RECOVERY OF GLOMERULAR AND TUBULAR FUNCTION IN AUTOTRANSPLANTED DOG KIDNEYS PRESERVED BY HYPOTHERMIC STORAGE OR MACHINE PERFUSION

1986 ◽  
Vol 42 (5) ◽  
pp. 453-457 ◽  
Author(s):  
Christine M. Gregg ◽  
Louis R. Cos ◽  
Pradeep Saraf ◽  
Charlotte W. Fridd ◽  
Charles A. Linke
2005 ◽  
Vol 37 (1) ◽  
pp. 329-331 ◽  
Author(s):  
M. Bessems ◽  
B.M. Doorschodt ◽  
O. Hooijschuur ◽  
A.K. van Vliet ◽  
T.M. van Gulik

2021 ◽  
Author(s):  
Sarah Bouari ◽  
Özgür Eryigit ◽  
Ron W. F. Bruin ◽  
Jan N. M. IJzermans ◽  
Robert C. Minnee

Author(s):  
Stefan Wörner ◽  
Bernhard N. Bohnert ◽  
Matthias Wörn ◽  
Mengyun Xiao ◽  
Andrea Janessa ◽  
...  

AbstractTreatment with aprotinin, a broad-spectrum serine protease inhibitor with a molecular weight of 6512 Da, was associated with acute kidney injury, which was one of the reasons for withdrawal from the market in 2007. Inhibition of renal serine proteases regulating the epithelial sodium channel ENaC could be a possible mechanism. Herein, we studied the effect of aprotinin in wild-type 129S1/SvImJ mice on sodium handling, tubular function, and integrity under a control and low-salt diet. Mice were studied in metabolic cages, and aprotinin was delivered by subcutaneously implanted sustained release pellets (2 mg/day over 10 days). Mean urinary aprotinin concentration ranged between 642 ± 135 (day 2) and 127 ± 16 (day 8) µg/mL . Aprotinin caused impaired sodium preservation under a low-salt diet while stimulating excessive hyperaldosteronism and unexpectedly, proteolytic activation of ENaC. Aprotinin inhibited proximal tubular function leading to glucosuria and proteinuria. Plasma urea and cystatin C concentration increased significantly under aprotinin treatment. Kidney tissues from aprotinin-treated mice showed accumulation of intracellular aprotinin and expression of the kidney injury molecule 1 (KIM-1). In electron microscopy, electron-dense deposits were observed. There was no evidence for kidney injury in mice treated with a lower aprotinin dose (0.5 mg/day). In conclusion, high doses of aprotinin exert nephrotoxic effects by accumulation in the tubular system of healthy mice, leading to inhibition of proximal tubular function and counterregulatory stimulation of ENaC-mediated sodium transport.


2021 ◽  
Vol 2 (2) ◽  
pp. 149-161
Author(s):  
Rebecca Panconesi ◽  
Mauricio Flores Carvalho ◽  
Matteo Mueller ◽  
Philipp Dutkowski ◽  
Paolo Muiesan ◽  
...  

Although machine perfusion is a hot topic today, we are just at the beginning of understanding the underlying mechanisms of protection. Recently, the first randomized controlled trial reported a significant reduction of ischemic cholangiopathies after transplantation of livers donated after circulatory death, provided the grafts were treated with an endischemic hypothermic oxygenated perfusion (HOPE). This approach has been known for more than fifty years, and was initially mainly used to preserve kidneys before implantation. Today there is an increasing interest in this and other dynamic preservation technologies and various centers have tested different approaches in clinical trials and cohort studies. Based on this, there is a need for uniform perfusion settings (perfusion route and duration), and the development of general guidelines regarding the duration of cold storage in context of the overall donor risk is also required to better compare various trial results. This article will highlight how cold perfusion protects organs mechanistically, and target such technical challenges with the perfusion setting. Finally, the options for viability testing during hypothermic perfusion will be discussed.


2021 ◽  
Vol 8 (4) ◽  
pp. 39
Author(s):  
Luciana Da Silveira Cavalcante ◽  
Shannon N. Tessier

Heart transplantation became a reality at the end of the 1960s as a life-saving option for patients with end-stage heart failure. Static cold storage (SCS) at 4–6 °C has remained the standard for heart preservation for decades. However, SCS only allows for short-term storage that precludes optimal matching programs, requires emergency surgeries, and results in the unnecessary discard of organs. Among the alternatives seeking to extend ex vivo lifespan and mitigate the shortage of organs are sub-zero or machine perfusion modalities. Sub-zero approaches aim to prolong cold ischemia tolerance by deepening metabolic stasis, while machine perfusion aims to support metabolism through the continuous delivery of oxygen and nutrients. Each of these approaches hold promise; however, complex barriers must be overcome before their potential can be fully realized. We suggest that one barrier facing all experimental efforts to extend ex vivo lifespan are limited research tools. Mammalian models are usually the first choice due to translational aspects, yet experimentation can be restricted by expertise, time, and resources. Instead, there are instances when smaller vertebrate models, like the zebrafish, could fill critical experimental gaps in the field. Taken together, this review provides a summary of the current gold standard for heart preservation as well as new technologies in ex vivo lifespan extension. Furthermore, we describe how existing tools in zebrafish research, including isolated organ, cell specific and functional assays, as well as molecular tools, could complement and elevate heart preservation research.


1977 ◽  
Vol 2 (11) ◽  
pp. 353-356 ◽  
Author(s):  
V. C. Marshall ◽  
H. Ross ◽  
D. F. Scott ◽  
S. McInnes ◽  
N. Thomson ◽  
...  

2021 ◽  
Author(s):  
Jason B. Doppenberg ◽  
Marjolein Leemkuil ◽  
Marten A. Engelse ◽  
Christina Krikke ◽  
Eelco J.P. de Koning ◽  
...  

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