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 Viktor; Günther, Julia; Hofhansel, Lena; Kühl, Anja A.; Sattler, Arne; Ernst, Stefanie; Friedersdorff, Frank; Ebner, Susanne; Weiß, Sascha; Bösmüller, Claudia; Weißenbacher, Annemarie; Oberhuber, Rupert; Cardini, Benno; Öllinger, Robert; Schneeberger, Stefan; Biebl, Matthias; Denecke, Christian; Margreiter, Christian; Resch, Thomas; Aigner, Felix; Maglione, Manuel; Pratschke, Johann; Kotsch, Katja

doi:10.3389/fimmu.2018.01911

Cited by 6 publications

(13 citation statements)

References 50 publications

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“…For example, etanercept, a TNFα inhibitor, has been administered ex vivo under machine perfusion hypothermia conditions in kidney transplant recipients, with no differences in DGF and graft survival between groups [88]. A recent study by Ritschl et al [89] explored the effect of perioperative perfusion of extended-criteria kidney allografts with anti-T lymphocyte globulin (ATG), which is used routinely as induction therapy to prevent graft rejection, and the results demonstrated a reduction of DGF and the need for dialysis in the short term, but no therapeutic effect was observed at 1-year follow-up.…”

Section: Organ Recovery and Processingmentioning

confidence: 99%

Review: Ischemia Reperfusion Injury—A Translational Perspective in Organ Transplantation

Fernández

Sánchez-Tarjuelo

Cravedi

et al. 2020

IJMS

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Thanks to the development of new, more potent and selective immunosuppressive drugs together with advances in surgical techniques, organ transplantation has emerged from an experimental surgery over fifty years ago to being the treatment of choice for many end-stage organ diseases, with over 139,000 organ transplants performed worldwide in 2019. Inherent to the transplantation procedure is the fact that the donor organ is subjected to blood flow cessation and ischemia during harvesting, which is followed by preservation and reperfusion of the organ once transplanted into the recipient. Consequently, ischemia/reperfusion induces a significant injury to the graft with activation of the immune response in the recipient and deleterious effect on the graft. The purpose of this review is to discuss and shed new light on the pathways involved in ischemia/reperfusion injury (IRI) that act at different stages during the donation process, surgery, and immediate post-transplant period. Here, we present strategies that combine various treatments targeted at different mechanistic pathways during several time points to prevent graft loss secondary to the inflammation caused by IRI.

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Section: Organ Recovery and Processingmentioning

confidence: 99%

Review: Ischemia Reperfusion Injury—A Translational Perspective in Organ Transplantation

Fernández

Sánchez-Tarjuelo

Cravedi

et al. 2020

IJMS

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“…Endpoints were defined similarly to our previously published trial [31]. The primary endpoint was defined as a change in graft function at day 7 from baseline, defined by the assessment of AST.…”

Section: Endpointsmentioning

confidence: 99%

“…Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed as recently described [31,32]. In brief, total RNA from snap-frozen biopsies was extracted using the NucleoSpin RNA Kit (Macherey-Nagel, Düren, Germany) according to the manufacturer's instructions.…”

Section: Real-time Rt-pcrmentioning

confidence: 99%

“…In a recently published RCT, we demonstrated that the perioperative perfusion of kidneys with ATLG prior to transplantation could significantly improve short-term outcomes [31]. Complementary to this successful trial, we performed a prospective, singlecenter, single-blinded, placebo-controlled RCT in livers to delineate whether perioperative ATLG-graft perfusion can ameliorate IRI also in the setting of LTx.…”

Section: Introductionmentioning

confidence: 98%

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Perioperative Perfusion of Allografts with Anti-Human T-lymphocyte Globulin Does Not Improve Outcome Post Liver Transplantation—A Randomized Placebo-Controlled Trial

Ritschl

Günther

Hofhansel

et al. 2021

JCM

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Due to the lack of suitable organs transplant surgeons have to accept unfavorable extended criteria donor (ECD) organs. Recently, we demonstrated that the perfusion of kidney organs with anti-human T-lymphocyte globulin (ATLG) prior to transplantation ameliorates ischemia-reperfusion injury (IRI). Here, we report on the results of perioperative ATLG perfusion in a randomized, single-blinded, placebo-controlled, feasibility trial (RCT) involving 30 liver recipients (LTx). Organs were randomly assigned for perfusion with ATLG/Grafalon® (AP) (n = 16) or saline only (control perfusion = CP) (n = 14) prior to implantation. The primary endpoint was defined as graft function reflected by aspartate transaminase (AST) values at day 7 post-transplantation (post-tx). With respect to the primary endpoint, no significant differences in AST levels were shown in the intervention group at day 7 (AP: 53.0 ± 21.3 mg/dL, CP: 59.7 ± 59.2 mg/dL, p = 0.686). Similarly, exploratory analysis of secondary clinical outcomes (e.g., patient survival) and treatment-specific adverse events revealed no differences between the study groups. Among liver transplant recipients, pre-operative organ perfusion with ATLG did not improve short-term outcomes, compared to those who received placebo perfusion. However, ATLG perfusion of liver grafts was proven to be a safe procedure without the occurrence of relevant adverse events.

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“…Older donor organs have higher immunogenicity, mediated by poorer monocyte clearance of damaged necrotic cells, and therefore recipients may require a more intense immunosuppression in the early period after Tx (19)(20)(21)(22). Knowing about the ECD grafts' increased risk for poor function or failure (23)(24)(25), implementation of new storage techniques, such as MP, paved the way for better characterization of organ quality and the possibility for graft reconditioning before Tx to improve organ vulnerability and immunogenicity (10,26).…”

Section: Introductionmentioning

confidence: 99%

Machine Perfusion of Extended Criteria Donor Organs: Immunological Aspects

et al. 2020

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Due to higher vulnerability and immunogenicity of extended criteria donor (ECD) organs used for organ transplantation (Tx), the discovery of new treatment strategies, involving tissue allorecognition pathways, is important. The implementation of machine perfusion (MP) led to improved estimation of the organ quality and introduced the possibility to achieve graft reconditioning prior to Tx. A significant number of experimental and clinical trials demonstrated increasing support for MP as a promising method of ECD organ preservation compared to classical static cold storage. MP reduced ischemia-reperfusion injury resulting in the protection from inadequate activation of innate immunity. However, there are no general agreements on MP protocols, and clinical application is limited. The objective of this comprehensive review is to summarize literature on immunological effects of MP of ECD organs based on experimental studies and clinical trials.

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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

Cited by 6 publications

References 50 publications

Review: Ischemia Reperfusion Injury—A Translational Perspective in Organ Transplantation

Review: Ischemia Reperfusion Injury—A Translational Perspective in Organ Transplantation

Perioperative Perfusion of Allografts with Anti-Human T-lymphocyte Globulin Does Not Improve Outcome Post Liver Transplantation—A Randomized Placebo-Controlled Trial

Machine Perfusion of Extended Criteria Donor Organs: Immunological Aspects

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