Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis—a proteomics study

Weißenbacher, Annemarie; Huang, Honglei; Surik, Tomas; Faro, Maria Letizia Lo; Ploeg, Rutger J.; Coussios, Constantin; Friend, Peter J.; Kessler, Benedikt M.

doi:10.1111/ajt.16334

Cited by 22 publications

(27 citation statements)

References 33 publications

(59 reference statements)

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“…For NMP of the kidney, it is necessary to dilute it with a crystalloid solution to prevent cellular damage and diffuse vacuolation of the tubular cells. Weissenbacher et al 118 , 119 also advocated the use of prolonged periods of NMP and demonstrated that by recirculating the urine the kidney could maintain a more stable environment.…”

Section: Kidney Preservation Techniquesmentioning

confidence: 99%

Advances in Kidney Preservation Techniques and Their Application in Clinical Practice

Hosgood

Brown²,

Nicholson³

2021

Transplantation

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The use of cold preservation solutions to rapidly flush and cool the kidney followed by static cold storage in ice has been the standard kidney preservation technique for the last 50 y. Nonetheless, changing donor demographics that include organs from extended criteria donors and donation after circulatory death donors have led to the adoption of more diverse techniques of preservation. Comparison of hypothermic machine perfusion and static cold storage techniques for deceased donor kidneys has long been debated and is still contested by some. The recent modification of hypothermic machine perfusion techniques with the addition of oxygen or perfusion at subnormothermic or near-normothermic temperatures are promising strategies that are emerging in clinical practice. In addition, the use of normothermic regional perfusion to resuscitate abdominal organs of donation after circulatory death donors in situ before cold flushing is also increasingly being utilized. This review provides a synopsis of the different types of preservation techniques including their mechanistic effects and the outcome of their application in clinical practice for different types of donor kidney.

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Section: Kidney Preservation Techniquesmentioning

confidence: 99%

Advances in Kidney Preservation Techniques and Their Application in Clinical Practice

Hosgood

Brown²,

Nicholson³

2021

Transplantation

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“…They revealed that long-term normothermic preservation significantly reduces tubular injury and improves kidney function, compared to SCS, HMP or end-ischemia short-term NMP (72)(73)(74)(75)(76)(77)(78). The most recent works already demonstrated the safety and feasibility of 24 h kidney NMP, though these grafts were not implanted (79)(80)(81)(82). Importantly, Weissenbacher et al in porcine and nontransplantable human kidneys experiments revealed, that one key factor allowing prolongation of NMP is urine recirculation (80)(81)(82).…”

Section: Normothermic Machine Perfusionmentioning

confidence: 99%

“…The most recent works already demonstrated the safety and feasibility of 24 h kidney NMP, though these grafts were not implanted (79)(80)(81)(82). Importantly, Weissenbacher et al in porcine and nontransplantable human kidneys experiments revealed, that one key factor allowing prolongation of NMP is urine recirculation (80)(81)(82). Perfusate homeostasis and stable kidney arterial flow could be achieved only by urine recirculation (80,82).…”

Section: Normothermic Machine Perfusionmentioning

confidence: 99%

“…Perfusate homeostasis and stable kidney arterial flow could be achieved only by urine recirculation (80,82). Moreover, proteomics analysis showed decreased damage-associated molecular patterns, angiotensinogen levels, and enhanced levels of enzymes involved in kidney metabolism, perfused with urine recirculation (81). Pool et al recently demonstrated that perfusate composition also significantly impact kidney injury and perfusion parameters during prolonged NMP (83).…”

Section: Normothermic Machine Perfusionmentioning

confidence: 99%

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Ex-vivo Kidney Machine Perfusion: Therapeutic Potential

et al. 2021

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Kidney transplantation remains the gold standard treatment for patients suffering from end-stage kidney disease. To meet the constantly growing organ demands grafts donated after circulatory death (DCD) or retrieved from extended criteria donors (ECD) are increasingly utilized. Not surprisingly, usage of those organs is challenging due to their susceptibility to ischemia-reperfusion injury, high immunogenicity, and demanding immune regulation after implantation. Lately, a lot of effort has been put into improvement of kidney preservation strategies. After demonstrating a definite advantage over static cold storage in reduction of delayed graft function rates in randomized-controlled clinical trials, hypothermic machine perfusion has already found its place in clinical practice of kidney transplantation. Nevertheless, an active investigation of perfusion variables, such as temperature (normothermic or subnormothermic), oxygen supply and perfusate composition, is already bringing evidence that ex-vivo machine perfusion has a potential not only to maintain kidney viability, but also serve as a platform for organ conditioning, targeted treatment and even improve its quality. Many different therapies, including pharmacological agents, gene therapy, mesenchymal stromal cells, or nanoparticles (NPs), have been successfully delivered directly to the kidney during ex-vivo machine perfusion in experimental models, making a big step toward achievement of two main goals in transplant surgery: minimization of graft ischemia-reperfusion injury and reduction of immunogenicity (or even reaching tolerance). In this comprehensive review current state of evidence regarding ex-vivo kidney machine perfusion and its capacity in kidney graft treatment is presented. Moreover, challenges in application of these novel techniques in clinical practice are discussed.

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“…Eighteen kidneys from ECD were utilized for NMP prior to transplantation, with a significantly lower rate of DGF in the NMP group, compared to SCS allografts (5.6% vs. 36%) [ 30 ]. Weissenbacher et al demonstrated that urine recirculation during prolonged NMP of discarded kidneys ameliorated metabolic processes and led to enhanced kidney organ function recovery [ 31 ].…”

Section: Bridging Time To Transplantation—from Static Cold Storage To Machine Perfusionmentioning

confidence: 99%

Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs

Bogensperger

Hofmann

Messner

et al. 2021

IJMS

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Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.

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Urine recirculation prolongs normothermic kidney perfusion via more optimal metabolic homeostasis—a proteomics study

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 22 publications

References 33 publications

Advances in Kidney Preservation Techniques and Their Application in Clinical Practice

Advances in Kidney Preservation Techniques and Their Application in Clinical Practice

Ex-vivo Kidney Machine Perfusion: Therapeutic Potential

Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs

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