Dataset Information

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period-a Prospective, Randomized Placebo-Controlled Trial.

ABSTRACT: Introduction: Although prone to a higher degree of ischemia reperfusion injury (IRI), the use of extended criteria donor (ECD) organs has become reality in transplantation. We therefore postulated that peri-operative perfusion of renal transplants with anti-human T-lymphocyte globulin (ATLG) ameliorates IRI and results in improved graft function. Methods: We performed a randomized, single-blinded, placebo-controlled trial involving 50 kidneys (KTx). Prior to implantation organs were perfused and incubated with ATLG (AP) (n = 24 kidney). Control organs (CP) were perfused with saline only (n = 26 kidney). Primary endpoint was defined as graft function reflected by serum creatinine at day 7 post transplantation (post-tx). Results: AP-KTx recipients illustrated significantly better graft function at day 7 post-tx as reflected by lower creatinine levels, whereas no treatment effect was observed after 12 months surveillance. During the early hospitalization phase, 16 of the 26 CP-KTx patients required dialysis during the first 7 days post-tx, whereas only 10 of the 24 AP-KTx patients underwent dialysis. No treatment-specific differences were detected for various lymphocytes subsets in the peripheral blood of patients. Additionally, mRNA analysis of 0-h biopsies post incubation with ATLG revealed no changes of intragraft inflammatory expression patterns between AP and CP organs. Conclusion: We here present the first clinical study on peri-operative organ perfusion with ATLG illustrating improved graft function in the early period post kidney transplantation. Clinical Trial Registration: www.ClinicalTrials.gov, NCT03377283.

SUBMITTER: Ritschl PV

PROVIDER: S-EPMC6117415 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period-a Prospective, Randomized Placebo-Controlled Trial.

Ritschl Paul V PV Günther Julia J Hofhansel Lena L Kühl Anja A AA Sattler Arne A Ernst Stefanie S Friedersdorff Frank F Ebner Susanne S Weiss Sascha S Bösmüller Claudia C Weissenbacher Annemarie A Oberhuber Rupert R Cardini Benno B Öllinger Robert R Schneeberger Stefan S Biebl Matthias M Denecke Christian C Margreiter Christian C Resch Thomas T Aigner Felix F Maglione Manuel M Pratschke Johann J Kotsch Katja K

Frontiers in immunology 20180824

<b>Introduction:</b> Although prone to a higher degree of ischemia reperfusion injury (IRI), the use of extended criteria donor (ECD) organs has become reality in transplantation. We therefore postulated that peri-operative perfusion of renal transplants with anti-human T-lymphocyte globulin (ATLG) ameliorates IRI and results in improved graft function. <b>Methods:</b> We performed a randomized, single-blinded, placebo-controlled trial involving 50 kidneys (KTx). Prior to implantation organs wer ...[more]

PMID: 30197644

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Project description:BackgroundRabbit-generated antithymocyte globulins (ATGs), which target human T cells, are widely used as immunosuppressive agents during treatment of kidney allograft recipients. However, ATGs can induce immune complex diseases, including serum sickness disease (SSD). Rabbit and human IgGs have various antigenic differences, including expression of the sialic acid Neu5Gc and ?-1-3-Gal (Gal), which are not synthesized by human beings. Moreover, anti-Neu5Gc antibodies have been shown to preexist and be elicited by immunization in human subjects. This study aimed to assess the effect of SSD on long-term kidney allograft outcome and to compare the immunization status of grafted patients presenting with SSD following ATG induction treatment.MethodsWe analyzed data from a cohort of 889 first kidney graft recipients with ATG induction (86 with SSD [SSD(+)] and 803 without SSD [SSD(-)]) from the Données Informatisées et Validées en Transplantation data bank. Two subgroups of SSD(+) and SSD(-) patients that had received ATG induction treatment were then assessed for total anti-ATG, anti-Neu5Gc, and anti-Gal antibodies using ELISA assays on sera before and after transplantation.ResultsSSD was significantly associated with long-term graft loss (>10 years, P = 0.02). Moreover, SSD(+) patients exhibited significantly elevated titers of anti-ATG (P = 0.043) and anti-Neu5Gc (P = 0.007) IgGs in late post-graft samples compared with SSD(-) recipients.ConclusionIn conclusion, our data indicate that SSD is a major contributing factor of late graft loss following ATG induction and that anti-Neu5Gc antibodies increase over time in SSD(+) patients.FundingThis study was funded by Société d'Accélération du Transfert de Technologies Ouest Valorisation, the European FP7 "Translink" research program, the French National Agency of Research, Labex Transplantex, the Natural Science and Engineering Research Council of Canada, and the Canadian Foundation for Innovation.

Project description:IntroductionAcute early vascular complications are rare, but serious complications after kidney transplantation. They often result in graft loss. For this reason, shortening the diagnostic process is crucial. Currently, it is standard procedure to monitor renal graft perfusion using Doppler ultrasound (DU). With respect to acute vascular complications, the main disadvantage of this type of examination is its periodicity. It would be of great benefit if graft blood perfusion could be monitored continuously during the early postoperative period. It appears evident that a well-designed near infrared spectroscopy (NIRS) monitoring system could prove very useful during the early post-transplantation period. Its role in the immediate diagnosis of vascular complications could result in a significant increase in graft salvage, thus improving the patient's overall quality of life and lowering morbidity and mortality for renal graft recipients. The aim of this study was to design, construct and test such a monitoring system.Materials and methodsWe designed a rough NIRS-based system prototype and prepared a two-stage laboratory experiment based on a laboratory pig model. In the first stage, a total of 10 animals were used to verify and optimize the technical aspects and functionality of the prototype sensor by testing it on the animal kidneys in-vivo. As a result of these tests, a more specific prototype was designed. During the second stage, we prepared a unique laboratory model of a pig kidney autotransplantation and tested the system for long-term functionality on a group of 20 animals. Overall sensitivity and specificity were calculated, and a final prototype was prepared and completed with its own analytic software and chassis.ResultsWe designed and constructed a NIRS-based system for kidney graft perfusion monitoring. The measurement system provided reliable performance and 100% sensitivity when detecting acute diminished blood perfusion of the transplanted kidneys in laboratory conditions.ConclusionThe system appears to be a useful tool for diagnosing diminished blood perfusion of kidney transplants during the early postoperative period. However, further testing is still required. We believe that applying our method in current human transplantation medicine is feasible, and we are confident that our prototype is ready for human testing.

Project description:Haploidentical hematopoietic stem cell transplantation (haploHSCT) with conditioning regimens using post-transplant cyclophosphamide (PTCy) for peripheral blood stem cell (PBSC) grafts is limited by comparably higher rates of acute and chronic graft-versus-host disease (GVHD). Antithymocyte globulin (ATG) may mitigate this risk. We evaluated haploHSCT after reduced-intensity conditioning (RIC) with ATG, PTCy, and cyclosporine to prevent rejection and GVHD. Fifty adults underwent haploHSCT from August 2016 to February 2018. RIC included fludarabine (30 mg/m2/day on days -5 to -2), busulfan (3.2 mg/m2/day on days -3 and -2), and total body irradiation (200 cGy) on day -1. Unmanipulated PBSCs were infused on day 0. GVHD prophylaxis included ATG (4.5 mg/kg over days -3 to -1), PTCy (50 mg/kg/day on days +3 and +4), and cyclosporine from day +5. Median age was 56 years (range, 22 to 70 years); 25 (73.5%) patients were in first complete remission (CR1), 5 (14.7%) were in second complete remission (CR2), and 8 (23.5%) had active disease. Median time to neutrophil engraftment was 16 days (range, 8 to 43 days). At day +100, the cumulative incidence of acute GVHD of any grade, and grades III to IV was 38.3% and 5.2%, respectively. Mild chronic GVHD was seen in 15.5%. Cytomegalovirus (CMV) reactivation occurred in 37 (74%) cases and CMV disease occurred in 4 (11.5%) cases. Epstein-Barr virus (EBV) reactivation occurred in 21 (61.8%) patients. The incidence of histologically confirmed post-transplantation lymphoproliferative disorder (PTLD) was 5.8%. Four patients received rituximab. There were no CMV, EBV, or PTLD-related deaths. Six-month and 1-year overall survival (OS), cumulative incidence of relapse (CIR), and nonrelapse mortality (NRM) were 73.9%, 10.2%, and 19.4%, respectively, and 48.1%, 16% and 38.2%, respectively. Infection was the most common cause of death (18%). Unmanipulated haploidentical PBSC transplantation following RIC with ATG, PTCy, and cyclosporine as a GVHD prevention strategy results in low rates of acute and chronic GVHD.

Dataset Information

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period-a Prospective, Randomized Placebo-Controlled Trial.

Publications

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period-a Prospective, Randomized Placebo-Controlled Trial.

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