent in patients biopsied due to worsening graft function or lack of improvement in graft function than DGF (66.7% vs. 3.5%; P = 0.0075 and 33.3% vs. 3.5%; P = 0.0104, respectively) and in biopsies performed between day 15 and 28 than from day 0 to 14 (31.2% vs. 3.7%; P = 0.0002). Complication rate was 4.1%. Management was affected by the information gained with histology in 12.2% cases (7% considering DGF). CONCLUSIONS In low-immunological risk recipients treated with induction and calcineurin inhibitors maintenance, protocol biopsies obtained within 2 weeks of surgery to rule out rejection during DGF do not necessarily offer a favourable balance between risks and benefits. In these patients, a tailored approach may minimize complications thus optimizing results.
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Affiliation(s)
- Evaldo Favi
- Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza n. 35, 20122, Milan, Italy.
| | - Ajith James
- Nephrology, Royal London Hospital, Barts Health NHS Trust, Whitechapel Rd, London, E1 1BB, UK
| | - Carmelo Puliatti
- Organ Transplantation, Parma University Hospital, Via A. Gramsci 14, 43126, Parma, Italy
| | - Phil Whatling
- Nephrology, Royal London Hospital, Barts Health NHS Trust, Whitechapel Rd, London, E1 1BB, UK
| | - Mariano Ferraresso
- Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza n. 35, 20122, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy
| | - Chiara Rui
- Renal Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via Francesco Sforza n. 35, 20122, Milan, Italy
| | - Roberto Cacciola
- HPB and Transplant Unit, Department of Surgery, Tor Vergata University, Viale Oxford 81, 00133, Rome, Italy
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Bisigniano L, Tagliafichi V, Antik A. Validation of the Kidney Donor Profile Index in Argentina. Transplant Proc 2020; 52:1049-1052. [PMID: 32217013 DOI: 10.1016/j.transproceed.2020.01.058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 01/22/2020] [Indexed: 10/24/2022]
Abstract
Kidney Donor Profile Index (KDPI), derived from donor characteristics, was developed in the United States in an effort to devise an objective means of assessing donor organ suitability based on predicted graft survival. The objective of this study is to analyze the utility of KDPI to predict renal graft survival in Argentina. We conducted a retrospective national cohort study of adult patients who received a deceased donor renal transplantation in Argentina between January 2008 and December 2017. The graft survival was estimated according to the KDPI stratified by quartiles. A Kaplan-Meier analysis was used to calculate survival. A Cox regression was performed to estimate the probability of graft loss for each quart of the KDPI adjusted by receptor variables (age, diabetes, sex, and dialysis time) and cold ischemia time. In a Kaplan-Meier analysis, the graft survival decreases as the quartile of KDPI increases. Multivariate analysis shows that the increase in KDPI quartile and recipient's characteristics-such as age ≥60 years, diabetes, and dialysis time-were related to the probability of graft loss. In conclusion, the KDPI system could provide a guide to objectively assess the quality of organs offered for transplantation in Argentina.
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Affiliation(s)
- Liliana Bisigniano
- Department of Scientific and Technical Direction, Instituto Nacional Central Único Coordinador de Ablación e Implante (INCUCAI), Buenos Aires, Argentina
| | - Viviana Tagliafichi
- Department of Scientific and Technical Direction, Instituto Nacional Central Único Coordinador de Ablación e Implante (INCUCAI), Buenos Aires, Argentina
| | - Ariel Antik
- Department of Scientific and Technical Direction, Instituto Nacional Central Único Coordinador de Ablación e Implante (INCUCAI), Buenos Aires, Argentina.
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Hruba P, Krejcik Z, Dostalova Merkerova M, Klema J, Stranecky V, Slatinska J, Maluskova J, Honsova E, Viklicky O. Molecular Fingerprints of Borderline Changes in Kidney Allografts Are Influenced by Donor Category. Front Immunol 2020; 11:423. [PMID: 32269565 PMCID: PMC7109293 DOI: 10.3389/fimmu.2020.00423] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 02/24/2020] [Indexed: 11/13/2022] Open
Abstract
The fate of transplanted kidneys is substantially influenced by graft quality, with transplantation of kidneys from elderly and expanded criteria donors (ECDs) associated with higher occurrence of delayed graft function, rejection, and inferior long-term outcomes. However, little is known about early molecular fingerprints of these events in different donor categories. Borderline changes represent the most frequent histological finding early after kidney transplantation. Therefore, we examined outcomes and transcriptomic profiles of early-case biopsies diagnosed as borderline changes in different donor categories. In this single-center, retrospective, observational study, we compared midterm outcomes of kidney transplant recipients with early borderline changes as a first pathology between ECD (n = 109), standard criteria donor (SCDs, n = 109), and living donor (LD, n = 51) cohorts. Intragraft gene expression profiling by microarray was performed in part of these ECD, SCD, and LD cohorts. Although 5 year graft survival in patients with borderline changes in early-case biopsies was not influenced by donor category (log-rank P = 0.293), impaired kidney graft function (estimated glomerular filtration rate by Chronic Kidney Disease Epidemiology Collaboration equation) at M3, 1, 2, and 3 years was observed in the ECD cohort (P < 0.001). Graft biopsies from ECD donors had higher vascular intimal fibrosis and arteriolar hyalinosis compared to SCD and LD (P < 0.001), suggesting chronic vascular changes. Increased transcripts typical for ECD, as compared to both LD and SCD, showed enrichment of the inflammatory, defense, and wounding responses and the ECM-receptor interaction pathway. Additionally, increased transcripts in ECD vs. LD showed activation of complement and coagulation and cytokine-cytokine receptor pathways along with platelet activation and cell cycle regulation. Comparative gene expression overlaps of ECD, SCD, and LD using Venn diagrams found 64 up- and 16 down-regulated genes in ECD compared to both LD and SCD. Shared increased transcripts in ECD vs. both SCD and LD included thrombospondin-2 (THBS2), angiopoietin-like 4 (ANGPTL4), collagens (COL6A3, COL1A1), chemokine CCL13, and interleukin IL11, and most significantly, down-regulated transcripts included proline-rich 35 (PRR35) and fibroblast growth factor 9. Early borderline changes in ECD kidney transplantation are characterized by increased regulation of inflammation, extracellular matrix remodeling, and acute kidney injury transcripts in comparison with both LD and SCD grafts.
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Affiliation(s)
- Petra Hruba
- Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czechia
| | - Zdenek Krejcik
- Department of Genomics, Institute of Haematology and Blood Transfusion, Prague, Czechia
| | | | - Jiri Klema
- Department of Computer Science, Faculty of Electrical Engineering, Czech Technical University, Prague, Czechia
| | - Viktor Stranecky
- Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University, Prague, Czechia
| | - Janka Slatinska
- Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czechia
| | - Jana Maluskova
- Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czechia
| | - Eva Honsova
- Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czechia
| | - Ondrej Viklicky
- Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czechia.,Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czechia
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Graham JA, Torabi J, Ajaimy M, Akalin E, Liriano LE, Azzi Y, Pynadath C, Greenstein SM, Goldstein DY, Fox AS, Weiss JM, Powell TP, Reinus JF, Kinkhabwala MM, Rocca JP. Transplantation of viral-positive hepatitis C-positive kidneys into uninfected recipients offers an opportunity to increase organ access. Clin Transplant 2020; 34:e13833. [PMID: 32072689 DOI: 10.1111/ctr.13833] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 02/06/2020] [Accepted: 02/13/2020] [Indexed: 12/26/2022]
Abstract
The advent of direct-acting antivirals (DAAs) has provided the impetus to transplant kidneys from hepatitis C virus-positive donors into uninfected recipients (D+/R-). Thirty D+/R- patients received DAA treatment. Sustained virologic response (SVR12) was defined as an undetectable viral load in 12 weeks after treatment. An age-matched cohort of uninfected donor and recipient pairs (D-/R-) transplanted during same time period was used for comparison. The median day of viral detection was postoperative day (POD) 2. The detection of viremia in D+/R- patients was 100%. The initial median viral load was 531 copies/μL (range: 10-1 × 108 copies/μL) with a median peak viral load of 3.4 × 105 copies/μL (range: 804-1.0 × 108 copies/μL). DAAs were initiated on median POD 9 (range: 5-41 days). All 30 patients had confirmed SVR12. During a median follow-up of 10 months, patient and graft survival was 100%, and acute rejection was 6.6% with no major adverse events related to DAA treatment. Delayed graft function was significantly decreased in D+/R- patients as compared to the age-matched cohort (27% vs 60%; P = .01). D+/R- transplantation offers patients an alternative strategy to increase access.
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Affiliation(s)
- Jay A Graham
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
| | - Julia Torabi
- Albert Einstein College of Medicine, Bronx, NY, USA
| | - Maria Ajaimy
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
| | - Enver Akalin
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
| | - Luz E Liriano
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
| | - Yorg Azzi
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
| | - Cindy Pynadath
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
| | - Stuart M Greenstein
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
| | - Doctor Y Goldstein
- Albert Einstein College of Medicine, Bronx, NY, USA.,Department of Pathology, Montefiore Medical Center, Bronx, NY, USA
| | - Amy S Fox
- Albert Einstein College of Medicine, Bronx, NY, USA.,Department of Pathology, Montefiore Medical Center, Bronx, NY, USA
| | - Jeffery M Weiss
- Albert Einstein College of Medicine, Bronx, NY, USA.,Department of Medicine, Montefiore Medical Center, Bronx, NY, USA
| | - Tia P Powell
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Bioethics, Montefiore Medical Center, Bronx, NY, USA
| | - John F Reinus
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
| | - Milan M Kinkhabwala
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
| | - Juan P Rocca
- Albert Einstein College of Medicine, Bronx, NY, USA.,Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, Bronx, NY, USA
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Noble J, Jouve T, Malvezzi P, Süsal C, Rostaing L. Transplantation of Marginal Organs: Immunological Aspects and Therapeutic Perspectives in Kidney Transplantation. Front Immunol 2020; 10:3142. [PMID: 32082306 PMCID: PMC7005052 DOI: 10.3389/fimmu.2019.03142] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2019] [Accepted: 12/24/2019] [Indexed: 12/14/2022] Open
Abstract
Recent data from the World Population Prospects projects that, by 2050, nearly all regions in the world will have a quarter or more of the population aged 60 and above. Chronic kidney disease (CKD) has a high global prevalence (~13%) worldwide, and the prevalence of chronic kidney disease and end-stage kidney disease increase with age. Kidney transplantation remains the best therapeutic option for end-stage kidney disease, offering a survival benefit in comparison with dialysis maintenance for most patients. This review focuses on immunological aspects of kidney transplantation in older patients and marginal donors, i.e., 60 years or older deceased kidney donors or 50–59 years old deceased kidney donors with comorbidities. Clinical outcomes of kidney recipients in terms of renal and patient survival are more than acceptable even for patients over 70. In this population, the first cause of graft loss is death with a functional graft. However, the inherent issues of these transplantations are the acceptance or refusal of frail kidney from an old donor and the increased immunogenicity of these organs in balance with potential frail and immunosenescent recipients. Finally, the immunosuppressive regimen itself is a challenge for the future of the transplant, to prevent adverse effects such as nephrotoxicity and higher risk of infections or cancer in a population already at risk. Belatacept may have a good place in the immunosuppressive strategy to improve efficacy and the safety posttransplantation.
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Affiliation(s)
- Johan Noble
- Service de Néphrologie, Hémodialyse, Aphéréses et Transplantation Rénale, Centre Hospitalier Universitaire (CHU) de Grenoble-Alpes, Grenoble, France.,Université Grenoble Alpes, Grenoble, France
| | - Thomas Jouve
- Service de Néphrologie, Hémodialyse, Aphéréses et Transplantation Rénale, Centre Hospitalier Universitaire (CHU) de Grenoble-Alpes, Grenoble, France.,Université Grenoble Alpes, Grenoble, France
| | - Paolo Malvezzi
- Service de Néphrologie, Hémodialyse, Aphéréses et Transplantation Rénale, Centre Hospitalier Universitaire (CHU) de Grenoble-Alpes, Grenoble, France
| | - Caner Süsal
- Collaborative Transplant Study, Institute of Immunology, Heidelberg University, Heidelberg, Germany
| | - Lionel Rostaing
- Service de Néphrologie, Hémodialyse, Aphéréses et Transplantation Rénale, Centre Hospitalier Universitaire (CHU) de Grenoble-Alpes, Grenoble, France.,Université Grenoble Alpes, Grenoble, France
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46
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Echterdiek F, Schwenger V, Döhler B, Latus J, Kitterer D, Heemann U, Süsal C. Kidneys From Elderly Deceased Donors-Is 70 the New 60? Front Immunol 2019; 10:2701. [PMID: 31827468 PMCID: PMC6890834 DOI: 10.3389/fimmu.2019.02701] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 11/04/2019] [Indexed: 01/26/2023] Open
Abstract
There is a growing shortage of kidney donors leading to extended transplant waiting times associated with increased mortality. To expand the donor pool, clinicians nowadays regularly accept organs from elderly donors, including those aged ≥70 years. There is only limited and conflicting data whether kidneys from these elderly donors allow for satisfactory allograft outcome rates. To asses this question, the 5-year death censored graft survival of 116,870 adult first deceased donor kidney allograft recipients that were transplanted at European centers between 1997 and 2016 and reported to the “Collaborative Transplant Study” were analyzed using Kaplan–Meier analysis and country stratified Cox regression. The combinations of the two transplant periods 1997–2006 and 2007–2016 with the donor age categories 18–49, 50–59, 60–69, and ≥70 years were considered. From 1997–2006 to 2007–2016, the median donor age increased from 50 to 55 years and the proportion of kidneys from ≥60-year-old donors rose from 24.1 to 38.8%. At the same time, the proportion of kidneys from ≥70-year-old donors more than doubled (6.7 vs. 15.4%). Between 1997–2006 and 2007–2016, the 5-year graft survival improved in all donor age categories. During 2007–2016, the 5-year death censored graft survival of kidneys from ≥70-year-old donors was comparable to that of kidneys from 60 to 69-year-old donors during 1997–2006. This was true both for younger recipients (18–64 years) and older recipients (≥65 years). Among the younger recipients, 45–64-year-old recipients showed the best death censored graft survival rates for kidneys from old donors. In the country-stratified Cox regression analysis, compared to the reference of grafts from 18 to 49-year-old donors, the hazard ratio for grafts from ≥70-year-old donors during 2007–2016 was 1.92, exactly the same as the hazard ratio for grafts from 60 to 69-year-old donors during 1997–2006. Our analysis indicates that within only one further decade (1997–2006 vs. 2007–2016) the 5-year death censored graft survival of kidneys from ≥70-year old donors improved to the level of kidneys from 60 to 69-year-old donors in the previous decade.
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Affiliation(s)
| | - Vedat Schwenger
- Department of Nephrology, Klinikum Stuttgart, Stuttgart, Germany
| | - Bernd Döhler
- Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany
| | - Joerg Latus
- Department of Nephrology, Klinikum Stuttgart, Stuttgart, Germany
| | - Daniel Kitterer
- Department of Nephrology, Klinikum Stuttgart, Stuttgart, Germany
| | - Uwe Heemann
- Department of Nephrology, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
| | - Caner Süsal
- Institute of Immunology, Heidelberg University Hospital, Heidelberg, Germany
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Long-Term Outcome of Kidney Retransplantation in Comparison With First Transplantation: A Propensity Score Matching Analysis. Transplant Proc 2019; 51:2582-2586. [DOI: 10.1016/j.transproceed.2019.03.070] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Accepted: 03/12/2019] [Indexed: 11/20/2022]
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48
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Validation of the Kidney Donor Profile Index (KDPI) to assess a deceased donor's kidneys' outcome in a European cohort. Sci Rep 2019; 9:11234. [PMID: 31375750 PMCID: PMC6677881 DOI: 10.1038/s41598-019-47772-7] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 07/23/2019] [Indexed: 01/06/2023] Open
Abstract
The Kidney Donor Profile Index (KDPI) was introduced in the United States in 2014 to guide the decision making of clinicians with respect to accepting or declining a donated kidney. To evaluate whether the KDPI can be applied to a European cohort, we retrospectively assessed 580 adult patients who underwent renal transplantation (brain-dead donors) between January 2007 and December 2014 at our center and compared their KDPIs with their short- and long-term outcomes. This led to the observation of two associations: one between the KDPI and the estimated glomerular filtration rate at one year (1-y-eGFR) and the other between the KDPI and the death-censored allograft survival rate (both p < 0.001). Following this, the individual input factors of the KDPI were analyzed to assess their potential to evaluate the quality of a donor organ. We found that a donor’s age alone is significantly predictive in terms of 1-y-eGFR and death-censored allograft survival (both p < 0.001). Therefore, a donor’s age may serve as a simple reference for future graft function. Furthermore, we found that an organ with a low KDPI or from a young donor has an improved graft survival rate whereas kidneys with a high KDPI or from an older donor yield an inferior performance, but they are still acceptable. Therefore, we would not encourage defining a distinct KDPI cut-off in the decision-making process of accepting or declining a kidney graft.
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Pereira LDNG, Nogueira PCK. Non-standard criteria donors in pediatric kidney transplantation. Pediatr Transplant 2019; 23:e13452. [PMID: 31066489 DOI: 10.1111/petr.13452] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Revised: 03/20/2019] [Accepted: 03/22/2019] [Indexed: 12/21/2022]
Abstract
KT remains the treatment of choice for ESRD in children. However, the demand for kidney transplants continues to outstrip supply, even in the pediatric scenario. We reviewed the applicability of nonSCDs for pediatric KT. There is a lack of studies analyzing this modality among pediatric donors and recipients, where most conclusions are based on predictions from adult data. Nevertheless, marginal donors might be a reasonable option in selected cases. For example, the use of older LDs is an acceptable option, with outcomes comparable to SCDs. Organs donated after cardiac death represent another possibility, albeit with logistic, ethical, and legal limitations in some countries. AKI donors also constitute an option in special situations, although there are no pediatric data on these transplants. Likewise, there are no data on the use of expanded criteria donors in pediatric patients, but this appears not to be a good option, considering the compromised long-term survival.
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Affiliation(s)
| | - Paulo Cesar Koch Nogueira
- Pediatric Nephrology Division, Pediatric Department, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
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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: 30] [Impact Index Per Article: 5.0] [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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