scholarly journals Mesenchymal Stromal Cell Treatment of Kidneys During Normothermic Machine Perfusion is Safe and Feasible with Effective Traceability after Transplantation

2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Kaithlyn Rozenberg ◽  
Et al.
Keyword(s):  
The Netherlands ◽  
Clinical Medicine ◽  
Medical Center ◽  
Graft Function ◽  
University Hospital ◽  
Control Group ◽  
Machine Perfusion ◽  
Contralateral Kidney ◽  
Post Transplant ◽  
Normothermic Machine Perfusion

Lohmann 1/M. Pool 2, K. Rozenberg 3, M. Eijken 4, U. Møldrup 5, B.K. Møller 6, J.M. Sierra Parraga 7, M. Hoogduijn 7, L. Lo Faro 3, C. Moers 2, J. Hunter 3, A.K. Keller 1, H. Leuvenink 2, C.C. Baan 7, R.J. Ploeg 3, B. Jespersen 1 Department of Clinical Medicine, Aarhus University, Aarhus, Denmark Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark Department of Urology, Aarhus University Hospital, Aarhus, Denmark Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center, Rotterdam, the Netherlands Introduction Marginal kidneys are increasingly being accepted to decrease waiting time for a transplant. Normothermic machine perfusion (NMP) is a technique that allows delivery of therapies that may help condition or repair the organ prior to transplantation. Mesenchymal stromal cells (MSC) may be able to ameliorate ischaemia reperfusion injury as they possess potent anti-inflammatory and regenerative properties. We investigated the safety and effect of MSCs administered during ex vivo NMP prior to transplantation in a pig auto-transplant model of donation after circulatory death. Methods  Porcine kidneys subjected to 75 min warm ischaemia were retrieved and preserved for 14h by oxygenated HMP (oxHMP) and 4h NMP and then auto-transplantation. Kidneys were randomised to three different intervention strategies (n=7 per group): following 1h NMP, either a vehicle (NMP), 10 million pig MSC (NMP+pMSC) or 10 million human MSC (NMP+hMSC) were intra-arterially infused. The NMP groups were all compared to a control group, where kidneys were only preserved with oxHMP. The pig was re-anaesthetised, the contralateral kidney was removed and the treated kidney was auto-transplanted and the animals were recovered for 14 days. Results Renal blood flow during NMP was no different between the groups (p=0.0685). Post-transplant plasma creatinine increased in all groups but there were no significant differences between the groups (p=0.517). Plasma kidney injury biomarker NGAL was significantly higher in the NMP+pMSC group compared to the NMP (p=0.003) and NMP+hMSC (p=0.017) groups at day 14. On day 14, mGFR significantly improved in the NMP group compared to the control (55 ± 3 vs 42 ± 12 ml/min, p=0.025). No differences in GFR were observed on day 14 in the other groups (NMP+pMSC, p=0.090 and NMP+hMSC, p=0.387). MSC were detectable in biopsies of MSC treated kidney after NMP and post-transplantation. Conclusion NMP alone improved renal graft function compared to oxHMP of DCD kidneys post-transplant. The method of MSC administration during NMP proved to be safe, however in this model MSC treatment did not improve renal function. Nevertheless viable MSC remained detectable in the transplanted kidney at postoperative day 14 which may have an effect on longer term outcomes.

scholarly journals A Prospective Controlled Trial to Evaluate Safety and Efficacy of in vitro Expanded Recipient Regulatory T Cell Therapy and Tocilizumab Together With Donor Bone Marrow Infusion in HLA-Mismatched Living Donor Kidney Transplant Recipients (Trex001)

2021 ◽  
Vol 7 ◽  
Author(s):  
Rainer Oberbauer ◽  
Matthias Edinger ◽  
Gabriela Berlakovich ◽  
Peter Kalhs ◽  
Nina Worel ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Kidney Transplant ◽  
Graft Function ◽  
Control Group ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Post Transplant ◽  
Donor Bone Marrow ◽  
Living Donor Kidney Transplant

Background: The induction of donor-specific immunological tolerance could improve outcome after kidney transplantation. However, no tolerance protocol is available for routine clinical use. Chimerism-based regimens hold promise, but their widespread application is impeded in part by unresolved safety issues. This study tests the hypothesis that therapy with polyclonal recipient regulatory T cells (Tregs) and anti-IL6R (tocilizumab) leads to transient chimerism and achieves pro-tolerogenic immunomodulation in kidney transplant recipients also receiving donor bone marrow (BM) without myelosuppressive conditioning of the recipient.Methods/design: A prospective, open-label, controlled, single-center, phase I/IIa academic study is performed in HLA-mismatched living donor kidney transplant recipients.Study group: Recipients of the study group receive in vitro expanded recipient Tregs and a donor bone marrow cell infusion within 3 days after transplantation and tocilizumab for the first 3 weeks post-transplant. In addition they are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Starting 6 months post-transplant, sirolimus and steroids are withdrawn in a step-wise manner in stable patients.Control group: Recipients of the control group are treated with thymoglobulin, belatacept, sirolimus, and steroids as immunosuppression. Co-primary endpoints of safety (impaired graft function [eGFR <35 mL/min/1.73 m2], graft-vs.-host disease or patient death by 12 months) and efficacy (total leukocyte donor chimerism within 28 days post-transplant) are assessed. Secondary endpoints include frequency of biopsy-proven acute rejection episodes and subclinical rejection episodes on surveillance biopsies, assessment of kidney graft function, and the evaluation whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation.Discussion: The results of this trial will provide evidence whether treatment with recipient Tregs and donor BM is feasible, safe and efficacious in leading to transient chimerism. If successful, this combination cell therapy has the potential to become a novel treatment option for immunomodulation in organ transplantation without the toxicities associated with myelosuppressive recipient conditioning.Trial registration: European Clinical Trials Database EudraCT Nr 2018-003142-16 and clinicaltrials.gov NCT03867617.

scholarly journals 2659. Retrospective Review of Biopsy Proven Acute Graft Pyelonephritis in Renal Transplant Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S930-S930
Author(s):  
Harry Ross Powers ◽  
Walter Hellinger ◽  
Cherise Cortese ◽  
Hani M Wadei
Keyword(s):  
Risk Factors ◽  
Acute Rejection ◽  
Serum Creatinine ◽  
Potential Risk ◽  
Medical Center ◽  
Graft Function ◽  
Post Transplant ◽  
Histologic Evidence ◽  
Potential Risk Factors ◽  
Acute Graft

Abstract Background There are few studies of histologic acute graft pyelonephritis (HAGPN) following kidney transplant (KT). The goals of this study are to determine incidence, identify potential risk factors and describe outcomes of HAGPN in a large cohort of KT recipients. Methods Renal allograft biopsies of all patients undergoing first KT at our medical center between 2008 and 2017 were reviewed. HAGPN was defined as the presence of neutrophils within the interstitium and tubules (casts). Medical charts of patients with HAGPN were reviewed. Episodes of bacteriuria (≥10:5 cfu/mL growth in culture) were classified as urinary tract infection (UTI) or asymptomatic bacteruria (ASB) based upon documented symptoms. An episode of acute rejection was defined as pulse parenteral immunosuppressive therapy for histologic evidence of rejection. Results HAGPN was identified in 43 of 1,391 (3.1%) KT recipients at a median of 298 days post-transplant. There were no significant differences between recipient age or gender, donor age or transplant type (deceased, living related, living unrelated) between recipients with and without HAGPN. Urologic malformation was diagnosed in 14 (33%) by day 30 post-transplant. Twenty-five (58%), 17 (40%), and 13 (30%) sustained one or more episodes of acute rejection, UTI and ASB, respectively, prior to HAGPN. At diagnosis of HAGPN, 28 (65%), 7 (16%), and 16 (37%) had histologic evidence of rejection, UTI and ASB, respectively. Twenty-two (51%) and 37 (86%) were treated with pulse immunosuppression and antibiotics, respectively. Median nadir serum creatinine before HAGPN was 1.1 mg/day while median serum creatinine at 6 and 12 months after HAGPN were 1.5 and 1.6. Three patients (7%) developed graft failure within 1 year after HAGPN. Conclusion HAGPN is an infrequent complication of KT. A majority of patients with HAGPN have histologic evidence of rejection and either UTI or ASB at diagnosis, though over 40% have neither UTI nor ASB. When rejection accompanying HAGPN is routinely treated with pulse immunosuppression and antibiotic therapy is administered, graft function is preserved for most patients but a minority (7%) loses graft function within 1 year. Potential risk factors to be assessed in further study include post-transplant urologic dysfunction, acute rejection and UTI. Disclosures All authors: No reported disclosures.

Effect of Pre-Transplant Dialysis Modality on Kidney Transplantation Outcome

2009 ◽  
Vol 29 (2_suppl) ◽  
pp. 117-122 ◽  
Author(s):  
Yasar Caliskan ◽  
Halil Yazici ◽  
Numan Gorgulu ◽  
Berna Yelken ◽  
Turker Emre ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Acute Rejection ◽  
Bacterial Infections ◽  
Graft Function ◽  
Human Leukocyte ◽  
Control Group ◽  
Dialysis Modality ◽  
Post Transplant ◽  
Early Graft ◽  
Cmv Disease

Background The effect of pre-transplant dialysis modality on early graft function is a matter of debate. Although some authors deny the existence of a significant influence, others suggest that peritoneal dialysis (PD) affects early graft function favorably, possibly by contributing to a more physiologic water balance. In the present study, we evaluated the influence of pre-transplant dialysis modality on early and late graft function. Patients and Methods We studied 745 patients who underwent a first renal transplantation during 1983 – 2006, comparing the records of 44 PD patients [26 male; mean age: 26 ± 9 years (range: 8 – 56 years)] who received 36 living related and 8 cadaveric renal transplantations with those of a control group of 44 consecutive hemodialysis (HD) patients [26 male; mean age: 27 ± 11 years (range: 7 – 49 years)] for the index cases. Results The groups showed no significant differences in donor type, human leukocyte antigen matching, immunosuppressive protocols, and duration of dialysis. Also, neither group differed significantly with regard to incidence of delayed graft function, acute tubular necrosis, wound infection, systemic viral and bacterial infections, or acute rejection in the early post-transplant period. In the late post-transplant period, incidences of chronic rejection, graft failure, and malignancies were also similar. During the follow-up period, 3 patients in the PD group experienced acute rejection, 2 developed cytomegalovirus (CMV) disease, and 5 developed various other infections. In the HD group, 4 patients experienced acute rejection, 1 developed CMV disease, and 8 experienced other infections. Five patients in the PD group and one in the HD group died with functioning grafts ( p = 0.09). No differences were noted between the groups in the incidences of post-transplant cardiovascular complications, malignancies, and diabetes mellitus. In the PD group, 33 patients with functioning grafts are still being followed, 6 have returned to dialysis, and 5 have died. In the HD group, 38 patients with functioning grafts are still being followed, 5 have returned to dialysis, and 1 has died. Conclusions As a pre-transplant dialysis modality, neither HD nor PD affects the outcome of renal transplantation.

scholarly journals Delayed Renal Graft Function in the Early Post-Transplant Period and its Impact on the Late Post-Transplant Results

2013 ◽  
Vol 67 (1) ◽  
pp. 19-23
Author(s):  
Jānis Jušinskis ◽  
Diāna Amerika ◽  
Aleksandrs Maļcevs
Keyword(s):  
Negative Impact ◽  
Graft Function ◽  
Deceased Donor ◽  
Late Results ◽  
Control Group ◽  
Post Transplantation ◽  
Post Transplant ◽  
Renal Graft ◽  
Renal Grafts ◽  
The Impact

Delayed renal graft function (DGF) is a frequent complication with negative impact on the course of early post-transplantation period. The data concerning the impact on the late results are contradictory. This study describes results of 5-year follow-up of 248 recipients after deceased donor renal transplantation. All patients were divided into two groups: with delayed graft function (DGF, n = 53) and immediate graft function, considered as the control group (IGF, n = 195). We evaluated factors that were associated with development of DGF and its impact on the survival of graft and recipient, and frequency of acute rejections and chronic dysfunctions. The rate of observed DGF was 21.4%. Its development was associated with the following factors: age of recipient and their weight, age of donor and their body mass index, high frequency of asystole/hypotension in donors prior to organ explantation (P < 0.05 for all), and longer time of cold ischemia (P = 0.058). The DGF group had higher rate of acute rejections (P < 0.001), and also lower 1.5 and 5-year graft survival and 1.5-year patient survival (P < 0.05 for all). The conclusion is that DGF has negative impact on the survival of renal grafts and patients, especially during the first 1.5 years after transplantation.

Improving Liver Graft Function Using CD47 Blockade in the Setting of Normothermic Machine Perfusion

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Sandra Garcia-Aroz ◽  
Min Xu ◽  
Ola Ahmed ◽  
Joshua Hollingshead ◽  
Xuanchuan Wang ◽  
...  
Keyword(s):  
Graft Function ◽  
Liver Graft ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

Surgically Curable Pulmonary Hypertension: A View From the Experts

2003 ◽  
Vol 2 (1) ◽  
pp. 21-25
Author(s):  
Victor F. Tapson ◽  
William Auger ◽  
Peter Fedullo ◽  
Eckhard Mayer ◽  
Christopher McGregor
Keyword(s):  
Thoracic Surgery ◽  
San Diego ◽  
Clinical Medicine ◽  
Medical Center ◽  
Associate Professor ◽  
University Of California ◽  
University Hospital ◽  
Duke University ◽  
Von Liebig ◽  
Surgery Department

Five physicians addressed important issues in the diagnosis and management of patients with pulmonary thromboembolic disease. The roundtable discussion was moderated by Victor F. Tapson, MD, Associate Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina, and included William Auger, MD, Professor of Clinical Medicine, University of California, San Diego, Medical Center, San Diego, California; Peter Fedullo, MD, Clinical Professor of Medicine, University of California, San Diego, Medical Center; Eckhard Mayer, MD, Professor of Thoracic Surgery, Department of Cardio-Thoracic Surgery, University Hospital, Mainz, Germany; and Christopher McGregor, MD, Professor of Surgery, Consultant in Cardio-Thoracic Surgery, and Director of the Mayo Clinic William J von Liebig Transplant Center, Rochester, Minnesota.

scholarly journals A proof of concept study on real-time LiMAx CYP1A2 liver function assessment of donor grafts during normothermic machine perfusion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ivo J. Schurink ◽  
Jubi E. de Haan ◽  
Jorke Willemse ◽  
Matteo Mueller ◽  
Michael Doukas ◽  
...  
Keyword(s):  
Liver Function ◽  
Breath Test ◽  
Ex Vivo ◽  
Graft Function ◽  
Inverse Correlation ◽  
Lactate Clearance ◽  
Liver Graft ◽  
Machine Perfusion ◽  
Reliable Parameter ◽  
Normothermic Machine Perfusion

AbstractNo single reliable parameter exists to assess liver graft function of extended criteria donors during ex-vivo normothermic machine perfusion (NMP). The liver maximum capacity (LiMAx) test is a clinically validated cytochromal breath test, measuring liver function based on 13CO2 production. As an innovative concept, we aimed to integrate the LiMAx breath test with NMP to assess organ function. Eleven human livers were perfused using NMP. After one hour of stabilization, LiMAx testing was performed. Injury markers (ALT, AST, miR-122, FMN, and Suzuki-score) and lactate clearance were measured and related to LiMAx values. LiMAx values ranged between 111 and 1838 µg/kg/h, and performing consecutive LiMAx tests during longer NMP was feasible. No correlation was found between LiMAx value and miR-122 and FMN levels in the perfusate. However, a significant inverse correlation was found between LiMAx value and histological injury (Suzuki-score, R = − 0.874, P < 0.001), AST (R = − 0.812, P = 0.004) and ALT (R = − 0.687, P = 0.028). Furthermore, a significant correlation was found with lactate clearance (R = 0.683, P = 0.043). We demonstrate, as proof of principle, that liver function during NMP can be quantified using the LiMAx test, illustrating a positive correlation with traditional injury markers. This new breath-test application separates livers with adequate cytochromal liver function from inadequate ones and may support decision-making in the safe utilization of extended criteria donor grafts.

scholarly journals Advances in Hypothermic and Normothermic Perfusion in Kidney Transplantation

2021 ◽  
Vol 2 (4) ◽  
pp. 460-477
Author(s):  
Thomas B. Smith ◽  
Michael L. Nicholson ◽  
Sarah A. Hosgood
Keyword(s):  
Kidney Transplantation ◽  
Beneficial Effect ◽  
Graft Function ◽  
Machine Perfusion ◽  
Normothermic Perfusion ◽  
Normothermic Machine Perfusion ◽  
Organ Quality ◽  
Early Graft ◽  
Kidney Perfusion ◽  
Prolong Graft Survival

Hypothermic and normothermic machine perfusion in kidney transplantation are purported to exert a beneficial effect on post-transplant outcomes compared to the traditionally used method of static cold storage. Kidney perfusion techniques provide a window for organ reconditioning and quality assessment. However, how best to deliver these preservation methods or improve organ quality has not yet been conclusively defined. This review summarises the promising advances in machine perfusion science in recent years, which have the potential to further improve early graft function and prolong graft survival.

scholarly journals Predictors of persistent post transplant hyperparathyroidism (HPTx)

2015 ◽  
Vol 18 (1) ◽  
pp. 12-15
Author(s):  
Luiz Roberto Sousa Ulisses ◽  
Leonardo Figueiredo Camargo ◽  
Marcos Vinícius de Sousa ◽  
Carla Feitosa do Vale ◽  
Gabriel Giollo Rivelli ◽  
...  
Keyword(s):  
Mineral Metabolism ◽  
Graft Function ◽  
Control Group ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Inclusion Criteria ◽  
Post Transplant ◽  
Persistent Hyperparathyroidism ◽  
Serum Pth ◽  
Transplant Complications

Post transplant persistent Hyperparathyroidism (HPTx) increases the risk for transplant complications. Purpose: to identify risk factors for HPTx in the first post transplant year. Methods: Retrospective analysis of medical records from renal transplant recipients from July/2008 to December/2010. Inclusion criteria: serum PTH ≥500 pg/ml at transplant and normal 1-year graft function (serum creatinine ≤ 2mg/dL). From a group of 224 renal transplants, 69 (30%) fulfilled the inclusion criteria, and they were divided in 2 groups, according to the serum PTH after 1 year of transplant: control, 1-year P TH<150 p g/ml ( n=32) a nd P ersistent H yperparathyroidism, H PTx, 1 -year P TH ≥ 1 50 p g/ml ( n= 3 7). Data analyzed: serum calcium (Ca), phosphate (Pi), alkaline phosphatase (AP), PTH and glomerular filtration rate (GFR) at transplant, and 3, 6 and 12 months post transplant. Results: At transplant, the groups were comparable as to age, Pi and PTH. However, the length of the dialysis (78 40 vs. 50 34 months, p<0.05) and Ca (8,9 0.9 vs. 8,5 0,6mg/dL, p<0.05) were higher in the HPTx group. After 3 months post transplant, HPTx group maintained higher PTH levels (365.4 176.2 vs. 166.9 92.2pg/mL, p<0.05), and AP (175 145 vs. 109 52UI, p<0.05), than controls, despite of the comparable Ca, Pi, and GFR. From the 6th post transplant month, the HPTx group persisted with hypercalcemia (10.2 0.7 vs. 9.9 0.5mg/dL, p<0.05) and low phosphate (2.6 0.5 vs. 2.9 0.7, p<0.05) with higher AP and PTH levels than in controls (p<0.05). At the end of the 1 post transplant year, HPTx group persisted with hypercalcemia, despite the recovery of the graft function while in the control group, the GFR recovery was associated with normalization of the bone mineral metabolism parameters. Conclusion: HPTx was associated with longer pre transplant dialysis therapy and higher Ca at transplant. Higher PTH and AP post transplant levels at the 3rd month were associated with persistent hyperparathyroidism, as well as persistent hypercalcemia and low phosphate, despite of the GFR recovery.

Sign in / Sign up

Export Citation Format

Share Document