Effect of the Brain-Death Process on Acute Rejection in Renal Transplantation

Sánchez‐Fructuoso, Ana; García, Pablo Naranjo; Romero, Natividad Calvo; Ridao, N.; Gómez, P. Naranjo; Conesa, J.; Barrientos, Alberto

doi:10.1016/j.transproceed.2007.07.044

Cited by 15 publications

(11 citation statements)

References 5 publications

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“…The physiological changes that occur after BD include hemodynamic changes, blood coagulation, endocrine and/or electrolyte disorders. Several studies have shown that grafts from BD donors have a lower short- and long-term posttranslational effectiveness and higher incidences of primary graft non-function [37] and higher incident of acute rejection [38], in comparison with that from living donors. Despite these crucial observations, the exact etiology of the poor quality of donor-liver function has not been fully examined.…”

Section: Discussionmentioning

confidence: 99%

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PP2Ac upregulates PI3K-Akt signaling and induces hepatocyte apoptosis in liver donor after brain death

et al. 2019

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Multiple research groups have demonstrated that the outcome of patients receiving liver grafts from brain death donors (DBD) is poorer when compared with patients receiving grafts from living donors. This might be due to an increased hepatocyte apoptosis induced after brain death (BD). In this work, we found that the activity of PP2A-Akt pathway is significantly increased in clinical donor ex vivo hepatocytes after BD by iTRAQ protein quantification analysis. The same results were confirmed in animal models. A time-dependent promotion of apoptosis was also found in DBD rabbit liver, as demonstrated by the increased levels of cleaved Caspase 3 and the decreased of Bcl-2. To further investigate the roles of PP2A and Akt in regulating apoptosis of hepatocytes after BD, we cultivated human liver cell line L02 with serum deprivation and hypoxia, to simulate the ischemic and hypoxic conditions of hepatocytes in DBD. Increased apoptosis and decreased viability were observed during the time in this model. Meanwhile PP2A activity and Akt activity were respectively increased and decreased. Notably, the proportion of Akt phosphorylation at Ser473 decreased, while other known targets of PP2A (p38, JNK and ERK) were not affected in terms of protein levels or phosphorylation. These results suggested that PP2A is involved in apoptotic induction of hepatocytes after brain death by specific suppression of Akt. This discovery was further confirmed with pharmaceutical and genetic methods. Our work implied potential targets for reducing liver cell apoptosis and improving organ donor quality after BD.Electronic supplementary materialThe online version of this article (10.1007/s10495-019-01570-8) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

“…Brain death can change the inflammation response, which releases inflammatory mediators and promotes apoptosis [5]. In addition, it can contribute directly to the activation of caspase 3 leading to apoptosis [38]. HO-1, which has strong anti-oxidant activity, can improve long-term brain dead graft survival [40].…”

Section: Discussionmentioning

confidence: 99%

PP2Ac upregulates PI3K-Akt signaling and induces hepatocyte apoptosis in liver donor after brain death

et al. 2019

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“…Apparently, the immune system of recipients with higher sCD30 is more activated [29]; hence, patients are prone to reject more immunogenic graft of inferior quality, which is typical for cadaver kidney [37]. Prognostic role of sCD30 for AR was established earlier in several studies of cadaver kidney transplantation [4, 11], including large multicenter trials [9, 10, 14].…”

Section: Discussionmentioning

confidence: 99%

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients’ Survival

Trailin

Ostapenko²,

Nykonenko

et al. 2017

Disease Markers

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Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

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“…The immunologic consequences of brain death, relevant to clinical transplantation, can be viewed in terms of systemic and organ-specific effects. Changes in IL-1, IL-6, TNF-a, ICAM-1, VCAM-1 and numerous other inflammatory products have been documented (2,(15)(16)(17)(18). Despite subtle differences among different experimental models, it is readily apparent that brain death results in significant changes in the expression of cytokines, cellular adhesion molecules and inflammatory cell products.…”

Section: Discussionmentioning

confidence: 99%

Donor Brain Death Inhibits Tolerance Induction in Miniature Swine Recipients of Fully MHC-Disparate Pulmonary Allografts

Meltzer

Veillette

Aoyama

et al. 2012

American Journal of Transplantation

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We have previously shown that a short course of high-dose tacrolimus induces long-term tolerance to fully mismatched lung allografts procured from healthy MHC-inbred miniature swine. Here, we investigate whether donor brain death affects tolerance induction. Four recipient swine were transplanted with fully mismatched lung grafts from donors that were rendered brain dead and mechanically ventilated for 4 h before procurement (Group 1). These recipients were compared to two control groups (Group 2: 4 h of donor ventilation without brain death [n = 5]; and Group 3: no donor brain death with <1 h of ventilation [n = 6]). All recipients were treated with a 12-day course of tacrolimus. In contrast to both groups of control animals, the swine transplanted with lung allografts from brain dead donors all rejected their grafts by postoperative day 45 and showed persistent responsiveness to donor antigen by MLR. Several additional swine underwent brain death induction and/or mechanical ventilation alone to determine the effects of these procedures on the expression of proinflammatory molecules. Significant increases in serum concentrations of IL-1, TNF-α and IL-10 were seen after brain death. Upregulation of IL-1 and IL-6 gene expression was also observed.

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Effect of the Brain-Death Process on Acute Rejection in Renal Transplantation

Cited by 15 publications

References 5 publications

PP2Ac upregulates PI3K-Akt signaling and induces hepatocyte apoptosis in liver donor after brain death

PP2Ac upregulates PI3K-Akt signaling and induces hepatocyte apoptosis in liver donor after brain death

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients’ Survival

Donor Brain Death Inhibits Tolerance Induction in Miniature Swine Recipients of Fully MHC-Disparate Pulmonary Allografts

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