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de Necochea Campion R, Pesqueira M, Vallejos P, McCullough C, Bloesch A, LaRosa SP. A lectin affinity plasmapheresis device removes extracellular vesicles and microRNAs from renal perfusates following controlled oxygenated rewarming of discarded donor kidneys. Transpl Immunol 2025; 90:102215. [PMID: 40024312 DOI: 10.1016/j.trim.2025.102215] [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: 11/12/2024] [Revised: 02/26/2025] [Accepted: 02/27/2025] [Indexed: 03/04/2025]
Abstract
Kidney transplantation is considered the benchmark treatment for end-stage kidney disease patients, yet the scarcity of suitable kidneys poses a significant hindrance for patients and healthcare providers. One approach is to extend the criteria for the use of kidneys from deceased brain death and deceased circulatory death donors. Use of these organs, especially from these extended criteria donors, is associated with ischemia reperfusion injury and resultant delayed graft function as well as increased rates of allograft rejection. To lessen these complications as well as increase the time of organ viability assessment, machine perfusion has been evaluated on recovered kidneys. In this study we examined the immunogenic molecular content of perfusates from discarded organs that had undergone Controlled Oxygenated Rewarming (COR). Perfusates were analyzed for extracellular vesicles (EVs), DNA (Deoxyribonucleic acid), and microRNAs. These perfusates were then pumped over a plasma separator containing a lectin affinity resin. Following treatment, a significant diminution in extracellular vesicles, dsDNA (double-stranded DNA) associated with EVs, and microRNAs (miRNA) were observed. Specifically, in three out of the four renal perfusates analyzed there was significant removal of small EVs (<200 nm) and vesicles loaded with dsDNA (p < 0.05). Notably, depletion of larger EVs (100-500 nm) was found to be significant in all treated perfusates (p < 0.01). NanoString analysis of miRNA found 5 species potentially involved in renal dysfunction (hsa-let 7a-5p, hsa-miR-148b-3p, hsa-miR-148a-3p, hsa-miR-29b-3pb and hsa-miR-99a5p) to be significantly depleted in treated renal perfusates (p ≤ 0.05). These results support a future study incorporating this treatment method into a dynamic machine perfusion circuit to explore if reduction of these mediators is associated with improved function of retrieved kidneys.
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Affiliation(s)
| | - Miguel Pesqueira
- Aethlon Medical Inc., 11555 Sorrento Valley Rd., San Diego, CA, United States of America
| | - Paul Vallejos
- Aethlon Medical Inc., 11555 Sorrento Valley Rd., San Diego, CA, United States of America
| | - Cameron McCullough
- Aethlon Medical Inc., 11555 Sorrento Valley Rd., San Diego, CA, United States of America
| | - Alessio Bloesch
- Aethlon Medical Inc., 11555 Sorrento Valley Rd., San Diego, CA, United States of America
| | - Steven P LaRosa
- Aethlon Medical Inc., 11555 Sorrento Valley Rd., San Diego, CA, United States of America
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Duarte S, Fassler AM, Willman M, Lewis D, Warren C, Angeli-Pahim I, Shah R, Vrakas G, El Hinnawi A, De Faria W, Beduschi T, Battula N, Zarrinpar A. Soluble DNA Concentration in the Perfusate is a Predictor of Posttransplant Renal Function in Hypothermic Machine Perfused Kidney Allografts. Transplant Direct 2025; 11:e1768. [PMID: 40124244 PMCID: PMC11927653 DOI: 10.1097/txd.0000000000001768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 12/19/2024] [Indexed: 03/25/2025] Open
Abstract
Background Hypothermic machine perfusion (HMP) has greatly improved kidney allograft preservation. However, tissue damage still occurs during HMP, affecting posttransplant graft function. Therefore, better methods are needed to continuously assess organ quality and to predict posttransplant graft function and survival. We propose that soluble DNA (sDNA) concentration in HMP perfusate can be used as a noninvasive biomarker for this purpose. Methods Perfusate samples of kidney grafts placed on HMP were collected 5 min after the initiation of HMP and again at the conclusion of HMP. sDNA of nuclear origin from the perfusate was quantified by real-time polymerase chain reaction and correlated with HMP parameters and posttransplant clinical outcomes. Results Kidney grafts from 52 deceased donors placed on HMP were studied. Perfusate sDNA concentration was significantly higher in transplanted kidneys with delayed graft function. Higher concentrations of perfusate sDNA at 5 min and at HMP conclusion were also correlated with lower graft function in the initial posttransplant period, as measured by postoperative day 2, 3, and 4 creatinine reduction ratios. Standard pump parameters such as renal vascular resistance and renal vascular flow were poor indicators of early posttransplant graft function. Conclusions sDNA concentration in HMP perfusate of kidney grafts can indicate the quality of kidney graft preservation and predict posttransplant renal function. This biomarker should be explored further to improve renal organ assessment and transplantation outcomes.
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Affiliation(s)
- Sergio Duarte
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Anne-Marie Fassler
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Matthew Willman
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Duncan Lewis
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Curtis Warren
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Isabella Angeli-Pahim
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Rushi Shah
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Georgios Vrakas
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Ashraf El Hinnawi
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Werviston De Faria
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Thiago Beduschi
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
| | - Narendra Battula
- Division of Transplant Surgery, Department of Surgery, Oklahoma University College of Medicine, Oklahoma City, OK
| | - Ali Zarrinpar
- Division of Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Florida College of Medicine, Gainesville, FL
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Kujawa-Szewieczek A, Słabiak-Błaż N, Kolonko A, Więcek A, Piecha G. Kidney Donor Risk Index and Cardiovascular Complications in a Long-Term Follow-Up Observation. J Clin Med 2025; 14:2346. [PMID: 40217795 PMCID: PMC11989476 DOI: 10.3390/jcm14072346] [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: 12/09/2024] [Revised: 03/04/2025] [Accepted: 03/22/2025] [Indexed: 04/14/2025] Open
Abstract
Background: The suitability of the Kidney Donor Risk Index (KDRI) has not been fully validated in the European population. The aim of this study was to evaluate the value of the KDRI in predicting kidney graft function and cardiovascular events (CVEs) in a Polish cohort of kidney transplant recipients (KTRs). Methods: In this retrospective study kidney graft function and CVEs were analyzed among 1420 patients transplanted between 1999 and 2017 and followed until 2021. The KDRI was calculated according to the formula proposed by Rao. Patients were assigned into quartiles (Qs) of KDRI values. Results: Patients in Q4 were older, with higher BMI, longer cold ischemia time (CIT), and a greater rate of ischemic heart disease at the transplantation. The KDRI value determined both early and long-term graft function. During a median follow-up period of 91 months, at least one cardiovascular event was noted in 227 (16.0%) kidney transplant recipients. There was a significant increasing trend for the occurrence of post-transplant CV complications along the consecutive KDRI quartiles (χ2 = 7.3; p < 0.01) among kidney transplant patients younger than 50 years at the time of transplantation. Conclusions: The KDRI is an adequate prognostic tool also for the European population. Despite the KDRI not being used for allocation in Poland we found that kidneys with a higher KDRI are allocated to recipients with worse survival prognosis. The quality of kidneys from a deceased donor may be related to the occurrence of post-transplant cardiovascular complications in recipients younger than 50 years at the transplantation, including those without history of comorbidities such as diabetes or cardiovascular disease.
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Affiliation(s)
- Agata Kujawa-Szewieczek
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Francuska 20/24, 40-027 Katowice, Poland; (N.S.-B.); (A.K.); (A.W.); (G.P.)
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Kolesnyk M, Stepanova N, Korol L, Shifris I, Zograbian R, Voronyak O. Неімуноопосередковані детермінанти тривалості функціонування трансплантованої нирки. UKRAINIAN JOURNAL OF NEPHROLOGY AND DIALYSIS 2025:81-96. [DOI: 10.31450/ukrjnd.1(85).2025.10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2025]
Abstract
Незважаючи на успіхи щодо подовження тривалості функціонування трансплантованої нирки, вона складає, у середньому, лише 10-12 років. При цьому тривалість функціонування трансплантованої нирки прогресивно знижується вже після першого року трансплантації. Прогресуюче зниження функціональної здатності трансплантованої нирки обумовлюється двома основними групами причин: неімуноопосередкованими та імуноопосередкованими.
Відстрочена функція трансплантата (ВФТ) є кількісним і якісним інтегральним проявом як імуноопосередкованих так і неімуноопосередкованих механізмів, котра суттєво впливає на короткострокові та довгострокові результати трансплантації. Питома вага кожної складової у конкретного реципієнта індивідуальна і змінюється протягом усього післятрансплантаційного періоду. Робіт, присвячених визначенню неімуноопосередкованих детермінант тривалості функціонування трансплантату загалом і виникнення ВФТ у тому числі, небагато. У цьому огляді систематизовані ключові неімуноопосередковані детермінанти як можливі терапевтичні мішені, що є визначальним для своєчасного початку лікування та подовження терміну функціонування трансплантованої нирки.
Очевидно, що на сьогодні максимального результату щодо тривалості функціонування трансплантованої нирки можна досягти встановивши терапевтичні мішені та ефективні способи впливу на імуно та неімуноопосередковані складові як донора так і реціпієнта.
Мета аналітичного огляду – визначити неімуноопосередковані детермінанти ретро та проспективне вивчення яких дозволить запропонувати терапевтичні мішені для подовження функціонування трансплантованої нирки.
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Woo HY, An JM, Park MY, Han A, Kim Y, Kang J, Ahn S, Min SK, Ha J, Kim D, Min S. Cysteine as an Innovative Biomarker for Kidney Injury. Transplantation 2025; 109:309-318. [PMID: 39049125 DOI: 10.1097/tp.0000000000005138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2024]
Abstract
BACKGROUND Kidney transplantation is a widely used treatment for end-stage kidney disease. Nevertheless, the incidence of acute kidney injury (AKI) in deceased donors poses a potential hazard because it significantly increases the risk of delayed graft function and potentially exerts an influence on the kidney allograft outcome. It is crucial to develop a diagnostic model capable of assessing the existence and severity of AKI in renal grafts. However, no suitable kidney injury markers have been developed thus far. METHODS We evaluated the efficacy of the molecular probe NPO-B, which selectively responds to cysteine, as a new diagnostic tool for kidney injury. We used an in vitro model using ischemia/reperfusion injury human kidney-2 cells and an in vivo ischemia/reperfusion injury mouse model. Additionally, cysteine was investigated using urine samples from deceased donors and living donors to assess the applicability of detection techniques to humans. RESULTS This study confirmed that the NPO-B probe effectively identified and visualized the severity of kidney injury by detecting cysteine in both in vitro and in vivo models. We observed that the fluorescence intensity of urine samples measured using NPO-B from the deceased donors who are at a high risk of renal injury was significantly stronger than that of the living donors. CONCLUSIONS If implemented in clinical practice, this new diagnostic tool using NPO-B can potentially enhance the success rate of kidney transplantation by accurately determining the extent of AKI in renal grafts.
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Affiliation(s)
- Hye Young Woo
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jong Min An
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Min Young Park
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ahram Han
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Youngwoong Kim
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Jisoo Kang
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Sanghyun Ahn
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Seung-Kee Min
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jongwon Ha
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Dokyoung Kim
- Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Republic of Korea
- Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Core Research Institute (CRI), Kyung Hee University, Seoul, Republic of Korea
- Department of Anatomy and Neurobiology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea
- Center for Converging Humanities, Kyung Hee University, Seoul, Republic of Korea
- KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, Republic of Korea
- UC San Diego Materials Research Science and Engineering Center, La Jolla, CA
- Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Republic of Korea
- Department of Precision Medicine, Graduate School, Kyung Hee University, Seoul, Republic of Korea
| | - Sangil Min
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
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Klein Nulend R, Hameed A, Singla A, Yuen L, Lee T, Yoon P, Nahm C, Wong G, Laurence J, Lim WH, Hawthorne WJ, Pleass H. Normothermic Machine Perfusion and Normothermic Regional Perfusion of DCD Kidneys Before Transplantation: A Systematic Review. Transplantation 2025; 109:362-375. [PMID: 39020460 DOI: 10.1097/tp.0000000000005132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/19/2024]
Abstract
BACKGROUND To overcome organ shortages, donation after circulatory death (DCD) kidneys are being increasingly used for transplantation. Prior research suggests that DCD kidneys have inferior outcomes compared with kidneys donated after brain death. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) may enhance the preservation of DCD kidneys and improve transplant outcomes. This study aimed to review the evidence surrounding NMP and NRP in DCD kidney transplantation. METHODS Two independent reviewers conducted searches for all publications reporting outcomes for NMP and NRP-controlled DCD kidneys, focusing on delayed graft function, primary nonfunction, graft function, graft survival, and graft utilization. Weighted means were calculated for all relevant outcomes and controls. Formal meta-analyses could not be conducted because of significant heterogeneity. RESULTS Twenty studies were included for review (6 NMP studies and 14 NRP studies). Delayed graft function rates seemed to be lower for NRP kidneys (24.6%) compared with NMP kidneys (54.3%). Both modalities yielded similar outcomes with respect to primary nonfunction (NMP 3.3% and NRP 5.6%), graft function (12-mo creatinine 149.3 μmol/L for NMP and 129.9 μmol/L for NRP), and graft utilization (NMP 83.3% and NRP 89%). Although no direct comparisons exist, our evidence suggests that both modalities have good short- and medium-term graft outcomes and high graft survival rates. CONCLUSIONS Current literature demonstrates that both NMP and NRP are feasible strategies that may increase donor organ utilization while maintaining acceptable transplant outcomes and likely improved outcomes compared with cold-stored DCD kidneys. Further research is needed to directly compare NRP and NMP outcomes.
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Affiliation(s)
| | - Ahmer Hameed
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Animesh Singla
- Westmead Institute for Medical Research, Westmead, NSW, Australia
| | - Lawrence Yuen
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
| | - Taina Lee
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
| | - Peter Yoon
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
| | - Chris Nahm
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
| | - Germaine Wong
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
| | - Jerome Laurence
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
- RPA Institute of Academic Surgery, University of Sydney, Sydney, NSW, Australia
| | - Wai H Lim
- Faculty of Medicine, University of Western Australia, Crawley, WA, Australia
| | - Wayne J Hawthorne
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
- Westmead Institute for Medical Research, Westmead, NSW, Australia
| | - Henry Pleass
- Department of Surgery, Westmead Hospital, Westmead, NSW, Australia
- Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
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Ciesielski W, Frąk W, Gmitrzuk J, Kuczyński P, Klimczak T, Durczyński A, Strzelczyk J, Hogendorf P. The assesement of the long-term effects of kidney transplantation, including the incidence of malignant tumors, in recipients operated on between 2006 and 2015 - a cohort study and literature review. POLISH JOURNAL OF SURGERY 2025; 97:1-9. [PMID: 40247787 DOI: 10.5604/01.3001.0054.9677] [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] [Indexed: 04/19/2025]
Abstract
<b>Introduction:</b> Chronic kidney disease (CKD) is a global public health problem, occurring more frequently in developed countries. In Poland, it affects approximately 4 million people, which constitutes 10.8% of the population. End-stage renal disease (ESRD) requires renal replacement therapy - dialysis therapy or kidney transplantation. Kidney transplantation, supported by immunosuppressive therapy, is the preferred method of treating ESRD, improving the quality and length of life of patients.<b>Aim and Methods:</b> The aim of the study was to determine the long-term effects of kidney transplantation, including proper graft function, the frequency of adverse effects of immunosuppressive therapy, the degree of patient compliance with therapeutic recommendations, and the incidence of malignancies. A survey was conducted in a group of 137 patients who underwent kidney transplantation between 2006 and 2015. Hospitalization data were also analyzed, including age, body weight and blood type of the recipient.<b>Results:</b> Of the 137 patients studied, 61 were women and 76 were men. The mean age of the patients was 45.1 years. The most common etiology of CKD was glomerulonephritis. After kidney transplantation, 86.86% of patients declared normal graft function. Post-transplant weight gain was noted in 75.18% of patients. 11.68% of recipients developed malignancies, with an average time from transplantation to diagnosis of 5.1 years. Of the patients with cancer, 93.75% maintained normal graft function.<b>Conclusions:</b> Long-term effects of kidney transplantation are satisfactory, with a high percentage of patients maintaining normal graft function. Complications associated with immunosuppressive therapy are comparable to literature data. It is necessary to increase patient awareness of modifiable risk factors to improve treatment outcomes. The incidence of malignancy after transplantation is lower than in the literature, but the methodological limitations of the study must be taken into account. Cancer treatment had no significant effect on graft function in most cases.
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Affiliation(s)
- Wojciech Ciesielski
- Department of General and Transplant Surgery, Medical University of Lodz, Poland
| | - Weronika Frąk
- Student Scientific Circle at the Department of General and Transplant Surgery of the Medical University of Lodz, Poland
| | - Julita Gmitrzuk
- Student Scientific Circle at the Department of General and Transplant Surgery of the Medical University of Lodz, Poland
| | - Piotr Kuczyński
- Student Scientific Circle at the Department of General and Transplant Surgery of the Medical University of Lodz, Poland
| | - Tomasz Klimczak
- Department of General and Transplant Surgery, Medical University of Lodz, Poland
| | - Adam Durczyński
- Department of General and Transplant Surgery, Medical University of Lodz, Poland
| | - Janusz Strzelczyk
- Department of General and Transplant Surgery, Medical University of Lodz, Poland
| | - Piotr Hogendorf
- Department of General and Transplant Surgery, Medical University of Lodz, Poland
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Amantéa RP, Olsen VDR, Hastenteufel LCT, Borges FK, Manfro RC, Goldraich LA, Clausell N. Predictive Value of Cardiac Biomarkers on Delayed Graft Function in Renal Transplant Patients. Arq Bras Cardiol 2024; 121:e20230858. [PMID: 39607168 PMCID: PMC11634288 DOI: 10.36660/abc.20230858] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 08/01/2024] [Accepted: 09/04/2024] [Indexed: 11/29/2024] Open
Affiliation(s)
- Rodrigo Pinheiro Amantéa
- Hospital de Clínicas de Porto AlegrePorto AlegreRSBrasilHospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, RS – Brasil
| | - Virgílio da Rocha Olsen
- Santa Casa de Misericórdia de Porto AlegrePorto AlegreRSBrasilSanta Casa de Misericórdia de Porto Alegre, Porto Alegre, RS – Brasil
| | | | - Flávia K. Borges
- McMaster UniversityHamiltonOntarioCanadáMcMaster University, Hamilton, Ontario – Canadá
| | - Roberto Ceratti Manfro
- Hospital de Clínicas de Porto AlegrePorto AlegreRSBrasilHospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, RS – Brasil
| | - Lívia Adams Goldraich
- Hospital de Clínicas de Porto AlegrePorto AlegreRSBrasilHospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, RS – Brasil
| | - Nadine Clausell
- Hospital de Clínicas de Porto AlegrePorto AlegreRSBrasilHospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, RS – Brasil
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Ma X, Moradi M, Ma X, Tang Q, Levi M, Chen Y, Zhang HK. Large area kidney imaging for pre-transplant evaluation using real-time robotic optical coherence tomography. COMMUNICATIONS ENGINEERING 2024; 3:122. [PMID: 39223332 PMCID: PMC11368928 DOI: 10.1038/s44172-024-00264-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Accepted: 08/07/2024] [Indexed: 09/04/2024]
Abstract
Optical coherence tomography (OCT) can be used to image microstructures of human kidneys. However, current OCT probes exhibit inadequate field-of-view, leading to potentially biased kidney assessment. Here we present a robotic OCT system where the probe is integrated to a robot manipulator, enabling wider area (covers an area of 106.39 mm by 37.70 mm) spatially-resolved imaging. Our system comprehensively scans the kidney surface at the optimal altitude with preoperative path planning and OCT image-based feedback control scheme. It further parameterizes and visualizes microstructures of large area. We verified the system positioning accuracy on a phantom as 0.0762 ± 0.0727 mm and showed the clinical feasibility by scanning ex vivo kidneys. The parameterization reveals vasculatures beneath the kidney surface. Quantification on the proximal convoluted tubule of a human kidney yields clinical-relevant information. The system promises to assess kidney viability for transplantation after collecting a vast amount of whole-organ parameterization and patient outcomes data.
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Affiliation(s)
- Xihan Ma
- Department of Robotics Engineering, Worcester Polytechnic Institute, Worcester, MA, USA
| | - Mousa Moradi
- Department of Biomedical Engineering, University of Massachusetts, Amherst, MA, USA
| | - Xiaoyu Ma
- Department of Biomedical Engineering, University of Massachusetts, Amherst, MA, USA
| | - Qinggong Tang
- The Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK, USA
| | - Moshe Levi
- Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC, USA
| | - Yu Chen
- Department of Biomedical Engineering, University of Massachusetts, Amherst, MA, USA.
- College of Photonic and Electronic Engineering, Fujian Normal University, Fuzhou, Fujian, PR China.
| | - Haichong K Zhang
- Department of Robotics Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
- Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, MA, USA.
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Rodriguez-Sanchez E, Aceves-Ripoll J, Mercado-García E, Navarro-García JA, Andrés A, Aguado JM, Segura J, Ruilope LM, Fernández-Ruiz M, Ruiz-Hurtado G. Donor-Dependent Variations in Systemic Oxidative Stress and Their Association with One-Year Graft Outcomes in Kidney Transplantation. Am J Nephrol 2024; 55:509-519. [PMID: 38857579 DOI: 10.1159/000539509] [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: 03/22/2024] [Accepted: 05/20/2024] [Indexed: 06/12/2024]
Abstract
INTRODUCTION Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear. METHODS We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months. Oxidative status was determined using OxyScore and AntioxyScore indexes, which comprise several circulating biomarkers of oxidative damage and antioxidant defense. Donor types included donation after brain death (DBD [61.0%]), donation after circulatory death (DCD [26.8%]), and living donation (LD [12.1%]). RESULTS There was an overall increase in oxidative damage early after transplantation, which was significantly higher in DCD as compared to DBD and LD recipients. The multivariate adjustment confirmed the independent association of OxyScore and type of deceased donation with DGF, donor kidney function, and induction therapy with antithymocyte globulin. There were no differences in terms of antioxidant defense. Lower oxidative damage at day 7 predicted better graft function at 1-year posttransplant only in DBD recipients. CONCLUSION DCD induced greater short-term oxidative damage after KT, whereas the early levels of oxidative damage were predictive of the graft function 1 year after KT among DBD recipients.
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Affiliation(s)
- Elena Rodriguez-Sanchez
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Jennifer Aceves-Ripoll
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Elisa Mercado-García
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - José A Navarro-García
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Amado Andrés
- Department of Nephrology, Hospital Universitario "12 de Octubre", Research Institute Hospital "12 de Octubre" (Imas12), Madrid, Spain
- School of Medicine, Universidad Complutense, Madrid, Spain
| | - José M Aguado
- School of Medicine, Universidad Complutense, Madrid, Spain
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Research Institute Hospital "12 de Octubre" (Imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Julián Segura
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
| | - Luis M Ruilope
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, Madrid, Spain
- European University of Madrid, Madrid, Spain
| | - Mario Fernández-Ruiz
- School of Medicine, Universidad Complutense, Madrid, Spain
- Unit of Infectious Diseases, Hospital Universitario "12 de Octubre", Research Institute Hospital "12 de Octubre" (Imas12), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Gema Ruiz-Hurtado
- Cardiorenal Translational Laboratory and Hypertension Unit, Research Institute Hospital "12 de Octubre" (Imas12), Hospital Universitario "12 de Octubre", Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBER-CV), Instituto de Salud Carlos III, Madrid, Spain
- Department of Physiology, School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
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11
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Bamforth RJ, Trachtenberg A, Ho J, Wiebe C, Ferguson TW, Rigatto C, Forget E, Dodd N, Tangri N. Expanding Access to High KDPI Kidney Transplant for Recipients Aged 60 y and Older: Cost Utility and Survival. Transplant Direct 2024; 10:e1629. [PMID: 38757046 PMCID: PMC11098249 DOI: 10.1097/txd.0000000000001629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2023] [Revised: 02/05/2024] [Accepted: 02/21/2024] [Indexed: 05/18/2024] Open
Abstract
Background Modern organ allocation systems are tasked with equitably maximizing the utility of transplanted organs. Increasing the use of deceased donor organs at risk of discard may be a cost-effective strategy to improve overall transplant benefit. We determined the survival implications and cost utility of increasing the use of marginal kidneys in an older adult Canadian population of patients with end-stage kidney disease. Methods We constructed a cost-utility model with microsimulation from the perspective of the Canadian single-payer health system for incident transplant waitlisted patients aged 60 y and older. A kidney donor profile index score of ≥86 was considered a marginal kidney. Donor- and recipient-level characteristics encompassed in the kidney donor profile index and estimated posttransplant survival scores were used to derive survival posttransplant. Patients were followed up for 10 y from the date of waitlist initiation. Our analysis compared the routine use of marginal kidneys (marginal kidney scenario) with the current practice of limited use (status quo scenario). Results The 10-y mean cost and quality-adjusted life-years per patient in the marginal kidney scenario were estimated at $379 485.33 (SD: $156 872.49) and 4.77 (SD: 1.87). In the status quo scenario, the mean cost and quality-adjusted life-years per patient were $402 937.68 (SD: $168 508.85) and 4.37 (SD: 1.87); thus, the intervention was considered dominant. At 10 y, 62.8% and 57.0% of the respective cohorts in the marginal kidney and status quo scenarios remained alive. Conclusions Increasing the use of marginal kidneys in patients with end-stage kidney disease aged 60 y and older may offer cost savings, improved quality of life, and greater patient survival in comparison with usual care.
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Affiliation(s)
- Ryan J. Bamforth
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, MB, Canada
| | - Aaron Trachtenberg
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
- Transplant Manitoba Adult Kidney Program, Winnipeg, MB, Canada
| | - Julie Ho
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
- Transplant Manitoba Adult Kidney Program, Winnipeg, MB, Canada
| | - Chris Wiebe
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
- Transplant Manitoba Adult Kidney Program, Winnipeg, MB, Canada
| | - Thomas W. Ferguson
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, MB, Canada
| | - Claudio Rigatto
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, MB, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
| | - Evelyn Forget
- Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
| | - Nancy Dodd
- Transplant Manitoba Adult Kidney Program, Winnipeg, MB, Canada
| | - Navdeep Tangri
- Chronic Disease Innovation Centre, Seven Oaks General Hospital, Winnipeg, MB, Canada
- Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada
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12
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Diamond JM, Anderson MR, Cantu E, Clausen ES, Shashaty MGS, Kalman L, Oyster M, Crespo MM, Bermudez CA, Benvenuto L, Palmer SM, Snyder LD, Hartwig MG, Wille K, Hage C, McDyer JF, Merlo CA, Shah PD, Orens JB, Dhillon GS, Lama VN, Patel MG, Singer JP, Hachem RR, Michelson AP, Hsu J, Russell Localio A, Christie JD. Development and validation of primary graft dysfunction predictive algorithm for lung transplant candidates. J Heart Lung Transplant 2024; 43:633-641. [PMID: 38065239 PMCID: PMC10947904 DOI: 10.1016/j.healun.2023.11.019] [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: 03/14/2023] [Revised: 11/05/2023] [Accepted: 11/30/2023] [Indexed: 03/18/2024] Open
Abstract
BACKGROUND Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Accurate prediction of PGD risk could inform donor approaches and perioperative care planning. We sought to develop a clinically useful, generalizable PGD prediction model to aid in transplant decision-making. METHODS We derived a predictive model in a prospective cohort study of subjects from 2012 to 2018, followed by a single-center external validation. We used regularized (lasso) logistic regression to evaluate the predictive ability of clinically available PGD predictors and developed a user interface for clinical application. Using decision curve analysis, we quantified the net benefit of the model across a range of PGD risk thresholds and assessed model calibration and discrimination. RESULTS The PGD predictive model included distance from donor hospital to recipient transplant center, recipient age, predicted total lung capacity, lung allocation score (LAS), body mass index, pulmonary artery mean pressure, sex, and indication for transplant; donor age, sex, mechanism of death, and donor smoking status; and interaction terms for LAS and donor distance. The interface allows for real-time assessment of PGD risk for any donor/recipient combination. The model offers decision-making net benefit in the PGD risk range of 10% to 75% in the derivation centers and 2% to 10% in the validation cohort, a range incorporating the incidence in that cohort. CONCLUSION We developed a clinically useful PGD predictive algorithm across a range of PGD risk thresholds to support transplant decision-making, posttransplant care, and enrich samples for PGD treatment trials.
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Affiliation(s)
- Joshua M Diamond
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
| | - Michaela R Anderson
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Edward Cantu
- Division of Cardiovascular Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Emily S Clausen
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michael G S Shashaty
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Laurel Kalman
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Michelle Oyster
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Maria M Crespo
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Christian A Bermudez
- Division of Cardiovascular Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Luke Benvenuto
- Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University School of Medicine, New York, New York
| | - Scott M Palmer
- Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina
| | - Laurie D Snyder
- Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina
| | - Matthew G Hartwig
- Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Duke University Medical Center, Durham, North Carolina
| | - Keith Wille
- Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama
| | - Chadi Hage
- Division of Pulmonary, Allergy, and Critical Care, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - John F McDyer
- Division of Pulmonary, Allergy, and Critical Care, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Christian A Merlo
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University Medical Center, Baltimore, Maryland
| | - Pali D Shah
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University Medical Center, Baltimore, Maryland
| | - Jonathan B Orens
- Division of Pulmonary and Critical Care Medicine, Johns Hopkins University Medical Center, Baltimore, Maryland
| | - Ghundeep S Dhillon
- Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, Palo Alto, California
| | - Vibha N Lama
- Division of Pulmonary and Critical Care Medicine, University of Michigan Medical Center, Ann Arbor, Michigan
| | - Mrunal G Patel
- Division of Pulmonary and Critical Care Medicine, Indiana University School of Medicine, Indianapolis, Indiana
| | - Jonathan P Singer
- Division of Pulmonary and Critical Care Allergy and Sleep Medicine, University of California, San Francisco, San Francisco, California
| | - Ramsey R Hachem
- Division of Pulmonary and Critical Care Medicine, Washington University, St. Louis, Missouri
| | - Andrew P Michelson
- Division of Pulmonary and Critical Care Medicine, Washington University, St. Louis, Missouri
| | - Jesse Hsu
- Division of Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - A Russell Localio
- Division of Biostatistics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Jason D Christie
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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13
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Ahlmark A, Sallinen V, Eerola V, Lempinen M, Helanterä I. Characteristics of Delayed Graft Function and Long-Term Outcomes After Kidney Transplantation From Brain-Dead Donors: A Single-Center and Multicenter Registry-Based Retrospective Study. Transpl Int 2024; 37:12309. [PMID: 38495816 PMCID: PMC10942003 DOI: 10.3389/ti.2024.12309] [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: 10/26/2023] [Accepted: 02/19/2024] [Indexed: 03/19/2024]
Abstract
Delayed graft function (DGF) after kidney transplantation is common and associated with worse graft outcomes. However, little is known about factors affecting graft survival post-DGF. We studied the association of cold ischemia time (CIT) and Kidney Donor Profile Index (KDPI) with the long-term outcomes of deceased brain-dead donor kidneys with and without DGF. Data from Finland (n = 2,637) and from the US Scientific Registry of Transplant Recipients (SRTR) registry (n = 61,405) was used. The association of KDPI and CIT with the graft survival of kidneys with or without DGF was studied using multivariable models. 849 (32%) kidneys had DGF in the Finnish cohort. DGF and KDPI were independent risk factors for graft loss, [HR 1.32 (95% CI 1.14-1.53), p < 0.001, and HR 1.01 per one point (95% CI 1.01-1.01), p < 0.001, respectively], but CIT was not, [HR 1.00 per CIT hour (95% CI 0.99-1.02), p = 0.84]. The association of DGF remained similar regardless of CIT and KDPI. The US cohort had similar results, but the association of DGF was stronger with higher KDPI. In conclusion, DGF and KDPI, but not CIT, are independently associated with graft survival. The association of DGF with worse graft survival is consistent across different CITs but stronger among marginal donors.
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Affiliation(s)
- Amanda Ahlmark
- Department of Transplantation and Liver Surgery, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
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14
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Okumura K, Dhand A, Misawa R, Sogawa H, Veillette G, Nishida S. The Effect of New Acuity Circle Policy on Simultaneous Liver and Kidney Transplantation in the United States. J Clin Exp Hepatol 2024; 14:101296. [PMID: 38544764 PMCID: PMC10964071 DOI: 10.1016/j.jceh.2023.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2023] [Accepted: 10/17/2023] [Indexed: 03/03/2025] Open
Abstract
Background New deceased donor liver allocation policy using an acuity circle (AC)-based model was implemented on February 4th, 2020. The effect of AC policy on simultaneous liver-kidney transplantation (SLKT) remains unknown. The aim of this study was to assess the effect of AC policy on SLKT waitlist mortality, transplant probability, and post-transplant outcomes. Methods Using the United Network for Organ Sharing database, 4908 adult SLKT candidates during two study periods, pre-AC (Aug-2017 to Feb-2020, N = 2770) and post-AC (Feb-2020 to Dec-2021, N = 2138) were analyzed. Outcomes included 90-day waitlist mortality, transplant probability, and post-transplant patient and graft survival. Results Compared to pre-AC period, SLKT recipients during post-AC period had higher median model for end-stage liver disease (MELD) score (24 vs 23, P < 0.001), and less percentage of MELD exception (4.6% vs 7.7%, P = 0.001). The 90-day waitlist mortality was same, but the probability of SLKT increased in post-AC period (P < 0.001). Post-AC period also saw increased utilization of donation after cardiac death organs (11% vs 6.4%, P < 0.001) and decreased rates of transplantation among Black candidates (7.9% vs 13%). After risk adjustment, post-AC period was not associated with any significant difference in 90-day waitlist mortality (sub-distribution hazard ratio [sHR] 0.80; 95% CI 0.56-1.16, P = 0.24), and a higher 90-day probability of SLKT (sHR 1.68; 95% CI 1.41-1.99, P < 0.001). During post-transplant period, one-year patient survival, liver and kidney graft survival were comparable between two study periods. Conclusions The AC liver allocation policy was associated with increased transplant probability of adult SLKT candidates without decreasing waitlist mortality, post-transplant patient survival, or liver and kidney graft survival.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Abhay Dhand
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Ryosuke Misawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Hiroshi Sogawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Gregory Veillette
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
| | - Seigo Nishida
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, NY, USA
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15
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Pilichowska E, Ostrowski P, Sieńko J. The Impact of Hematological Indices on the Occurrence of Delayed Graft Function (DGF) of Transplanted Kidney. J Clin Med 2023; 12:7514. [PMID: 38137583 PMCID: PMC10744293 DOI: 10.3390/jcm12247514] [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: 10/29/2023] [Revised: 11/25/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND to analyse the effect of haematological indices on the occurrence of Delayed Graft Function (DGF) in patients undergoing kidney transplantation and on the function of the transplanted kidney on the 7th postoperative day. METHODS 365 recipients who underwent kidney transplantation from a donor with known brain death between 2010 and 2017 were included in this retrospective study. Information from patient medical records, donor medical records, and donation and transplantation protocols was used for analysis. Statistica 13 was used for statistical analysis. RESULTS In the study group, DGF occurred in 144 recipients (39.45%), and Non-Graft Function (NGF) occurred in 12 recipients (3.29%). Recipients who developed DGF had a significantly higher Neutrophil/Monocyte Ratio (NMR) before renal transplantation (p = 0.048), a lower NMR value on postoperative day 1 (p < 0.001), and a difference between the values on day 1 and before surgery (p < 0.001). In addition, they had a significantly lower Lymphocyte/Monocyte Ratio (LMR) on postoperative day 1 LMR 1 (p < 0.001). It was shown that the value of the indices based on the ROC curve-NMR1 > 29.29, NMR1-0 > 22.71, and LMR1 > 1.74 (respectively: AUC = 0.624; 95% CI 0.566-0.682; and p < 0.001/AUC = 0.622; 95% CI 0.563-0.680; and p < 0.001/AUC = 0.610; 95% CI 0.550-0.670; and p < 0.001)-can be used to identify recipients with a significant probability of DGF. CONCLUSIONS the NMR and LMR parameters on the first postoperative day and the difference between the NMR values on the first post-transplant day and the first pre-transplant day are predictive factors associated with the risk of DGF.
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Affiliation(s)
- Ewa Pilichowska
- Department of General Surgery and Transplantation, Pomeranian Medical University, 70-111 Szczecin, Poland
| | - Piotr Ostrowski
- Department of Nursing, Pomeranian Medical University, Żołnierska 48, 71-210 Szczecin, Poland
| | - Jerzy Sieńko
- Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland;
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16
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Christianson A, Kaul H, Parsikia A, Chandolias N, Khanmoradi K, Zaki R. Delayed Graft Function in Kidney Retransplantation: United Network for Organ Sharing Data With Linked Primary and Retransplant. J Surg Res 2023; 292:289-296. [PMID: 37678109 DOI: 10.1016/j.jss.2023.07.033] [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: 12/01/2022] [Revised: 06/21/2023] [Accepted: 07/14/2023] [Indexed: 09/09/2023]
Abstract
INTRODUCTION There are several articles exploring the risk factors for primary delayed graft function (DGF). However, current literature does not include many resources on the risk factors for DGF when it is a recipient's second kidney transplant or look at short-term graft and patient survival of DGF retransplants. METHODS United Network for Organ Sharing data from January 2008 to June 2021 were analyzed. Pancreas transplants, multi-organ transplants, and lost to follow-up transplants were excluded. Second transplant patients with DGF were identified. Multivariate logistic regression models based on the primary and second transplant characteristics were created. Survival analysis was performed with Kaplan-Meier methodology and assessed with log-rank test. RESULTS A total of 2964 second kidney transplants were identified. Rate of DGF in the second transplant was 28.4% (843/2964) and 49.2% of them had a prior DGF in their first transplant (P < 0.001). Multivariate analysis confirmed that occurrence of DGF (odds ratio [OR] 1.5, P < 0.001) and graft loss due to acute rejection (OR 1.2, P < 0.005) in the primary transplant were predictors of reappearing DGF in the second transplant. Dialysis at transplant was the greatest risk factor from the second transplant (OR 3.539, P < 0.001). There was a decreased graft survival after 12 mo (77% versus 49% with log t-test <0.001) in the second transplant. However, DGF was not significantly associated with patient survival. CONCLUSIONS This study shows the interaction between primary and second transplant in developing DGF. Survival analysis shows lower graft survival for retransplants in the case of DGF. This study opens the possibility of identifying additional risk factors for patients undergoing retransplant surgeries.
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Affiliation(s)
- Alex Christianson
- Philadelphia College of Osteopathic Medicine - Georgia Campus, Suwanee, Georgia
| | - Hitesh Kaul
- Department of Surgery, Jefferson Einstein Hospital, Philadelphia, Pennsylvania
| | - Afshin Parsikia
- Department of Surgery, Jefferson Einstein Hospital, Philadelphia, Pennsylvania
| | - Nikolaos Chandolias
- Department of Surgery, Jefferson Einstein Hospital, Philadelphia, Pennsylvania
| | - Kamran Khanmoradi
- Department of Surgery, Jefferson Einstein Hospital, Philadelphia, Pennsylvania
| | - Radi Zaki
- Department of Surgery, Jefferson Einstein Hospital, Philadelphia, Pennsylvania.
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17
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Gao S, Gong H, Li M, Lan P, Zhang M, Kuang P, Zhang Y, Hu X, Ding C, Li Y, Ding X, Xue W, Zheng J. HLA B eplet mismatches in the context of delayed graft function and low tacrolimus trough levels are risk factors influencing the generation of de novo donor-specific antibodies and acute rejection in the early stage after kidney transplantation. Transpl Immunol 2023; 81:101955. [PMID: 37931666 DOI: 10.1016/j.trim.2023.101955] [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: 05/05/2023] [Revised: 10/30/2023] [Accepted: 11/01/2023] [Indexed: 11/08/2023]
Abstract
BACKGROUND De novo donor-specific antibody (dnDSA) generation and acute rejection (AR) are the main factors affecting long-term graft survival. This study aims to investigate human leukocyte antigen (HLA) eplet mismatching (MM), delayed graft function (DGF), and tacrolimus (TAC) trough levels on the occurrence of dnDSA and AR in the early stages after kidney transplantation (KT). METHODS This retrospective study included 526 cases of deceased donation KT. The effects of DGF, HLA eplet MM, and TAC trough levels on dnDSA and AR occurrence were analyzed with logistic regression analysis. RESULTS Multivariate logistic regression analysis showed the independent risk factor of dnDSA generation was HLA B eplet MM (OR: 1.201, 95% CI: 1.007-1.431, P = 0.041). The independent risk factors of AR occurrence include DGF (OR: 4.045, 95% CI: 1.047-15.626, P = 0.043), HLA B eplet MM (OR: 1.090, 95% CI: 1.000-1.187, P = 0.050), and TAC trough levels at 12 months (OR: 0.750, 95% CI: 565-0.997, P = 0.048). HLA B eplet MM combined with DGF and TAC trough levels at 12 months increased the predictive value of dnDSA (AUC 0.735) and AR (AUC 0.730) occurrence. HLA B eplet MM > 9 and TAC trough levels below 5.95 ng/mL at 12 months could increase the risk of early AR occurrence. CONCLUSIONS HLA B eplet MM, DGF, and TAC trough levels at 12 months after KT could affect the occurrence of dnDSA and AR in the early stage of KT.
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Affiliation(s)
- Shan Gao
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Huilin Gong
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Meihe Li
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Ping Lan
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Minyue Zhang
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Peidan Kuang
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Ying Zhang
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Xiaojun Hu
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Chenguang Ding
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Yang Li
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Xiaoming Ding
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China
| | - Wujun Xue
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
| | - Jin Zheng
- Department of Renal Transplantation, Hospital of Nephrology, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China.
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18
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Barbosa ACS, Mauroner LG, Kumar J, Sims-Lucas S. Delayed graft function post renal transplantation: a review on animal models and therapeutics. Am J Physiol Renal Physiol 2023; 325:F817-F825. [PMID: 37855040 PMCID: PMC10878700 DOI: 10.1152/ajprenal.00146.2023] [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: 05/31/2023] [Revised: 10/11/2023] [Accepted: 10/11/2023] [Indexed: 10/20/2023] Open
Abstract
The incidence of end-stage renal disease (ESRD) has been increasing worldwide. Its treatment involves renal replacement therapy, either by dialyses or renal transplantation from a living or deceased donor. Although the initial mortality rates for patients on dialysis are comparable with kidney transplant recipients, the quality of life and long-term prognosis are greatly improved in transplanted patients. However, there is a large gap between availability and need for donor kidneys. This has led to the increase in the use of expanded kidney donor criteria. Allograft dysfunction immediately after transplant sets it up for many complications, such as acute rejection and shorter allograft survival. Delayed graft function (DGF) is one of the immediate posttransplant insults to the kidney allograft, which is increasing in prevalence due to efforts to maximize the available donor pool for kidneys and use of expanded kidney donor criteria. In this review, we discuss the risk factors for DGF, its implications for long-term allograft survival, animal models of DGF, and the therapeutic options currently under evaluation for prevention and management of DGF.
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Affiliation(s)
- Anne C S Barbosa
- Division of Nephrology, Department of Pediatrics, University of Pittsburgh, UPMC Children's Hospital, Pittsburgh, Pennsylvania, United States
| | - Lillian G Mauroner
- Division of Nephrology, Department of Pediatrics, University of Pittsburgh, UPMC Children's Hospital, Pittsburgh, Pennsylvania, United States
| | - Juhi Kumar
- Division of Nephrology, Department of Pediatrics, University of Pittsburgh, UPMC Children's Hospital, Pittsburgh, Pennsylvania, United States
| | - Sunder Sims-Lucas
- Division of Nephrology, Department of Pediatrics, University of Pittsburgh, UPMC Children's Hospital, Pittsburgh, Pennsylvania, United States
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19
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Słabiak-Błaż N, Kujawa-Szewieczek A, Kolonko A, Ziółkowska J, Karkoszka H, Więcek A, Piecha G. Association between Kidney Donor Risk Index, kidney graft function and histological changes in early post-transplant graft biopsy. Clin Kidney J 2023; 16:2226-2234. [PMID: 37915886 PMCID: PMC10616491 DOI: 10.1093/ckj/sfad124] [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: 12/10/2022] [Indexed: 11/03/2023] Open
Abstract
Background Proper assessment of donor organ quality is crucial for optimal kidney allocation and best long-term outcomes. The aim of this study was to analyze the association between the Kidney Donor Risk Index (KDRI) and histological parameters in early post-transplant graft biopsy in a Polish cohort of kidney transplant recipients. Methods In 418 consecutive kidney transplant recipients, a histological evaluation of very early [at median 11 (9-13) post-transplant day] protocol core needle biopsy was performed and analyzed according to the Banff classification. Subjects were divided into quartiles of the KDRI value. Kidney graft function, patient and graft survival were also analyzed over a median follow-up period of 44 (26-56) months. Results There was a significant trend toward greater intensity of chronic histology changes along the KDRI quartiles (χ2 = 20.8; P < .001), including interstitial fibrosis, tubular atrophy, mesangial matrix increase and arteriolar hyalinosis. Stepwise multivariate regression analysis revealed that only higher KDRI value independently increased the severity of chronic graft injury (rpartial = 0.340, P < .001). KDRI values were valuable in the determination of both early and long-term graft function. Conclusion The KDRI values correlate with chronic histological changes found in early post-implantation kidney biopsies and can also be helpful in the prediction of graft outcome.
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Affiliation(s)
- Natalia Słabiak-Błaż
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland
| | - Agata Kujawa-Szewieczek
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland
| | - Aureliusz Kolonko
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland
| | - Joanna Ziółkowska
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland
| | - Henryk Karkoszka
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland
| | - Andrzej Więcek
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland
| | - Grzegorz Piecha
- Department of Nephrology, Transplantation and Internal Medicine, Medical University of Silesia, Katowice, Poland
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20
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Ma X, Moradi M, Ma X, Tang Q, Levi M, Chen Y, Zhang HK. Large Area Kidney Imaging for Pre-transplant Evaluation using Real-Time Robotic Optical Coherence Tomography. RESEARCH SQUARE 2023:rs.3.rs-3385622. [PMID: 37886456 PMCID: PMC10602184 DOI: 10.21203/rs.3.rs-3385622/v1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2023]
Abstract
Optical coherence tomography (OCT) is a high-resolution imaging modality that can be used to image microstructures of human kidneys. These images can be analyzed to evaluate the viability of the organ for transplantation. However, current OCT devices suffer from insufficient field-of-view, leading to biased examination outcomes when only small portions of the kidney can be assessed. Here we present a robotic OCT system where an OCT probe is integrated with a robotic manipulator, enabling wider area spatially-resolved imaging. With the proposed system, it becomes possible to comprehensively scan the kidney surface and provide large area parameterization of the microstructures. We verified the probe tracking accuracy with a phantom as 0.0762±0.0727 mm and demonstrated its clinical feasibility by scanning ex vivo kidneys. The parametric map exhibits fine vasculatures beneath the kidney surface. Quantitative analysis on the proximal convoluted tubule from the ex vivo human kidney yields highly clinical-relevant information.
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Affiliation(s)
- Xihan Ma
- Department of Robotics Engineering, Worcester Polytechnic Institute, MA 01609, USA
| | - Mousa Moradi
- Department of Biomedical Engineering, University of Massachusetts, Amherst, MA 01003, USA
| | - Xiaoyu Ma
- Department of Biomedical Engineering, University of Massachusetts, Amherst, MA 01003, USA
| | - Qinggong Tang
- The Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, OK 73019, USA
| | - Moshe Levi
- Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC 20057, USA
| | - Yu Chen
- Department of Biomedical Engineering, University of Massachusetts, Amherst, MA 01003, USA
| | - Haichong K Zhang
- Department of Robotics Engineering, Worcester Polytechnic Institute, MA 01609, USA
- Department of Biomedical Engineering, Worcester Polytechnic Institute, MA 01609, USA
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21
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Bi Q, Wu JY, Qiu XM, Li YQ, Yan YY, Sun ZJ, Wang W. Identification of potential necroinflammation-associated necroptosis-related biomarkers for delayed graft function and renal allograft failure: a machine learning-based exploration in the framework of predictive, preventive, and personalized medicine. EPMA J 2023; 14:307-328. [PMID: 37275548 PMCID: PMC10141843 DOI: 10.1007/s13167-023-00320-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 04/07/2023] [Indexed: 06/07/2023]
Abstract
Delayed graft function (DGF) is one of the key post-operative challenges for a subset of kidney transplantation (KTx) patients. Graft survival is significantly lower in recipients who have experienced DGF than in those who have not. Assessing the risk of chronic graft injury, predicting graft rejection, providing personalized treatment, and improving graft survival are major strategies for predictive, preventive, and personalized medicine (PPPM/3PM) to promote the development of transplant medicine. However, since PPPM aims to accurately identify disease by integrating multiple omics, current methods to predict DGF and graft survival can still be improved. Renal ischemia/reperfusion injury (IRI) is a pathological process experienced by all KTx recipients that can result in varying occurrences of DGF, chronic rejection, and allograft failure depending on its severity. During this process, a necroinflammation-mediated necroptosis-dependent secondary wave of cell death significantly contributes to post-IRI tubular cell loss. In this article, we obtained the expression matrices and corresponding clinical data from the GEO database. Subsequently, nine differentially expressed necroinflammation-associated necroptosis-related genes (NiNRGs) were identified by correlation and differential expression analysis. The subtyping of post-KTx IRI samples relied on consensus clustering; the grouping of prognostic risks and the construction of predictive models for DGF (the area under the receiver operating characteristic curve (AUC) of the internal validation set and the external validation set were 0.730 and 0.773, respectively) and expected graft survival after a biopsy (the internal validation set's 1-year AUC: 0.770; 2-year AUC: 0.702; and 3-year AUC: 0.735) were based on the least absolute shrinkage and selection operator regression algorithms. The results of the immune infiltration analysis showed a higher infiltration abundance of myeloid immune cells, especially neutrophils, macrophages, and dendritic cells, in the cluster A subtype and prognostic high-risk groups. Therefore, in the framework of PPPM, this work provides a comprehensive exploration of the early expression landscape, related pathways, immune features, and prognostic impact of NiNRGs in post-KTx patients and assesses their capabilities as.predictors of post-KTx DGF and graft loss,targets of the vicious loop between regulated tubular cell necrosis and necroinflammation for targeted secondary and tertiary prevention, andreferences for personalized immunotherapy. Supplementary Information The online version contains supplementary material available at 10.1007/s13167-023-00320-w.
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Affiliation(s)
- Qing Bi
- Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Institute of Urology, Capital Medical University, Beijing, China
| | - Ji-Yue Wu
- Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Institute of Urology, Capital Medical University, Beijing, China
| | - Xue-Meng Qiu
- Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Institute of Urology, Capital Medical University, Beijing, China
- Third Clinical Medical College, Capital Medical University, Beijing, China
| | - Yu-Qing Li
- Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Institute of Urology, Capital Medical University, Beijing, China
| | - Yu-Yao Yan
- Department of Anesthesiology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China
| | - Ze-Jia Sun
- Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Institute of Urology, Capital Medical University, Beijing, China
| | - Wei Wang
- Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
- Institute of Urology, Capital Medical University, Beijing, China
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22
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Riella J, Ferreira R, Tabbara MM, Abreu P, Ernani L, Defreitas M, Chandar J, Gaynor JJ, González J, Ciancio G. Retroperitoneal kidney transplantation with liver and native kidney mobilization: a safe technique for pediatric recipients. World J Pediatr 2023; 19:489-501. [PMID: 36474085 PMCID: PMC10149446 DOI: 10.1007/s12519-022-00658-7] [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: 09/06/2022] [Accepted: 11/16/2022] [Indexed: 12/12/2022]
Abstract
BACKGROUND Pediatric kidney transplant (KT) using larger, deceased or living donor adult kidneys can be challenging in the pediatric population due to limited space in the retroperitoneum. Liver and native kidney (L/NK) mobilization techniques can be used in smaller and younger transplant recipients to aid in retroperitoneal placement of the renal allograft. Here, we compare the clinical outcomes of pediatric retroperitoneal KT with and without L/NK mobilization. METHODS We retrospectively analyzed pediatric renal transplant recipients treated between January 2015 and May 2021. Donor and recipient demographics, intraoperative data, and recipient outcomes were included. Recipients were divided into two groups according to the surgical technique utilized: with L/NK mobilization (Group 1) and without L/NK mobilization (Group 2). Baseline variables were described using frequency distributions for categorical variables and means and standard errors for continuous variables. Tests of association with the likelihood of using L/NK mobilization were performed using standard χ2 tests, t tests, and the log-rank test. RESULTS Forty-six pediatric recipients were evaluated and categorized into Group 1 (n = 26) and Group 2 (n = 20). Recipients in Group 1 were younger (6.7 ± 0.8 years vs. 15. 3 ± 0.7, P < 0.001), shorter (109.5 ± 3.7 vs. 154.2 ± 3.8 cm, P < 0.001) and weighed less (21.4 ± 2.0 vs. 48.6 ± 3.4 kg, P < 0.001) than those in Group 2. Other baseline characteristics did not differ between Groups 1 and 2. One urologic complication was encountered in Group 2; no vascular or surgical complications were observed in either group. Additionally, no stents or drains were used in any of the patients. There were no cases of delayed graft function or graft primary nonfunction. The median follow-up of the study was 24.6 months post-transplant. Two patients developed death-censored graft failure (both in Group 2, P = 0.22), and there was one death with a functioning graft (in Group 2, P = 0.21). CONCLUSIONS Retroperitoneal liver/kidney mobilization is a feasible and safe technique that facilitates implantation of adult kidney allografts into pediatric transplant recipients with no increased risk of developing post-operative complications, graft loss, or mortality.
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Affiliation(s)
- Juliano Riella
- Department of Surgery, University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA
- Miami Transplant Institute, University of Miami Miller School of Medicine, Jackson Memorial Hospital, 1801 NW 9Th Ave, 7Th Floor, Miami, FL, 33136, USA
| | - Raphealla Ferreira
- Miami Transplant Institute, University of Miami Miller School of Medicine, Jackson Memorial Hospital, 1801 NW 9Th Ave, 7Th Floor, Miami, FL, 33136, USA
| | - Marina M Tabbara
- Department of Surgery, University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA
| | - Phillipe Abreu
- Department of Surgery, University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA
- Miami Transplant Institute, University of Miami Miller School of Medicine, Jackson Memorial Hospital, 1801 NW 9Th Ave, 7Th Floor, Miami, FL, 33136, USA
| | - Lucas Ernani
- Department of Surgery, University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA
- Miami Transplant Institute, University of Miami Miller School of Medicine, Jackson Memorial Hospital, 1801 NW 9Th Ave, 7Th Floor, Miami, FL, 33136, USA
| | - Marissa Defreitas
- Department of Pediatrics, Division of Nephrology, University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA
- Miami Transplant Institute, University of Miami Miller School of Medicine, Jackson Memorial Hospital, 1801 NW 9Th Ave, 7Th Floor, Miami, FL, 33136, USA
| | - Jayanthi Chandar
- Department of Pediatrics, Division of Nephrology, University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA
- Miami Transplant Institute, University of Miami Miller School of Medicine, Jackson Memorial Hospital, 1801 NW 9Th Ave, 7Th Floor, Miami, FL, 33136, USA
| | - Jeffrey J Gaynor
- Department of Surgery, University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA
- Miami Transplant Institute, University of Miami Miller School of Medicine, Jackson Memorial Hospital, 1801 NW 9Th Ave, 7Th Floor, Miami, FL, 33136, USA
| | - Javier González
- Servicio de Urología, Unidad de Trasplante Renal, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Gaetano Ciancio
- Department of Surgery, University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA.
- Department of Urology, University of Miami Miller School of Medicine, Jackson Memorial Hospital, Miami, FL, USA.
- Miami Transplant Institute, University of Miami Miller School of Medicine, Jackson Memorial Hospital, 1801 NW 9Th Ave, 7Th Floor, Miami, FL, 33136, USA.
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23
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Hwang CS, Kadakia Y, Sanchez-Vivaldi JA, Patel MS, Shah JA, DeGregorio L, Desai DM, Vagefi PA, MacConmara M. Delayed graft function in pediatric living donor kidney transplantation. Pediatr Transplant 2023; 27:e14432. [PMID: 36369617 DOI: 10.1111/petr.14432] [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: 07/17/2022] [Revised: 10/21/2022] [Accepted: 10/24/2022] [Indexed: 11/13/2022]
Abstract
BACKGROUND Pediatric recipients of living donor kidneys have a low rate of delayed graft function (DGF). We examined the incidence, risk factors and outcomes of DGF in pediatric patients who received a living donor allograft. METHODS The STARfile was queried to examine all pediatric patients transplanted with a living donor kidney between 2000 and 2020. Donor and recipient demographic data were examined, as were survival and outcomes. Recipients were stratified into DGF and no DGF groups. DGF was defined as the need for dialysis within the first week after transplant. RESULTS 6480 pediatric patients received a living donor (LD) kidney transplant during the study period. 269 (4.2%) developed DGF post-transplant. Donors were similar in age, creatinine, and cold ischemia time. Recipients of kidneys with DGF were similar in age, sensitization status and HLA mismatch. Focal segmental glomerulosclerosis (FSGS) was the most common diagnosis in recipients with DGF, and allograft thrombosis was the most common cause of graft loss in this group. Small recipients (weight < 15 kg) were found to have a significantly higher rate of DGF. Length of stay doubled in recipients with DGF, and rejection rates were higher post-transplant. Recipients of LD kidneys who developed DGF had significantly worse 1 year allograft survival (67% vs. 98%, p < .0001). CONCLUSIONS Pediatric living donor kidney transplant recipients who experience DGF have significantly poorer allograft survival. Optimizing the donor and recipient matching to avoid compounding risks may allow for better outcomes.
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Affiliation(s)
- Christine S Hwang
- Division of Surgical Transplantation, Department of Surgery, University Of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Pediatric Transplantation, Children's Medical Center, Dallas, TX, USA
| | - Yash Kadakia
- University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jorge A Sanchez-Vivaldi
- Division of Surgical Transplantation, Department of Surgery, University Of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Pediatric Transplantation, Children's Medical Center, Dallas, TX, USA
| | - Madhukar S Patel
- Division of Surgical Transplantation, Department of Surgery, University Of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Pediatric Transplantation, Children's Medical Center, Dallas, TX, USA
| | - Jigesh A Shah
- Division of Surgical Transplantation, Department of Surgery, University Of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Pediatric Transplantation, Children's Medical Center, Dallas, TX, USA
| | - Lucia DeGregorio
- Division of Surgical Transplantation, Department of Surgery, University Of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Pediatric Transplantation, Children's Medical Center, Dallas, TX, USA
| | - Dev M Desai
- Division of Surgical Transplantation, Department of Surgery, University Of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Pediatric Transplantation, Children's Medical Center, Dallas, TX, USA
| | - Parsia A Vagefi
- Division of Surgical Transplantation, Department of Surgery, University Of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Pediatric Transplantation, Children's Medical Center, Dallas, TX, USA
| | - Malcolm MacConmara
- Division of Surgical Transplantation, Department of Surgery, University Of Texas Southwestern Medical Center, Dallas, Texas, USA
- Division of Pediatric Transplantation, Children's Medical Center, Dallas, TX, USA
- TransMedics, Andover, MA, USA
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24
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de Rougemont O, Deng Y, Frischknecht L, Wehmeier C, Villard J, Ferrari-Lacraz S, Golshayan D, Gannagé M, Binet I, Wirthmueller U, Sidler D, Schachtner T, Schaub S, Nilsson J. Donation type and the effect of pre-transplant donor specific antibodies - Data from the Swiss Transplant Cohort Study. Front Immunol 2023; 14:1104371. [PMID: 36875145 PMCID: PMC9974644 DOI: 10.3389/fimmu.2023.1104371] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 01/30/2023] [Indexed: 02/19/2023] Open
Abstract
Introduction The type of donation may affect how susceptible a donor kidney is to injury from pre-existing alloimmunity. Many centers are, therefore, reluctant to perform donor specific antibody (DSA) positive transplantations in the setting of donation after circulatory death (DCD). There are, however, no large studies comparing the impact of pre-transplant DSA stratified on donation type in a cohort with a complete virtual cross-match and long-term follow-up of transplant outcome. Methods We investigated the effect of pre-transplant DSA on the risk of rejection, graft loss, and the rate of eGFR decline in 1282 donation after brain death (DBD) transplants and compared it to 130 (DCD) and 803 living donor (LD) transplants. Results There was a significant worse outcome associated with pre-transplant DSA in all of the studied donation types. DSA directed against Class II HLA antigens as well as a high cumulative mean fluorescent intensity (MFI) of the detected DSA showed the strongest association with worse transplant outcome. We could not detect a significant additive negative effect of DSA in DCD transplantations in our cohort. Conversely, DSA positive DCD transplants appeared to have a slightly better outcome, possibly in part due to the lower mean fluorescent intensity (MFI) of the pre-transplant DSA. Indeed when DCD transplants were compared to DBD transplants with similar MFI (<6.5k), graft survival was not significantly different. Discussion Our results suggest that the negative impact of pre-transplant DSA on graft outcome could be similar between all donation types. This suggests that immunological risk assessment could be performed in a similar way regardless of the type of donor kidney transplantation.
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Affiliation(s)
- Olivier de Rougemont
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Yun Deng
- Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland
| | - Lukas Frischknecht
- Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland
| | - Caroline Wehmeier
- Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
| | - Jean Villard
- Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland
| | - Sylvie Ferrari-Lacraz
- Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland
| | - Déla Golshayan
- Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - Monique Gannagé
- Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Isabelle Binet
- Nephrology & Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Urs Wirthmueller
- Department of Laboratory Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Daniel Sidler
- Department of Nephrology and Hypertension, Inselspital, Berne University Hospital and University of Berne, Berne, Switzerland
| | - Thomas Schachtner
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Stefan Schaub
- Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
| | - Jakob Nilsson
- Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland
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25
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Swanson KJ, Bhattarai M, Parajuli S. Delayed graft function: current status and future directions. Curr Opin Organ Transplant 2023; 28:1-7. [PMID: 36579681 DOI: 10.1097/mot.0000000000001034] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW Delayed graft function is a common early posttransplant event predictive of adverse outcomes including hospital readmission, impaired long-term graft function, and decreased graft and patient survival. The purpose of this review is to summarize recent literature describing delayed graft function in hopes of better understanding and managing this condition. RECENT FINDINGS Recent research efforts have been garnered towards risk factor modification, prevention, and earlier detection of delayed graft function. In this review, we aim to summarize current innovative approaches and future directions. SUMMARY Delayed graft function portends worse graft and patient outcomes. Continued research to prevent, and detect early perturbations in allograft function, and more optimally manage this disease will hopefully improve graft function, along with graft/patient survival.
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Affiliation(s)
- Kurtis J Swanson
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
| | - Manoj Bhattarai
- Division of Nephrology, Department of Medicine, University of Texas San Antonio, San Antonio, Texas, USA
| | - Sandesh Parajuli
- Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin
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26
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Effects of Delayed Graft Function on Transplant Outcomes: A Meta-analysis. Transplant Direct 2023; 9:e1433. [PMID: 36700066 PMCID: PMC9835896 DOI: 10.1097/txd.0000000000001433] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 10/13/2022] [Accepted: 10/18/2022] [Indexed: 01/27/2023] Open
Abstract
Delayed graft function (DGF) is a frequent complication of kidney transplantation, but its impact on long- and short-term transplant outcomes is unclear. We conducted a systematic literature search for studies published from 2007 to 2020 investigating the association between DGF and posttransplant outcomes. Forest plots stratified between center studies and registry studies were created with pooled odds ratios. Posttransplant outcomes including graft failure, acute rejection, patient mortality, and kidney function were analyzed. Of the 3422 articles reviewed, 38 papers were included in this meta-analysis. In single-center studies, patients who experienced DGF had increased graft failure (odds ratio [OR] 3.38; 95% confidence interval [CI], 1.85-6.17; P < 0.01), acute allograft rejection (OR 1.84; 95% CI, 1.30-2.61; P < 0.01), and mortality (OR 2.32; 95% CI, 1.53-3.50; P < 0.01) at 1-y posttransplant. Registry studies showed increased graft failure (OR 3.66; 95% CI, 3.04-4.40; P < 0.01) and acute rejection (OR 3.24; 95% CI, 1.88-5.59; P < 0.01) but not mortality (OR 2.27; 95% CI, 0.97-5.34; P = 0.06) at 1-y posttransplant. DGF was associated with increased odds of graft failure, acute rejection, and mortality. These results in this meta-analysis could help inform the selection process, treatment, and monitoring of transplanted kidneys at high risk of DGF.
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27
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Reid TD, Kratzke I, Dayal D, Raff L, Serrano P, Kumar A, Boddie O, Zendel A, Gallaher J, Carlson R, Boone J, Charles AG, Desai CS. The role of extracorporeal membrane oxygenation in adult kidney transplant patients: A qualitative systematic review of literature. Artif Organs 2023; 47:24-37. [PMID: 35986612 DOI: 10.1111/aor.14376] [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: 04/20/2022] [Revised: 06/23/2022] [Accepted: 07/26/2022] [Indexed: 01/04/2023]
Abstract
BACKGROUND A paucity of evidence exists regarding the risks and benefits of Extracorporeal Membrane Oxygenation (ECMO) in adult kidney transplantation. METHODS This was a systematic review conducted from Jan 1, 2000 to April 24, 2020 of adult kidney transplant recipients (pre- or post- transplant) and donors who underwent veno-arterial or veno-venous ECMO cannulation. Death and graft function were the primary outcomes, with complications as secondary outcomes. RESULTS Twenty-three articles were identified that fit inclusion criteria. 461 donors were placed on ECMO, with an overall recipient 12-month mortality rate of 1.3% and a complication rate of 61.5%, the majority of which was delayed graft function. Fourteen recipients were placed on ECMO intraoperatively or postoperatively, with infection as the most common indication for ECMO. The 90-day mortality rate for recipients on ECMO was 42.9%, with multisystem organ failure and infection as the ubiquitous causes of death. 35.7% of patients experienced rejection within 6 months of decannulation, yet all were successfully treated. CONCLUSIONS ECMO use in adult kidney transplantation is a useful adjunct. Recipient morbidity and mortality from donors placed on ECMO mirrors that of recipients from standard criteria donors. The morbidity and mortality of recipients placed on ECMO are also similar to other patient populations requiring ECMO.
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Affiliation(s)
- Trista D Reid
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Trauma and Acute Care Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Ian Kratzke
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Diana Dayal
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Lauren Raff
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Trauma and Acute Care Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Pablo Serrano
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Transplant Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Aman Kumar
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Transplant Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Olivia Boddie
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Trauma and Acute Care Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Alex Zendel
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Transplant Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Jared Gallaher
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Trauma and Acute Care Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Rebecca Carlson
- Health Sciences Library, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Joshua Boone
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Anthony G Charles
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Trauma and Acute Care Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Chirag S Desai
- Department of Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.,Division of Transplant Surgery, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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Song J, Yao Y, He Y, Lin S, Pan S, Zhong M. Contrast-Enhanced Ultrasonography Value for Early Prediction of Delayed Graft Function in Renal Transplantation Patients. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2023; 42:201-210. [PMID: 35603734 DOI: 10.1002/jum.16010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 04/11/2022] [Accepted: 05/03/2022] [Indexed: 06/15/2023]
Abstract
OBJECTIVES Delayed graft function (DGF) is a common early complication after kidney transplantation. The aim of the present study was to evaluate the value of contrast-enhanced ultrasonography (CEUS) in the early prediction of DGF after kidney transplantation. METHODS A total of 89 renal transplant recipients were retrospectively enrolled and divided into DGF group or normal graft function (NGF) group according to the allograft function. Conventional Doppler ultrasound and CEUS examination data on the first postoperative day were collected and analyzed. RESULTS The resistive indices of segmental and interlobar artery in the DGF group were significantly higher than those in the NGF group (0.71 ± 0.17 versus 0.63 ± 0.08, P = .006; 0.70 ± 0.16 versus 0.62 ± 0.08, P = .004, respectively). The patients experiencing DGF had significantly lower PI-c (14.7 dB ± 6.1 dB versus 18.5 dB ± 3.3 dB, P = .001) and smaller AUC-c (779.8 ± 375.8 dB·seconds versus 991.0 ± 211.7 dB·seconds, P = .003), as well as significantly lower PI-m (12.6 dB ± 5.9 dB versus 15.9 dB ± 3.9 dB, P = .006), shorter MTT-m (30.7 ± 9.4 seconds versus 36.3 ± 7.1 seconds, P = .01), and smaller AUC-m (P = .007). Multivariate analysis demonstrated that PI-c, AUC-c, and MTT-m were independent risk factors for DGF. The area under the receiver operating characteristic curve values of the combined predicted value (PI-c + MTT-m, PI-c + AUC-c + MTT-m) of DGF incidence were bigger than that of PI-c, AUC-c, or MTT-m. CONCLUSIONS CEUS parameters of the cortex and medulla have a good value for an early prediction of DGF after renal transplantation.
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Affiliation(s)
- Jieqiong Song
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yao Yao
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yizhou He
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shilong Lin
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Simeng Pan
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ming Zhong
- Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
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Belhoste M, Allenbach G, Agius T, Meier RPH, Venetz JP, Corpataux JM, Schneider A, Golshayan D, Prior JO, Déglise S, Nicod-Lalonde M, Longchamp A. Role of post-transplant graft scintigraphy in kidney donation after circulatory death. FRONTIERS IN TRANSPLANTATION 2022; 1:1065415. [PMID: 38994379 PMCID: PMC11235226 DOI: 10.3389/frtra.2022.1065415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/09/2022] [Accepted: 11/29/2022] [Indexed: 07/13/2024]
Abstract
Background There is no consensus on how to predict post-transplant function of donation after circulatory death (DCD) kidneys. Thus, we aimed to identify renal scintigraphy parameters that could predict 1-year kidney function. Methods In this single center study, we included all consecutive DCD kidney recipients between 2013 and 2021 (n = 29). Patients who did not have a scintigraphy within 10 days of transplantation (n = 3), recipients of multiple organs and less than 18 years old were excluded (n = 1). Primary endpoint was the estimated glomerular filtration rate (eGFR). Results Median eGFR and serum creatinine at 1 year were 67 µmol/L (56-81) and 111 ml/min (99-132), respectively. Among parameters tested, the 3rd/2nd-minute activity ratio had the best diagnostic performance (AUC: 0.74 and 0.71, for eGFR and creatinine) 1 year post transplantation. Using 1.21 as the best cut off, the 3rd/2nd-minute activity ratio specificity and sensitivity to predict eGFR >60 ml/min was 0.82 and 0.83. Renal function was significantly better at 1 week, 3, 6, and 12 months after transplantation in patients with 3rd/2nd-minute activity ratios above 1.21. Conclusion This study suggests that the 3rd/2nd-minute activity ratio can predict graft function at 1 year. The benefit of post-transplant scintigraphy should be further validated in a prospective cohort.
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Affiliation(s)
- Manon Belhoste
- Department of Vascular Surgery, Lausanne University Hospital, Lausanne, Switzerland
| | - Gilles Allenbach
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Thomas Agius
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland
| | - Raphael P. H. Meier
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, United States
| | - Jean-Pierre Venetz
- Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - Jean-Marc Corpataux
- Department of Vascular Surgery, Lausanne University Hospital, Lausanne, Switzerland
| | - Antoine Schneider
- Adult Intensive Care Unit, Lausanne University Hospital, Lausanne, Switzerland
| | - Déla Golshayan
- Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - John O. Prior
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Sébastien Déglise
- Department of Vascular Surgery, Lausanne University Hospital, Lausanne, Switzerland
| | - Marie Nicod-Lalonde
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital, Lausanne, Switzerland
| | - Alban Longchamp
- Department of Vascular Surgery, Lausanne University Hospital, Lausanne, Switzerland
- Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland
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Zhang F, Liang J, Xiong Y, Zhang F, Wu K, Wang W, Yuan J, Lin T, Wang X. Serum uric acid as a risk factor for rejection after deceased donor kidney transplantation: A mono-institutional analysis of paired kidneys. Front Immunol 2022; 13:973425. [PMID: 36578496 PMCID: PMC9791182 DOI: 10.3389/fimmu.2022.973425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Accepted: 11/23/2022] [Indexed: 12/14/2022] Open
Abstract
Background Deceased donor kidney transplantation (DDKT) is a major therapeutic option for patients with end-stage renal diseases. Although medical techniques improved in recent years, acute or chronic rejection after DDKT is not uncommon and often results in poor graft survival. Therefore, the determination of risk factors is very important to stratify patients and to improve outcomes. This study aims to evaluate the risk factors for treated rejection (TR) of patients after DDKT. Methods Clinical data of deceased donors and corresponding recipients were retrospectively collected. The primary outcome was TR defined as the treatment for rejection within 24 months after DDKT. Univariate comparisons of baseline characteristics were performed with Chi-square test, t-test, and Mann-Whitney U test. Logistic regression was constructed to analyze potential risk factors. Receiver operating characteristic (ROC) curve and Jordan index were generated to determine the optimal cutoff value. The association between continuous variables and TR was examined and visualized by using restricted cubic spline (RCS) models. Results Data of 123 deceased donors and 246 recipients were obtained and analyzed. The median age was 41 (4-62) years for recipients and 39 (1-65) years for donors. The recipients who died or suffered graft loss during the follow-up period were 8 (3.3%) and 12 (4.9%), respectively. After univariate analysis and subsequent multivariate analysis, the preoperative serum uric acid (OR, 2.242; 95% CI, 1.037-4.844; P = 0.040), platelet (OR, 2.163; 95% CI, 1.073-4.361, P = 0.031), absolute neutrophil count (OR, 2.183; 95% CI, 1.025-4.649; P = 0.043), and HLA-DQ mismatch (OR, 2.102; 95% CI, 1.093-4.043; P = 0.026) showed statistical significance. RCS models showed that patients with higher levels of uric acid had increased risk of TR. Conclusions Serum uric acid and other three indicators were found to be the independent risk factors for TR, which may contribute to stratify patients and develop personalized regimen in perioperative period.
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Xiao Q, Zhang X, Zhao S, Yan Y, Wan H, Xiao J. A Multiparametric Nomogram for Predicting Delayed Graft Function in Adult Recipients of Pediatric Donor Kidneys. Transplant Proc 2022; 54:2147-2153. [DOI: 10.1016/j.transproceed.2022.08.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 08/09/2022] [Accepted: 08/26/2022] [Indexed: 11/13/2022]
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Zawistowski M, Nowaczyk J, Domagała P. Peritoneal dialysis catheter removal at the time or after kidney transplantation: a systematic review and meta-analysis. Langenbecks Arch Surg 2022; 407:2651-2662. [PMID: 35945300 PMCID: PMC9640428 DOI: 10.1007/s00423-022-02637-y] [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: 01/30/2022] [Accepted: 07/31/2022] [Indexed: 11/24/2022]
Abstract
PURPOSE An increasing number of patients treated with peritoneal dialysis eventually undergo kidney transplantation. Owing to opposing reports, we aimed to find evidence about the best time for peritoneal dialysis catheter removal in transplant patients. METHODS We conducted a systematic review and random effects meta-analysis of non-randomized studies of intervention comparing patients with peritoneal dialysis catheters left in place or removed during kidney transplantation in regard to the need for dialysis and occurrence of catheter-related complications. We searched (last update on 8 December 2021) PubMed, Embase, Scopus, and Web of Science for eligible studies. ROBINS-I tool and funnel plot asymmetry analysis were used to assess the quality of included articles. RESULTS Eight observational studies were evaluated. Five of them, which involved 338 patients, were included in a meta-analysis. All were at moderate to serious risk of bias. The odds of needing dialysis are more than twice as high for patients with peritoneal dialysis catheters left in situ (pooled odds ratio, 2.21; 95% confidence interval [CI], 1.03 to 4.73; I2 = 0%). No statistically significant difference was noted when adult and pediatric subgroups were compared (Q = 0.13, P = .720). More individuals with catheters left in place required dialysis (pooled prevalence, 20.9%; 95% CI, 13.6 to 30.7%; I2 = 59% vs. 12.4%; 95% CI, 5.6 to 25.2%; I2 = 0%) and experienced catheter-related infections. CONCLUSION Available evidence is scarce. Unless new data from a randomized controlled trial are available, the dilemma of peritoneal dialysis catheter removal cannot be solved. TRIAL REGISTRATION PROSPERO Protocol ID: CRD42020207707.
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Affiliation(s)
- Michał Zawistowski
- Department of General and Transplantation Surgery, Medical University of Warsaw, Nowogrodzka 59, 02-006, Warsaw, Poland
- Military Institute of Medicine, Warsaw, Poland
| | - Joanna Nowaczyk
- Department of General and Transplantation Surgery, Medical University of Warsaw, Nowogrodzka 59, 02-006, Warsaw, Poland
| | - Piotr Domagała
- Department of General and Transplantation Surgery, Medical University of Warsaw, Nowogrodzka 59, 02-006, Warsaw, Poland.
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Lung Transplantation Advanced Prediction Tool: Determining Recipient's Outcome for a Certain Donor. Transplantation 2022; 106:2019-2030. [PMID: 35389371 PMCID: PMC9521589 DOI: 10.1097/tp.0000000000004131] [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: 02/04/2023]
Abstract
BACKGROUND Many risk-prediction models for lung transplantation are centered on recipient characteristics and do not account for impact of donor and transplant-related factors or only examine short-term outcomes (eg, predicted 1-y survival). We sought to develop a comprehensive model guiding recipient-donor matching. METHODS We identified double lung transplant recipients (≥12 y old) in the United Network for Organ Sharing Registry (2005-2020) to develop a risk scoring tool. Cohort was divided into derivation and validation sets. A total of 42 recipient, donor, and transplant factors were included in the analysis. Lasso method was used for variable selection. Survival was estimated using Cox-proportional hazard models. An interactive web-based tool was developed for clinical use. RESULTS A derivation cohort (n = 10 660) informed the model with 13-recipient, 4-donor, and 2-transplant variables. Adjusted risk scores were computed for every transplant and grouped into 3 clusters. Model-estimated survival probabilities were similar to the observed in the validation cohort (n = 4464) for all clusters. The mortality increases for medium- and high-risk groups was similar in both derivation and validation cohorts (C statistics for 1-, 5-, and 10-y survival were 0.67, 0.64, and 0.72, respectively). The web-based application estimated 1-, 5-, 10-y survival and half-life for low- (92%, 73%, 52%; 10.5 y), medium- (89%, 62%, 38%; 7.3 y), and high-risk clusters (85%, 52%, 26%; 5.2 y). CONCLUSIONS Advanced methods incorporating machine/deep learning led to a risk scoring model (including recipient, donor, and transplant factors) and a web-based clinical tool providing short- and long-term survival probabilities for recipient-donor matches. This will enable risk-based matching that could improve utilization of and benefit from a limited donor pool.
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Abstract
BACKGROUND Quality in kidney transplantation is measured using 1-year patient and graft survival. Because 1-year patient and graft survival exceed 95%, this metric fails to measure a spectrum of quality. Textbook outcomes (TO) are a composite quality metric offering greater depth and resolution. We studied TO after living donor (LD) and deceased donor (DD) kidney transplantation. STUDY DESIGN United Network for Organ Sharing data for 69,165 transplant recipients between 2013 and 2017 were analyzed. TO was defined as patient and graft survival of 1 year or greater, 1-year glomerular filtration rate of greater than 40 mL/min, absence of delayed graft function, length of stay of 5 days or less, no readmissions during the first 6 months, and no episodes of rejection during the first year after transplantation. Bivariate analysis identified characteristics associated with TO, and covariates were incorporated into multivariable models. Five-year conditional survival was measured, and center TO rates were corrected for case complexity to allow center-level comparisons. RESULTS The national average TO rates were 54.1% and 31.7% for LD and DD transplant recipients. The hazard ratio for death at 5 years for recipients who did not experience TO was 1.92 (95% CI 1.68 to 2.18, p ≤ 0.0001) for LD transplant recipients and 2.08 (95% CI 1.93 to 2.24, p ≤ 0.0001) for DD transplant recipients. Center-level comparisons identify 18% and 24% of centers under-performing in LD and DD transplantation. High rates of TO do not correlate with transplantation center volume. CONCLUSION Kidney transplant recipients who experience TO have superior long-term survival. Textbook outcomes add value to the current standards of 1-year patient and graft survival.
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Okumura K, Misawa R, Ohira S, Dhand A, Kai M, Sogawa H, Veillette G, John D, Diflo T, Nishida S. Does utilization of heart machine perfusion for donation after cardiac death transplantation affect outcomes of other abdominal transplanted organs? Clin Transplant 2022; 36:e14751. [PMID: 35706100 DOI: 10.1111/ctr.14751] [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: 05/01/2022] [Revised: 05/15/2022] [Accepted: 06/03/2022] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Machine perfusion of heart for donation after circulatory death (DCD) is being increasingly utilized. Current protocols for utilizing heart DCD's machine perfusion might prolong donor warm ischemic time for nonheart organs. The aim of this study was to analyze the effects of utilizing heart machine perfusion on liver and kidney transplants from the same donor. METHODS We analyzed data of DCD donors from the United Network for Organ Sharing (UNOS) from January-2020 to September-2021 among two groups: donors with heart machine perfusion (HM) and without heart machine perfusion (NHM). Propensity score (PS) matching was performed to compare the short-term outcomes of liver and kidney transplants between two groups. RESULTS Total of 102 liver and 319 kidney transplants were performed using organs from donors with HM. After PS matching, no statistically significant difference was seen in 1-year graft survival (GS) for both liver and kidney transplants between two groups (liver HM 90.6% vs. NHM 90.2%, p = .47; kidney HM 95.2% vs. NHM 92.9%, p = .40). There was no difference in the delayed graft function (DGF) rates in kidney transplantation (KT) (HM 42% vs. NHM 35%, p = .062). CONCLUSION Utilization of heart machine perfusion in DCD donors had no significant impact on 1-year outcomes of liver and kidney transplantation.
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Affiliation(s)
- Kenji Okumura
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA
| | - Ryosuke Misawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA
| | - Suguru Ohira
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA.,Department of Surgery, Division of Cardiothoracic Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Abhay Dhand
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA.,Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, New York, USA
| | - Masashi Kai
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA.,Department of Surgery, Division of Cardiothoracic Surgery, Westchester Medical Center, Valhalla, New York, USA
| | - Hiroshi Sogawa
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA
| | - Gregory Veillette
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA
| | - Devon John
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA
| | - Thomas Diflo
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA
| | - Seigo Nishida
- Department of Surgery, Westchester Medical Center and New York Medical College, Valhalla, New York, USA
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Jan MY, Moe SM, Adebiyi O, Chen J, Powelson J, Burney HN, Yaqub MS, Mishler DP, Moorthi RN, Taber TE, Anderson MD, Li Y, Li X, Fridell JA, Goggins WC, Sharfuddin AA. Vasopressin for Post-kidney Transplant Hypotension. Kidney Int Rep 2022; 7:1364-1376. [PMID: 35694563 PMCID: PMC9174042 DOI: 10.1016/j.ekir.2022.03.035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 03/24/2022] [Accepted: 03/29/2022] [Indexed: 12/02/2022] Open
Abstract
Introduction Hypotension after deceased donor kidney transplant (DDKT) is a risk factor for delayed graft function (DGF) and poor graft survival (GS). We hypothesize that vasopressin use in hypotensive DDKT recipients (DDKTRs) to increase blood pressure (BP) reduces DGF rates and is safe without increasing mortality. Methods Group with vasopressin "study group" (n = 45) was defined as DDKTRs between 2012 and 2017 who required vasopressin for hypotension systolic BP (SBP) <120 mm Hg or diastolic BP (DBP) <60 mm Hg. DDKTRs with no-vasopressin "comparison group" (n = 90) were propensity score-matched DDKTRs between 2012 and 2017 without vasopressin use. Primary outcomes were GS, creatinine and allograft biopsy rate at 1 year, DGF rate, and death during transplant hospitalization. Results Vasopressin group had lower mean maximum and minimum SBP and DBP in the operating room (OR). Median vasopressin start time post-DDKT was 2 hours (interquartile range [IQR] 1-6), and duration of use was 42 hours (IQR 24-63). DGF, creatinine at 1 year, and allograft biopsy rates were comparable. No deaths occurred during transplant hospitalization. Multivariable analysis did not find an effect of vasopressin use on GS. Conclusion Treatment of hypotensive DDKTRs with vasopressin is safe and facilitated similar graft function and survival with that of nonhypotensive patients. In the absence of a randomized control trial, our study supports the safety of vasopressin therapy to prevent the adverse effects of hypotension.
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Affiliation(s)
- Muhammad Y. Jan
- Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Sharon M. Moe
- Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Indiana Clinical and Translational Sciences Institute, Indianapolis, Indiana, USA
| | - Oluwafisayo Adebiyi
- Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Jeannie Chen
- Department of Pharmacy, Indiana University Health, Indianapolis, Indiana, USA
| | - John Powelson
- Division Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Heather N. Burney
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Muhammad S. Yaqub
- Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Dennis P. Mishler
- Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Ranjani N. Moorthi
- Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Tim E. Taber
- Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Melissa D. Anderson
- Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Yang Li
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Xiaochun Li
- Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Jonathan A. Fridell
- Division Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - William C. Goggins
- Division Transplant Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Asif A. Sharfuddin
- Division of Nephrology and Hypertension, Indiana University School of Medicine, Indianapolis, Indiana, USA
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Stirnadel-Farrant HA, Mu G, Cooper-Blenkinsopp S, Schroyer RO, Thorneloe KS, Harrison EM, Andrews SMS. Predictive Value of Delayed Graft Function Definitions Following Donation After Circulatory Death Renal Transplantation in the United Kingdom. TRANSPLANT RESEARCH AND RISK MANAGEMENT 2022. [DOI: 10.2147/trrm.s320221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Kang SW, Kang SW, Ban JY, Park MS. Identification of Multiple Hub Genes in Acute Kidney Injury after Kidney Transplantation by Bioinformatics Analysis. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:681. [PMID: 35630098 PMCID: PMC9145685 DOI: 10.3390/medicina58050681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 05/15/2022] [Accepted: 05/17/2022] [Indexed: 11/21/2022]
Abstract
Background and Objectives: The molecular mechanisms of the development of acute kidney injury (AKI) after kidney transplantation are not yet clear. The aim of this study was to confirm the genes and mechanisms related to AKI after transplantation. Materials and Methods: To investigate potential genetic targets for AKI, an analysis of the gene expression omnibus database was used to identify key genes and pathways. After identification of differentially expressed genes, Kyoto Encyclopedia of Genes and Genome pathway enrichment analyses were performed. We identified the hub genes and established the protein-protein interaction network. Results: Finally, we identified 137 differentially expressed genes (59 upregulated genes and 16 downregulated genes). AKAP12, AMOT, C3AR1, LY96, PIK3AP1, PLCD4, PLCG2, TENM2, TLR2, and TSPAN5 were filtrated by the hub genes related to the development of post-transplant AKI from the Protein-Protein Interaction (PPI) network. Conclusions: This may provide important evidence of the diagnostic and therapeutic biomarker of AKI.
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Affiliation(s)
- Sang-Wook Kang
- Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, Seoul 02447, Korea;
| | - Sung-Wook Kang
- Neuroscience Center of Excellence, Louisiana State University School of Medicine, New Orleans, LA 70112, USA;
| | - Ju-Yeon Ban
- Department of Dental Pharmacology, School of Dentistry, Dankook University, Cheonan 31116, Korea
| | - Min-Su Park
- Department of Surgery, School of Medicine, Kyung Hee University, Seoul 02447, Korea
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Bachmann Q, Haberfellner F, Büttner-Herold M, Torrez C, Haller B, Assfalg V, Renders L, Amann K, Heemann U, Schmaderer C, Kemmner S. The Kidney Donor Profile Index (KDPI) Correlates With Histopathologic Findings in Post-reperfusion Baseline Biopsies and Predicts Kidney Transplant Outcome. Front Med (Lausanne) 2022; 9:875206. [PMID: 35573025 PMCID: PMC9100560 DOI: 10.3389/fmed.2022.875206] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2022] [Accepted: 03/28/2022] [Indexed: 11/29/2022] Open
Abstract
Background The increasing organ shortage in kidney transplantation leads to the necessity to use kidneys previously considered unsuitable for transplantation. Numerous studies illustrate the need for a better decision guidance rather than only the classification into kidneys from standard or expanded criteria donors referred to as SCD/ECD-classification. The kidney donor profile index (KDPI) exhibits a score utilizing a much higher number of donor characteristics. Moreover, graft biopsies provide an opportunity to assess organ quality. Methods In a single center analysis 383 kidney transplantations (277 after deceased and 106 after living donation) performed between January 1st, 2006, and December 31st, 2016, retrospectively underwent SCD/ECD and KDPI scoring. Thereby, the quality of deceased donor kidneys was assessed by using the KDPI and the living donor kidneys by using the living KDPI, in the further analysis merged as (L)KDPI. Baseline biopsies taken 10 min after the onset of reperfusion were reviewed for chronic and acute lesions. Survival analyses were performed using Kaplan-Meier analysis and Cox proportional hazards analysis within a 5-year follow-up. Results The (L)KDPI correlated with glomerulosclerosis (r = 0.30, p < 0.001), arteriosclerosis (r = 0.33, p < 0.001), interstitial fibrosis, and tubular atrophy (r = 0.28, p < 0.001) as well as the extent of acute tubular injury (r = 0.20, p < 0.001). The C-statistic of the (L)KDPI concerning 5-year death censored graft survival was 0.692. Around 48% of ECD-kidneys were classified as (L)KDPI<85%. In a multivariate Cox proportional hazard analysis including (preformed) panel reactive antibodies, cold ischemia time, (L)KDPI, and SCD/ECD-classification, the (L)KDPI was significantly associated with risk of graft loss (hazard ratio per 10% increase in (L)KDPI: 1.185, 95% confidence interval: 1.033–1.360, p = 0.025). Survival analysis revealed decreased death censored (p < 0.001) and non-death censored (p < 0.001) graft survival in kidneys with an increasing (L)KDPI divided into groups of <35, 35–85, and >85%, respectively. Conclusion With a higher granularity compared to the SCD/ECD-classification the (L)KDPI is a promising tool to judge graft quality. The correlation with chronic and acute histological lesions in post-reperfusion kidney biopsies underlines the descriptive value of the (L)KDPI. However, its prognostic value is limited and underlines the urgent need for a more precise prognostic tool adopted to European kidney transplant conditions.
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Affiliation(s)
- Quirin Bachmann
- Department of Nephrology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Flora Haberfellner
- Department of Nephrology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Maike Büttner-Herold
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany
| | - Carlos Torrez
- Department of Nephrology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Bernhard Haller
- School of Medicine, Institute of AI and Informatics in Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Volker Assfalg
- Department of Surgery, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Lutz Renders
- Department of Nephrology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Kerstin Amann
- Department of Nephropathology, Institute of Pathology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany
| | - Uwe Heemann
- Department of Nephrology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Christoph Schmaderer
- Department of Nephrology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
| | - Stephan Kemmner
- Department of Nephrology, School of Medicine, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
- *Correspondence: Stephan Kemmner
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Budhiraja P, Reddy KS, Butterfield RJ, Jadlowiec CC, Moss AA, Khamash HA, Kodali L, Misra SS, Heilman RL. Duration of delayed graft function and its impact on graft outcomes in deceased donor kidney transplantation. BMC Nephrol 2022; 23:154. [PMID: 35440023 PMCID: PMC9017045 DOI: 10.1186/s12882-022-02777-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Accepted: 03/30/2022] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND There is controversy regarding the impact of delayed graft function (DGF) on kidney transplant outcomes. We hypothesize that the duration of DGF, rather than DGF itself, is associated with long-term kidney graft function. METHODS We analyzed all deceased donor kidney transplants (DDKT) done at our center between 2008 to 2020. We determined factors associated with DGF duration. DGF duration was assessed at three 14-day intervals: < 14 DGF days, 14-27 DGF days, > 28 DGF days. We studied the impact of DGF duration on survival and graft function and resource utilization, including hospital length of stay and readmissions. RESULTS 1714 DDKT recipients were included, 59.4% (n = 1018) had DGF. The median DGF duration was 10 days IQR (6,15). The majority of recipients (95%) had resolution of DGF within 28 days. Donor factors associated with DGF days were longer cold ischemia time, donor on inotropes, older age, donation after circulatory death, higher terminal creatinine, and hypertension. Recipient factors associated with increased DGF duration included male sex, length on dialysis before transplant, and higher body mass index. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. The median length of stay was 3 days. However, readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted > 28 days. CONCLUSIONS Inferior graft survival was observed only in recipients of DDKT with DGF lasting beyond 28 days. DGF lasting < 28 days had no impact on graft survival. Duration of DGF, rather than DGF itself, is associated with graft survival. TRIAL REGISTRATION Retrospective study approved by Mayo Clinic IRB number ID: 20-011561.
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Affiliation(s)
- Pooja Budhiraja
- Division of Nephrology, Mayo Clinic Hospital, 5777 East Mayo Blvd, Phoenix, AZ, 85054, USA.
| | - Kunam S Reddy
- Department of Surgery, Mayo Clinic, 5777 East Mayo Blvd, Phoenix, AZ, 85054, USA
| | | | - Caroline C Jadlowiec
- Department of Surgery, Mayo Clinic, 5777 East Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Adyr A Moss
- Department of Surgery, Mayo Clinic, 5777 East Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Hassan A Khamash
- Division of Nephrology, Mayo Clinic Hospital, 5777 East Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Lavanya Kodali
- Division of Nephrology, Mayo Clinic Hospital, 5777 East Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Suman S Misra
- Division of Nephrology, Mayo Clinic Hospital, 5777 East Mayo Blvd, Phoenix, AZ, 85054, USA
| | - Raymond L Heilman
- Division of Nephrology, Mayo Clinic Hospital, 5777 East Mayo Blvd, Phoenix, AZ, 85054, USA
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41
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Castro Filho JBSD, Pompeo JDC, Machado RB, Gonçalves LFS, Bauer AC, Manfro RC. Delayed Graft Function Under the Microscope: Surveillance Biopsies in Kidney Transplantation. Transpl Int 2022; 35:10344. [PMID: 35401043 PMCID: PMC8988887 DOI: 10.3389/ti.2022.10344] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Accepted: 02/24/2022] [Indexed: 11/13/2022]
Abstract
Delayed graft function (DGF) is a common complication of kidney transplantation and frequently leads to the necessity of surveillance biopsies. The purpose of this study is to describe the histological findings in surveillance biopsies of deceased donor kidney transplant recipients and evaluate the risk factors for graft outcomes. This is a monocentric, retrospective study including kidney transplant recipients that underwent a graft biopsy during the DGF period between January 2006 and July 2019. 356 biopsies were performed in 335 deceased donor transplant recipients. Biopsies were analyzed according to the Banff classification. The main histological findings were: acute tubular necrosis in 150 biopsies (42.1%), acute rejection in 96 biopsies (26.9%), and borderline findings in 91 biopsies (25.5%). In the multivariate analysis, recipient age (p = 0.028) and DGF duration (p = 0.005) were associated with rejection, antibody-induction with anti-thymocyte globulin (ATG) was protective (p = 0.001). The occurrence of rejection was associated with lower death-censored graft survival (log-rank; p = 0.009). Surveillance biopsies of kidney grafts experiencing DGF remain an essential tool for the care of kidney transplant recipients. The recipient’s age and duration of DGF are independent risk factors for acute rejection, while antibody-induction therapy with ATG is associated with protection from its occurrence.
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Affiliation(s)
| | | | - Rafael Berlezi Machado
- UFRGS Medical School, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Luiz Felipe Santos Gonçalves
- Division of Nephrology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.,UFRGS Medical School, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Andrea Carla Bauer
- Division of Nephrology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.,UFRGS Medical School, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil
| | - Roberto Ceratti Manfro
- Division of Nephrology, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.,UFRGS Medical School, Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.,Division of Transplantation, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil
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Ascorbic acid in solid organ transplantation: a literature review. Clin Nutr 2022; 41:1244-1255. [DOI: 10.1016/j.clnu.2022.04.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 04/04/2022] [Accepted: 04/06/2022] [Indexed: 11/19/2022]
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Singh N, Logan A, Schenk A, Bumgardner G, Brock G, El-Hinnawi A, Rajab A, Washburn K. Machine perfusion of kidney allografts affects early but not late graft function. Am J Surg 2022; 223:804-811. [PMID: 34253338 PMCID: PMC9017432 DOI: 10.1016/j.amjsurg.2021.06.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 06/02/2021] [Accepted: 06/30/2021] [Indexed: 11/01/2022]
Abstract
BACKGROUND Hypothermic machine perfusion (HMP) parameters are influenced by donor variables which further affect recipient outcome. Interplay between these parameters can help to predict kidney performance on pump and the long term outcome. METHODS All the kidneys transplanted at our center between May 2013 through November 2017 were included in the study. Donor and recipient data was obtained from internal database. Multiple logistic regression models with backward selection were used to determine significant donor and pump variables. RESULTS Donor BMI, KDPI, age and donor sex had a significant association with pump flow. Donor sex, donor type, KDPI and age had significant effect on RI. Diastolic pressure and KDPI were significantly associated with DGF. Duration on pump, KDPI, flow, donor creatinine and type of donor were significantly associated with day 5 creatinine. KDPI was significantly associated with Day 365 creatinine. CONCLUSION HMP effects early graft function while the long term function depends on donor parameters.
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Affiliation(s)
- Navdeep Singh
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
| | - April Logan
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Austin Schenk
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Ginny Bumgardner
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Guy Brock
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Ashraf El-Hinnawi
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Amer Rajab
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Kenneth Washburn
- Division of Transplantation, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
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Becker F, Kebschull L, Rieger C, Mohr A, Heitplatz B, Van Marck V, Hansen U, Ansari J, Reuter S, Strücker B, Pascher A, Brockmann JG, Castor T, Alexander JS, Gavins FNE. Bryostatin-1 Attenuates Ischemia-Elicited Neutrophil Transmigration and Ameliorates Graft Injury after Kidney Transplantation. Cells 2022; 11:cells11060948. [PMID: 35326400 PMCID: PMC8946580 DOI: 10.3390/cells11060948] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 03/04/2022] [Accepted: 03/09/2022] [Indexed: 12/19/2022] Open
Abstract
Ischemia reperfusion injury (IRI) is a form of sterile inflammation whose severity determines short- and long-term graft fates in kidney transplantation. Neutrophils are now recognized as a key cell type mediating early graft injury, which activates further innate immune responses and intensifies acquired immunity and alloimmunity. Since the macrolide Bryostatin-1 has been shown to block neutrophil transmigration, we aimed to determine whether these findings could be translated to the field of kidney transplantation. To study the effects of Bryostatin-1 on ischemia-elicited neutrophil transmigration, an in vitro model of hypoxia and normoxia was equipped with human endothelial cells and neutrophils. To translate these findings, a porcine renal autotransplantation model with eight hours of reperfusion was used to study neutrophil infiltration in vivo. Graft-specific treatment using Bryostatin-1 (100 nM) was applied during static cold storage. Bryostatin-1 dose-dependently blocked neutrophil activation and transmigration over ischemically challenged endothelial cell monolayers. When applied to porcine renal autografts, Bryostatin-1 reduced neutrophil graft infiltration, attenuated histological and ultrastructural damage, and improved renal function. Our novel findings demonstrate that Bryostatin-1 is a promising pharmacological candidate for graft-specific treatment in kidney transplantation, as it provides protection by blocking neutrophil infiltration and attenuating functional graft injury.
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Affiliation(s)
- Felix Becker
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, 48149 Münster, Germany; (F.B.); (L.K.); (C.R.); (A.M.); (B.S.); (A.P.); (J.G.B.)
| | - Linus Kebschull
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, 48149 Münster, Germany; (F.B.); (L.K.); (C.R.); (A.M.); (B.S.); (A.P.); (J.G.B.)
| | - Constantin Rieger
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, 48149 Münster, Germany; (F.B.); (L.K.); (C.R.); (A.M.); (B.S.); (A.P.); (J.G.B.)
| | - Annika Mohr
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, 48149 Münster, Germany; (F.B.); (L.K.); (C.R.); (A.M.); (B.S.); (A.P.); (J.G.B.)
| | - Barbara Heitplatz
- Gerhard Domagk Institute of Pathology, University Hospital Münster, 48149 Münster, Germany; (B.H.); (V.V.M.)
| | - Veerle Van Marck
- Gerhard Domagk Institute of Pathology, University Hospital Münster, 48149 Münster, Germany; (B.H.); (V.V.M.)
| | - Uwe Hansen
- Department of Molecular Medicine, Institute for Musculoskeletal Medicine, University Hospital Münster, 48149 Münster, Germany;
| | - Junaid Ansari
- Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA;
| | - Stefan Reuter
- Division of General Internal Medicine, Nephrology and Rheumatology, Department of Medicine D, University Hospital of Münster, 48149 Münster, Germany;
| | - Benjamin Strücker
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, 48149 Münster, Germany; (F.B.); (L.K.); (C.R.); (A.M.); (B.S.); (A.P.); (J.G.B.)
| | - Andreas Pascher
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, 48149 Münster, Germany; (F.B.); (L.K.); (C.R.); (A.M.); (B.S.); (A.P.); (J.G.B.)
| | - Jens G. Brockmann
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, 48149 Münster, Germany; (F.B.); (L.K.); (C.R.); (A.M.); (B.S.); (A.P.); (J.G.B.)
| | | | - J. Steve Alexander
- Department of Neurology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA;
- Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA
- Correspondence: (J.S.A.); (F.N.E.G.)
| | - Felicity N. E. Gavins
- Department of Life Sciences, Centre for Inflammation Research and Translational Medicine (CIRTM), Brunel University London, Uxbridge UB8 3PH, UK
- Correspondence: (J.S.A.); (F.N.E.G.)
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Donor-derived Cell-free DNA as a Graft Injury Marker Following Kidney Transplantation. Transplant Direct 2022; 8:e1301. [PMID: 35368988 PMCID: PMC8966958 DOI: 10.1097/txd.0000000000001301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 01/18/2022] [Accepted: 01/22/2022] [Indexed: 12/02/2022] Open
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Coca A, Arias-Cabrales C, Pérez-Sáez MJ, Fidalgo V, González P, Acosta-Ochoa I, Lorenzo A, Rollán MJ, Mendiluce A, Crespo M, Pascual J, Bustamante-Munguira J. Impact of intra-abdominal pressure on early kidney transplant outcomes. Sci Rep 2022; 12:2257. [PMID: 35145181 PMCID: PMC8831606 DOI: 10.1038/s41598-022-06268-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Accepted: 01/06/2022] [Indexed: 12/13/2022] Open
Abstract
Increased intra-abdominal pressure (IAP) is common among post-surgical patients and may cause organ dysfunction. However, its impact after kidney transplantation on early postoperative complications and graft recovery remains unclear. We designed a prospective, observational cohort study to describe the prevalence and determinants of IAP, as well as its effect on delayed graft function, postoperative complications, and graft recovery. IAP was measured in 205 kidney transplant recipients every 8 h during the first 72 h after surgery using the urinary bladder technique. Intra-abdominal hypertension was defined as IAP ≥ 12 mmHg. Patients were followed for 6 months or until graft failure/death. Mean IAP was 12 ± 3.3 mmHg within the first 24 h. 78% of subjects presented with intra-abdominal hypertension during the first 72 h. Increased IAP was associated with higher renal resistive index [r = 0.213; P = 0.003] and lower urine output [r = - 0.237; P < 0.001]. 72 h mean IAP was an independent risk factor for delayed graft function [OR: 1.31; 95% CI: 1.13-1.51], postoperative complications [OR: 1.17; 95% CI: 1.03-1.33], and absence of graft function recovery [HR for graft function recovery: 0.94; 95% CI: 0.88-0.99]. Increased IAP was highly prevalent after transplantation and was independently associated with delayed graft function, postoperative complications, and absence of graft function recovery. Routine IAP monitoring should be considered post-transplantation to facilitate early recognition of relevant complications.
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Affiliation(s)
- Armando Coca
- Department of Nephrology, Hospital Clínico Universitario, Avda. Ramón y Cajal 3, 47003, Valladolid, Spain.
| | - Carlos Arias-Cabrales
- Department of Nephrology, Hospital del Mar, Paseo Marítimo de la Barceloneta 25-29, 08003, Barcelona, Spain
| | - María José Pérez-Sáez
- Department of Nephrology, Hospital del Mar, Paseo Marítimo de la Barceloneta 25-29, 08003, Barcelona, Spain
| | - Verónica Fidalgo
- Department of Nephrology, Hospital General, C/ Luis Erik Clavería Neurólogo s/n, 40002, Segovia, Spain
| | - Pablo González
- Department of Nephrology, Hospital Clínico Universitario, Avda. Ramón y Cajal 3, 47003, Valladolid, Spain
| | - Isabel Acosta-Ochoa
- Department of Nephrology, Hospital Clínico Universitario, Avda. Ramón y Cajal 3, 47003, Valladolid, Spain
| | - Arturo Lorenzo
- Department of Nephrology, Hospital Clínico Universitario, Avda. Ramón y Cajal 3, 47003, Valladolid, Spain
| | - María Jesús Rollán
- Department of Nephrology, Hospital Clínico Universitario, Avda. Ramón y Cajal 3, 47003, Valladolid, Spain
| | - Alicia Mendiluce
- Department of Nephrology, Hospital Clínico Universitario, Avda. Ramón y Cajal 3, 47003, Valladolid, Spain
| | - Marta Crespo
- Department of Nephrology, Hospital del Mar, Paseo Marítimo de la Barceloneta 25-29, 08003, Barcelona, Spain
| | - Julio Pascual
- Department of Nephrology, Hospital del Mar, Paseo Marítimo de la Barceloneta 25-29, 08003, Barcelona, Spain
| | - Juan Bustamante-Munguira
- Department of Cardiac Surgery, Hospital Clínico Universitario, Avda. Ramón y Cajal 3, 47003, Valladolid, Spain
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Aranda-Rivera AK, Srivastava A, Cruz-Gregorio A, Pedraza-Chaverri J, Mulay SR, Scholze A. Involvement of Inflammasome Components in Kidney Disease. Antioxidants (Basel) 2022; 11:246. [PMID: 35204131 PMCID: PMC8868482 DOI: 10.3390/antiox11020246] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/21/2022] [Accepted: 01/22/2022] [Indexed: 02/01/2023] Open
Abstract
Inflammasomes are multiprotein complexes with an important role in the innate immune response. Canonical activation of inflammasomes results in caspase-1 activation and maturation of cytokines interleukin-1β and -18. These cytokines can elicit their effects through receptor activation, both locally within a certain tissue and systemically. Animal models of kidney diseases have shown inflammasome involvement in inflammation, pyroptosis and fibrosis. In particular, the inflammasome component nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) and related canonical mechanisms have been investigated. However, it has become increasingly clear that other inflammasome components are also of importance in kidney disease. Moreover, it is becoming obvious that the range of molecular interaction partners of inflammasome components in kidney diseases is wide. This review provides insights into these current areas of research, with special emphasis on the interaction of inflammasome components and redox signalling, endoplasmic reticulum stress, and mitochondrial function. We present our findings separately for acute kidney injury and chronic kidney disease. As we strictly divided the results into preclinical and clinical data, this review enables comparison of results from those complementary research specialities. However, it also reveals that knowledge gaps exist, especially in clinical acute kidney injury inflammasome research. Furthermore, patient comorbidities and treatments seem important drivers of inflammasome component alterations in human kidney disease.
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Affiliation(s)
- Ana Karina Aranda-Rivera
- Laboratory F-315, Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City 04510, Mexico; (A.K.A.-R.); (A.C.-G.); (J.P.-C.)
| | - Anjali Srivastava
- Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India; (A.S.); (S.R.M.)
| | - Alfredo Cruz-Gregorio
- Laboratory F-315, Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City 04510, Mexico; (A.K.A.-R.); (A.C.-G.); (J.P.-C.)
| | - José Pedraza-Chaverri
- Laboratory F-315, Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico, Mexico City 04510, Mexico; (A.K.A.-R.); (A.C.-G.); (J.P.-C.)
| | - Shrikant R. Mulay
- Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow 226031, India; (A.S.); (S.R.M.)
| | - Alexandra Scholze
- Department of Nephrology, Odense University Hospital, Odense, Denmark, and Institute of Clinical Research, University of Southern Denmark, 5000 Odense C, Denmark
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48
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Eerhart MJ, Reyes JA, Blanton CL, Danobeitia JS, Chlebeck PJ, Zitur LJ, Springer M, Polyak E, Coonen J, Capuano S, D’Alessandro AM, Torrealba J, van Amersfoort E, Ponstein Y, Van Kooten C, Burlingham W, Sullivan J, Pozniak M, Zhong W, Yankol Y, Fernandez LA. Complement Blockade in Recipients Prevents Delayed Graft Function and Delays Antibody-mediated Rejection in a Nonhuman Primate Model of Kidney Transplantation. Transplantation 2022; 106:60-71. [PMID: 34905763 PMCID: PMC8674492 DOI: 10.1097/tp.0000000000003754] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND Complement activation in kidney transplantation is implicated in the pathogenesis of delayed graft function (DGF). This study evaluated the therapeutic efficacy of high-dose recombinant human C1 esterase inhibitor (rhC1INH) to prevent DGF in a nonhuman primate model of kidney transplantation after brain death and prolonged cold ischemia. METHODS Brain death donors underwent 20 h of conventional management. Procured kidneys were stored on ice for 44-48 h, then transplanted into ABO-compatible major histocompatibility complex-mismatched recipients. Recipients were treated with vehicle (n = 5) or rhC1INH 500 U/kg plus heparin 40 U/kg (n = 8) before reperfusion, 12 h, and 24 h posttransplant. Recipients were followed up for 120 d. RESULTS Of vehicle-treated recipients, 80% (4 of 5) developed DGF versus 12.5% (1 of 8) rhC1INH-treated recipients (P = 0.015). rhC1INH-treated recipients had faster creatinine recovery, superior urinary output, and reduced urinary neutrophil gelatinase-associated lipocalin and tissue inhibitor of metalloproteinases 2-insulin-like growth factor-binding protein 7 throughout the first week, indicating reduced allograft injury. Treated recipients presented lower postreperfusion plasma interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, and IL-18, lower day 4 monocyte chemoattractant protein 1, and trended toward lower C5. Treated recipients exhibited less C3b/C5b-9 deposition on day 7 biopsies. rhC1INH-treated animals also trended toward prolonged mediated rejection-free survival. CONCLUSIONS Our results recommend high-dose C1INH complement blockade in transplant recipients as an effective strategy to reduce kidney injury and inflammation, prevent DGF, delay antibody-mediated rejection development, and improve transplant outcomes.
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Affiliation(s)
- Michael J. Eerhart
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Jose A. Reyes
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
- Department of Surgery, New York Medical College at Metropolitan Hospital Center, New York, NY, United States
| | - Casi L. Blanton
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Juan S. Danobeitia
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Peter J. Chlebeck
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Laura J. Zitur
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Megan Springer
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Erzsebet Polyak
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Jennifer Coonen
- Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, United States
| | - Saverio Capuano
- Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, United States
| | - Anthony M. D’Alessandro
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Jose Torrealba
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States
| | | | | | - Cees Van Kooten
- Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - William Burlingham
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Jeremy Sullivan
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Myron Pozniak
- Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Weixiong Zhong
- Department of Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Yucel Yankol
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
| | - Luis A. Fernandez
- Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
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Chimerism and tolerance: past, present and future strategies to prolong renal allograft survival. Curr Opin Nephrol Hypertens 2021; 30:63-74. [PMID: 33186221 DOI: 10.1097/mnh.0000000000000666] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
PURPOSE OF REVIEW Immunological factors are a major cause of kidney allograft loss. Calcineurin inhibitors (CNIs) have improved short-term kidney allograft survival; however, they in turn contribute to long-term kidney allograft loss from chronic CNI nephrotoxicity. Tolerance induction in transplantation can avoid the long-term adverse effects of immunosuppressive medications. This review aims to critically discuss recent efforts in inducing transplantation tolerance. RECENT FINDINGS Tolerance induction mediated by chimerism has shown some promise in minimizing or even complete withdrawal of immunosuppressive treatments in kidney allograft recipients. There has been a number of approaches as varied as the number of centres conducting these trials. However, they can be grouped into those mediated by transient microchimerism and those facilitated by more stable macro or full donor chimerism. The success rates in terms of long-term drug-free graft survival has been limited in microchimerism-mediated tolerance induction approaches. Mixed macrochimerism of less than 50% donor may be unstable with mostly the recipient's native immune system overpowering the donor chimeric status.Tolerance induction leading to chimerism has been limited to living donor kidney transplantation and additional long-term outcomes are required. Furthermore, immune monitoring after tolerance induction has faced a limitation in studying due to a lack of sufficient study participants and appropriate study controls. SUMMARY Tolerance induction is one of several strategies used to prolong kidney allograft survival, but it has not been routinely utilized in clinical practice. However, future applications from the trials to clinical practice remain limited to living donor kidney transplantation. Once further data regarding tolerance inductions exist and practicality becomes widely accepted, tolerance induction may shift the paradigm in the field of kidney transplantation to achieve the best possible outcome of 'One Organ for Life'.
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Artificial Intelligence-A Tool for Risk Assessment of Delayed-Graft Function in Kidney Transplant. J Clin Med 2021; 10:jcm10225244. [PMID: 34830526 PMCID: PMC8618905 DOI: 10.3390/jcm10225244] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/02/2021] [Accepted: 11/10/2021] [Indexed: 11/17/2022] Open
Abstract
Delayed-graft function (DGF) might be responsible for shorter graft survival. Therefore, a clinical tool predicting its occurrence is vital for the risk assessment of transplant outcomes. In a single-center study, we conducted data mining and machine learning experiments, resulting in DGF predictive models based on random forest classifiers (RF) and an artificial neural network called multi-layer perceptron (MLP). All designed models had four common input parameters, determining the best accuracy and discriminant ability: donor’s eGFR, recipient’s BMI, donor’s BMI, and recipient–donor weight difference. RF and MLP designs, using these parameters, achieved an accuracy of 84.38% and an area under curve (AUC) 0.84. The model additionally implementing a donor’s age, gender, and Kidney Donor Profile Index (KDPI) accomplished an accuracy of 93.75% and an AUC of 0.91. The other configuration with the estimated post-transplant survival (EPTS) and the kidney donor risk profile (KDRI) achieved an accuracy of 93.75% and an AUC of 0.92. Using machine learning, we were able to assess the risk of DGF in recipients after kidney transplant from a deceased donor. Our solution is scalable and can be improved during subsequent transplants. Based on the new data, the models can achieve better outcomes.
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