Experimental kidney transplantation in pigs from non–heart-beating donors: evaluation of renal artery flow

Alcoberro, J; Alcaraz, Antonio; Álvarez-Vijande, R.; Calatrava, P; Luqué, Pilar; Rodríguez, A.; Aguilar, Andrea; Gibanel, R; Llopis, Jaume; Solé, Manel; Farré, Xavier; Helena, Maria; Talbot-Wright, R

doi:10.1016/s0041-1345(99)00373-5

Cited by 10 publications

(5 citation statements)

References 5 publications

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“…Ischemic reperfusion injury (IRI) is the main risk for kidney transplantation and long‐term graft function. One of the primary mechanisms affecting renal IRI is microvascular dysfunction, which results in secondary tissue hypoxia and mitochondrial failure . Our previous work has already found that HMP can improve kidney function (more urine output and lower serum creatinine/BUN) after 24 h of reperfusion in the same rabbit model compared to CS .…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of Hypothermic Machine Perfusion to Decrease Donation After Cardiac Death Graft Inflammation: Through the Pathway of Upregulating Expression of KLF2 and Inhibiting TGF-β Signaling

et al. 2016

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Hypothermic machine perfusion (HMP) has been known as an efficient way to improve kidney graft function, but the underlying mechanisms remain unclear. Here, we adopt a rabbit reperfusion mode to investigate the upstream mechanisms of end-ischemic HMP of kidneys from donors after cardiac death (DCD), with static cold storage (CS) as a control. Eighteen New Zealand healthy male rabbits (12 weeks old, with a weight of 3.0 ± 0.2 kg) were randomly divided into three groups: HMP group, CS group, and Normal group (n = 6). The left kidney of rabbits underwent warm ischemia for 25 min through clamping the left renal pedicle and then reperfusion for 1 h. Then the left kidneys were preserved by CS or HMP (4°C for 4 h) ex vivo respectively, after they were autotransplanted and rabbits were submitted to a right nephrectomy. Twenty-four hours after reperfusion, all left renal specimens were collected. Finally, the expression of Krüppel-like factor 2 (KLF2), transforming growth factor-β (TGF-β) and SMAD4 protein in renal cortical tissue were detected by immunoblotting, and the TGF-β and SMAD4 expressions were further confirmed by immunohistochemistry analysis. We found that expression of KLF2 in HMP group was significantly higher than CS group (P = 0.011), while expression of TGF-β and SMAD4 in HMP group were significantly lower than CS group (P = 0.002, P = 0.01, respectively); Compared with normal group, the expression of TGF-β and SMAD4 in HMP and CS group significantly increased (P<0.05). Compared with CS group, TGF-β and SMAD4 protein were equally down-regulated in glomerular and the tubular epithelial cells in HMP group confirmed by immunohistochemistry. In conclusion, HMP may decrease DCD kidneys inflammation through the pathway of upregulating expression of KLF2 and inhibiting TGF-β signaling after transplantation.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of Hypothermic Machine Perfusion to Decrease Donation After Cardiac Death Graft Inflammation: Through the Pathway of Upregulating Expression of KLF2 and Inhibiting TGF-β Signaling

et al. 2016

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“…One primary mechanism contributing to renal ischemic reperfusion injury is described to be microvascular dysfunction, resulting in secondary tissue hypoxia and mitochondrial failure .…”

Section: Discussionmentioning

confidence: 99%

One or 4 h of “in-house” reconditioning by machine perfusion after cold storage improve reperfusion parameters in porcine kidneys

et al. 2014

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SummaryIn-house machine perfusion after cold storage (hypothermic reconditioning) has been proposed as convenient tool to improve kidney graft function. This study investigated the role of machine perfusion duration for early reperfusion parameters in porcine kidneys. Kidney function after cold preservation (4°C, 18 h) and subsequent reconditioning by one or 4 h of pulsatile, nonoxygenated hypothermic machine perfusion (HMP) was studied in an isolated kidney perfusion model in pigs (n = 6, respectively) and compared with simply cold-stored grafts (CS). Compared with CS alone, one or 4 h of subsequent HMP similarly and significantly improved renal flow and kidney function (clearance and sodium reabsorption) upon warm reperfusion, along with reduced perfusate concentrations of endothelin-1 and increased vascular release of nitric oxide. Molecular effects of HMP comprised a significant (vs CS) mRNA increase in the endothelial transcription factor KLF2 and lower expression of endothelin that were observed already at the end of one-hour HMP after CS. Reconditioning of coldstored kidneys is possible, even if clinical logistics only permit one hour of therapy, while limited extension of the overall storage time by in-house machine perfusion might also allow for postponing of transplantation from night to early day work.

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“…The main application field was ischemic injury, but there are also some reported experiences in the field of transplantation. In fact, pretransplant graft perfusion or administration of iloprost in the early days post-transplant led to some benefits in cases of DGF and of cyclosporin-induced toxicity (18,35,(37)(38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Iloprost in Acute Post-kidney Transplant Atheroembolism: A Case Report of Two Successful Treatments

et al. 2020

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Cholesterol embolization (CE) is a rare and alarming post-transplant complication, responsible for primary non-function (PNF) or delayed graft function (DGF). Its incidence is expected to rise due to increasingly old donors and recipients and the extended criteria for donation. Therapy with statins and steroids has not been shown to be effective, while agonism of prostaglandin I 2 has been reported to be useful in systemic CE. We report two cases of acute post-transplant CE in which intravenous iloprost (0.05 mg/kg/day) was added to standard statin and steroid therapy. In the first instance, CE was due to embolization from the kidney artery resulting in embolization of the small vessels; after a long DGF and 15 days of iloprost therapy, renal function recovered. The second instance is a case of embolization from the iliac artery of the recipient, where CE manifested as a partial renal infarction. After 5 days of iloprost administration, creatinine levels improved. Iloprost acts on vasodilation and on different inflammatory pathways, improving the anti-inflammatory profile. Post-transplant CE is difficult to diagnose and, if not treated, can lead to loss of function. Iloprost added to standard therapy could be beneficial in accelerating renal function recovery immediately after transplant.

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Experimental kidney transplantation in pigs from non–heart-beating donors: evaluation of renal artery flow

Cited by 10 publications

References 5 publications

Mechanisms of Hypothermic Machine Perfusion to Decrease Donation After Cardiac Death Graft Inflammation: Through the Pathway of Upregulating Expression of KLF2 and Inhibiting TGF-β Signaling

Mechanisms of Hypothermic Machine Perfusion to Decrease Donation After Cardiac Death Graft Inflammation: Through the Pathway of Upregulating Expression of KLF2 and Inhibiting TGF-β Signaling

One or 4 h of “in-house” reconditioning by machine perfusion after cold storage improve reperfusion parameters in porcine kidneys

Iloprost in Acute Post-kidney Transplant Atheroembolism: A Case Report of Two Successful Treatments

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