The effect of the use of a TNF-alpha inhibitor in hypothermic machine perfusion on kidney function after transplantation

Diuwe, Piotr; Domagała, Piotr; Durlik, M.; Trzebicki, Janusz; Chmura, A.; Kwiatkowski, A.

doi:10.1016/j.cct.2017.05.013

Cited by 19 publications

(16 citation statements)

References 37 publications

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“…However, the role of TNFα-I in mitigating allograft rejection and IR injury is still unclear, and no significant differences in delayed graft function have been found with the use of TNFα-I therapy. 17 In the current study, no significant difference in rejection rates between cohorts was found, and the incidence of rejection overall was low.…”

Section: Discussioncontrasting

confidence: 53%

Management of Tumor Necrosis Factor α Inhibitor Therapy After Renal Transplantation: A Comparative Analysis and Associated Outcomes

et al. 2018

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Background: Biologic agents inhibiting the tumor necrosis factor α pathway (TNFα-Is) are used to treat systemic inflammatory diseases. The best management of these agents after renal transplantation is unknown. Objective: Evaluate peritransplant use of TNFα-Is and associated outcomes. Methods: Retrospective, single-center study of adult renal-transplant-recipients (RTRs) transplanted between 1/1/1998-12/31/2017, who received TNFα-Is for inflammatory disease prior to transplant. Qualifying patients were divided into 2 cohorts: patients who resumed TNFα-Is after transplant and those who did not. Outcomes were evaluated. Results: A total of 5256 renal transplants occurred in the study window; 14 patients met inclusion criteria. Primary indication for TNFα-I was Crohn’s-disease (CD; 57.1%). Infliximab was utilized most frequently (50%). Seven RTRs resumed TNFα-I posttransplant; mean time to resumption of 10.6±4.35 months (median=6 months), 85.7% for CD. Immunosuppression was modified in 2 patients (28.6%) in response to restarting TNFα-I therapy. Seven RTRs did not resume TNFα-Is following transplant; the majority of these had rheumatic diseases. There was no significant difference in time to first bacterial or fungal infection, rejection, or patient survival between the 2 groups. Last measured estimated glomerular-filtration-rate was similar between groups (TNFα-I: 41 ± 14.2 vs 48.6 ± 8.6, P = 0.25). No patient had cytomegalovirus infection; however, 42.8% of each cohort had documented BK virus infection. Malignancy occurred more frequently in the cohort that resumed TNFα-Is (42.8% vs 14.3%, P = 0.24); however, this was not statistically significant. Conclusion and Relevance: TNFα-I therapy prior to renal-transplant is relatively uncommon. The decision to continue therapy after transplant must balance risks of infection and malignancy against inflammatory disease recurrence. A multidisciplinary treatment approach is necessary as use of TNFα-I affects immunosuppressive management and appears to affect transplant outcomes. Future studies are needed to further clarify the role of TNFα-I therapy use in RTRs with inflammatory disorders focusing on its correlation with both BK and malignancy.

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Section: Discussioncontrasting

confidence: 53%

Management of Tumor Necrosis Factor α Inhibitor Therapy After Renal Transplantation: A Comparative Analysis and Associated Outcomes

et al. 2018

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“…First, the combination of machine perfusion and additional agents including antibodies or alternative therapeutics (48, 49) may provide a synergistic effect with regard to organ preservation and reduction of IRI. Second, consideration of the influence of age is strongly recommended for upcoming clinical trials.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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

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“…Of the clinical trials reported, only the administration of prostaglandin E 1 during HMP had any beneficial effect on improving graft function after transplantation yet this has not been used since [41]. None of the clinical studies have examined the effects of cellular‐ or genetic‐based therapies during HMP.…”

Section: Discussionmentioning

confidence: 99%

“…No significant differences in graft function up to 12 months were found compared to kidneys without tPA treatment. However, the study did demonstrate the feasibility of tPA treatment during HMP without complications [41] by eliminating the high risk of bleeding associated with the systemic administration of tPA. A possible explanation for the lack of effect is that the study did not include the addition of plasminogen to the perfusate during treatment with tPA.…”

Section: Clinical Trialsmentioning

confidence: 99%

Treatment of transplant kidneys during machine perfusion

2020

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Summary The increasing use of donation after circulatory death (DCD) and extended criteria donor (ECD) organs has raised awareness of the need to improve the quality of kidneys for transplantation. Treating kidneys during the preservation interval could improve early and long‐term graft function and survival. Dynamic modes of preservation including hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) may provide the functional platforms to treat these kidneys. Therapies in the field of regenerative medicine including cellular therapies and genetic modification and the application of biological agents targeting ischaemia reperfusion injury (IRI) and acute rejection are a growing area of research. This review reports on the application of cellular and gene manipulating therapies, nanoparticles, anti‐inflammatory agents, anti‐thrombolytic agents and monoclonal antibodies administered during HMP and NMP in experimental models. The review also reports on the clinical effectiveness of several biological agents administered during HMP. All of the experimental studies provide proof of principle that therapies can be successfully delivered during HMP and NMP. However, few have examined the effects after transplantation. Evidence for clinical application during HMP is sparse and only one study has demonstrated a beneficial effect on graft function. More investigation is needed to develop perfusion strategies and investigate the different experimental approaches.

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The effect of the use of a TNF-alpha inhibitor in hypothermic machine perfusion on kidney function after transplantation

Cited by 19 publications

References 37 publications

Management of Tumor Necrosis Factor α Inhibitor Therapy After Renal Transplantation: A Comparative Analysis and Associated Outcomes

Management of Tumor Necrosis Factor α Inhibitor Therapy After Renal Transplantation: A Comparative Analysis and Associated Outcomes

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

Treatment of transplant kidneys during machine perfusion

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