Protective effect of immunosuppressive treatment before orthotopic kidney autotransplantation

Cicora, Federico; Lausada, Natalia; Vásquez, Daniela N.; Cicora, P.; Guerrieri, Diego; González, Pedro; Zalazar, Gustavo; Stringa, Pablo; Raimondi, C.

doi:10.1016/j.trim.2010.10.006

Cited by 11 publications

(42 citation statements)

References 46 publications

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“…44 Rapamycin is reported to cause both better and worse outcomes in rodent kidney IRI and transplantation models. [70][71][72][73][74][75] These effects are generally attributed to its antiproliferative properties, but it is unclear whether autophagy stimulation is also involved. The exact outcome also likely depends on the administered dose, 76 ischemic time, markers measured, and phase postreperfusion (Fig 4).…”

Section: Modulation Of Autophagy In Renal Iri With Diuretics and Immumentioning

confidence: 99%

Autophagy and the Kidney: Implications for Ischemia-Reperfusion Injury and Therapy

Decuypere

Ceulemans

Agostinis³

et al. 2015

American Journal of Kidney Diseases

116

100

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Section: Modulation Of Autophagy In Renal Iri With Diuretics and Immumentioning

confidence: 99%

Autophagy and the Kidney: Implications for Ischemia-Reperfusion Injury and Therapy

Decuypere

Ceulemans

Agostinis³

et al. 2015

American Journal of Kidney Diseases

116

100

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“…In contrast, studies examining effects of carcineurin inhibitors on renal I/R injury show contradictory results depending on the treatment protocols. Although brief administration of carcineurin inhibitors shows protective effects [47–49], prolonged use of these drugs, as well as rapamycin and MMF has been shown to increase renal injury, most likely because of their toxicity to kidneys and interference on repair process [50–52]. CO has been shown to exert protection against nephrotoxic side effects caused by cisplatin [53], and further studies are warranted to determine if CO can protect kidney grafts under immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

Carbon monoxide inhibits apoptosis during cold storage and protects kidney grafts donated after cardiac death

Ozaki

Yoshida

Ueki

et al. 2011

Transplant International

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Summary Ischemia/reperfusion (I/R) injury remains as a serious deleterious factor in kidney transplantation (KTx). We hypothesized that carbon monoxide (CO), an endogenous potent cytoprotective molecule, inhibits hypothermia‐induced apoptosis of kidney grafts. Using the rat KTx model mimicking the conditions of donation after cardiac death (DCD) as well as nontransplantable human kidney grafts, this study examined effects of CO in preservation solution in improving the quality of marginal kidney grafts. After cardiac cessation, rat kidneys underwent 40 min warm ischemia (WI) and 24 h cold storage (CS) in control UW or UW containing CO (CO‐UW). At the end of CS, kidney grafts in control UW markedly increased mitochondrial porin release into the cytosol and resulted in increased cleaved caspase‐3 and PARP expression. In contrast, grafts in CO‐UW had significantly reduced mitochondrial breakdown and caspase pathway activation. After KTx, recipient survival significantly improved with CO‐UW with less TUNEL+ cells and reduced mRNA upregulation for proinflammatory mediators (IL‐6, TNF‐α, iNOS). Furthermore, when nontransplantable human kidney grafts were stored in CO‐UW for 24 h, graft PARP expression, TUNEL+ cells, and proinflammatory mediators were less than those in control UW. CO in UW inhibited hypothermia‐induced apoptosis and significantly improved kidney graft function and outcomes of KTx.

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“…High circulating levels of IL-6 have been considered a marker of inflammatory response severity after IR [24,25]. Cicora et al [26] showed that even in autotransplantation there is a significant increase in serum levels of creatinine and urea 24 h after IR. The group also observed an increased expression of IL-6 (immunohistochemistry) in the renal tissue.…”

Section: Discussionmentioning

confidence: 99%

TLR2 and TLR4 expression after kidney ischemia and reperfusion injury in mice treated with FTY720

Pedregosa

Haidar

Hirata

et al. 2011

International Immunopharmacology

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Ischemia and reperfusion injury (IR) is an antigen independent inflammatory process that causes tissue damage. After IR, kidneys up-regulate leukocyte adhesion molecules and toll-like receptors (TLRs). Moreover, injured kidneys can also secrete factors (i.e. heat shock protein) which bind to TLRs and trigger intracellular events culminating with the increase in the gene expression of inflammatory cytokines. FTY720 is an immunomodulatory compound and protects at least in part kidneys submitted to IR. The mechanisms associated with FTY720's beneficial effects on kidneys after IR remain elusive. We investigated whether FTY720 administration in mice submitted to kidney IR is associated with modulation of TLR2 and TLR4 expression. C57BL/6 mice submitted to 30min of renal pedicles clamp were evaluated for serum parameters (creatinine, urea and nitric oxide), kidney histology, spleen and kidney infiltrating cells expression of TLR2 and TLR4, resident kidney cells expression of TLR2 and TLR4 and IL-6 protein expression in kidney. FTY720-treated mice presented decrease in serum creatinine, urea and nitric oxide, diminished expression of TLR2 and TLR4 both in spleen and kidney infiltrating cells, and reduced kidney IL-6 protein expression in comparison with IR non-treated mice. However, acute tubular necrosis was present both in IR non-treated and IR+FTY720-treated groups. Also, FTY720 did not prevent TLR2 and TLR4 expression in kidney resident cells. In conclusion, FTY720 can promote kidney function recovery after IR by reducing the inflammatory process. Further studies are needed in order to establish whether TLR2 and TLR4 down regulation should be therapeutically addressed as protective targets of renal function and structure after IR.

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Protective effect of immunosuppressive treatment before orthotopic kidney autotransplantation

Cited by 11 publications

References 46 publications

Autophagy and the Kidney: Implications for Ischemia-Reperfusion Injury and Therapy

Autophagy and the Kidney: Implications for Ischemia-Reperfusion Injury and Therapy

Carbon monoxide inhibits apoptosis during cold storage and protects kidney grafts donated after cardiac death

TLR2 and TLR4 expression after kidney ischemia and reperfusion injury in mice treated with FTY720

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