A Case-Control Comparison of the Results of Renal Transplantation From Heart-Beating and Non-Heart-Beating Donors

Metcalfe, Matthew S.; Butterworth, P.C.; White, Steve; Saunders, R. N.; Murphy, Gavin J.; Taub, Nick; Veitch, P. S.; Nicholson, Michael L.

doi:10.1097/00007890-200106150-00012

Cited by 73 publications

(39 citation statements)

References 14 publications

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“…28,29 Such kidneys may be subjected to longer periods of warm ischemia during retrieval and consequently are more susceptible to IRI during implantation. [30][31][32][33] Developing strategies, including pharmacological interventions to improve the outcomes of these 'extended criteria' allografts is of the upmost importance.…”

Section: Discussionmentioning

confidence: 99%

A novel rodent model of severe renal ischemia reperfusion injury

et al. 2016

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Renal ischemia reperfusion injury (IRI) is a major problem, currently without treatments in clinical use. This reflects the failure of animal models to mimic the severity of IRI observed in clinical practice. Most described models lack both the ability to inflict a permanent reduction in renal function and the sensitivity to demonstrate the protective efficacy of different therapies in vivo. To test novel cell-based therapies, we have developed a model of renal IRI in Fisher 344 rats. Animals were subjected to 120 min of unilateral warm ischemia, during which they underwent an intra-renal artery infusion of therapeutic agents or vehicle. At either 2 or 6 weeks post-surgery, animals underwent terminal glomerular filtration rate (GFR) studies by inulin clearance to most accurately quantify renal function. Harvested kidneys underwent histological analysis. Compared to sham operations, saline treated animals suffered a long-term reduction in GFR of &50%. Histology revealed short-and long-term disruption of renal architecture. Despite the injury severity, postoperative animal losses are 55%. This model produces a severe, consistent renal injury that closely replicates the pathological processes encountered in clinical medicine. Renal artery infusion mimics the route likely employed in clinical transplantation, where the renal artery is accessible. Inulin clearance characterizes GFR, allowing full assessment of therapeutic intervention. This model is useful for screening therapeutic agents prior to testing in a transplant model. This reduces animal numbers needed to test drugs for clinical transplantation and allows for refinement of dosing schedules.

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Section: Discussionmentioning

confidence: 99%

A novel rodent model of severe renal ischemia reperfusion injury

et al. 2016

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“…The process of IRI is accelerated in recipients receiving organs from ECDs and DCDs. This reflects in increased rates of delayed graft function and primary non-function as a consequence of the associated ischaemia especially the prolonged warm ischaemic insult sustained during organ retrieval and added cold storage time [4,9,10]. In the native kidney situation, AKI affects 7–10% of all hospitalised patients and can be associated with a mortality rate of 35–40% for inpatients and 75% for patients with sepsis-associated renal failure [11].…”

Section: Introductionmentioning

confidence: 99%

Stem Cells and Their Role in Renal Ischaemia Reperfusion Injury

Bagul

Frost

Drage³

2012

Am J Nephrol

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Background: Ischaemia-reperfusion injury (IRI) remains one of the leading causes of acute kidney injury (AKI). IRI is an underlying multifactorial pathophysiological process which affects the outcome in both native and transplanted patients. The high morbidity and mortality associated with IRI/AKI and disappointing results from current available clinical therapeutic approaches prompt further research. Stem cells (SC) are undifferentiated cells that can undergo both renewal and differentiation into one or more cell types which can possibly ameliorate IRI. Aim: To carry out a detailed literature analysis and construct a comprehensive literature review addressing the role of SC in AKI secondary to IRI. Methods: Evidence favouring the role of SC in renal IRI and evidence showing no benefits of SC in renal IRI are the two main aspects to be studied. The search strategy was based on an extensive search addressing MESH terms and free text terms. Results: The majority of studies in the field of renal IRI and stem cell therapy show substantial benefits. Conclusions: Studies were mostly conducted in small animal models, thus underscoring the need for further pre-clinical studies in larger animal models, and results should be taken with caution. SC therapy may be promising though controversy exists in the exact mechanism. Thorough scientific exploration is required to assess mechanism, safety profile, reproducibility and methods to monitor administered SC.

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“…Compared with living and brain dead donor organs, kidneys from NHB donors are subjected to significantly more ischemia-reperfusion (I/R) injury, and this is reflected in higher rates of both primary non-function (PNF) and delayed graft function (DGF) [1][2][3]. This has stimulated developments in the preservation of marginal organs and, in particular, the use of modern technology to improve organ preservation techniques.…”

Section: Introductionmentioning

confidence: 99%