A Proof-of-Concept Preclinical Study Using a Novel Thermal Insulation Device in a Porcine Kidney Auto-Transplantation Model

Ernst, Lisa; Czigány, Zoltán; Paschenda, Pascal; Schulz, M; Breuer, Lukas; Kunczik, Janosch; Czaplik, Michael; Liu, Wenjia; Jiang, Decan; Klinge, U.; Djudjaj, Sonja; Lurje, Georg; Kobayashi, Eiji; Tolba, René

doi:10.3390/ijms232213806

Cited by 5 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies using TBB in a porcine kidney model showed that the core temperature of the kidney was lower than the surface temperature, suggesting that renal metabolic activity is suppressed by a sufficiently low surface temperature. 26 Here, we confirmed that TBB can maintain transplanted kidneys at a low temperature during vascular anastomosis and preserve the thermal threshold at the end of anastomosis.…”

Section: Discussionsupporting

confidence: 77%

“…In addition, a recent report on a porcine kidney model demonstrated that TBB reduced tubular damage, indicated by decreased syndecan-1 expression compared with controls. 26 As the measurement of core temperature is not feasible in clinical studies, kidney temperatures were measured using a noncontact infrared thermometer. Previous studies using TBB in a porcine kidney model showed that the core temperature of the kidney was lower than the surface temperature, suggesting that renal metabolic activity is suppressed by a sufficiently low surface temperature.…”

Section: Discussionmentioning

confidence: 99%

“…The TBB potentially provided superior insulation compared with controls. 21 , 26 Besides its high thermal barrier effect, the TBB may also have physical benefits. The elasticity of the TBB, which adheres closely to the kidney, may be effective in preventing kidney tissue edema caused by warm ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Protection From Second Warm Ischemic Injury Using a Thermal Barrier Bag in Kidney Transplantation

Ide

Nakano

Imaoka

et al. 2023

Transplantation Direct

Self Cite

View full text Add to dashboard Cite

K idney transplantation (KT) is the gold-standard treatment for end-stage kidney disease. It provides a superior quality of life and reduces morbidity and mortality compared with dialysis; 1-3 however, limited availability of donor grafts is a major drawback. 4 To address the organ shortage, KTs from brain-dead extended criteria donors (ECDs) 5 and donation after circulatory death (DCD) donors 6 are currently accepted. 7 The quality of organs procured from deceased donors is an important factor determining graft survival and function in KT. Although the most deleterious factor is donor age, second warm ischemic injury during vascular anastomosis adversely affects both immediate posttransplant function and longterm patient and graft survival after KT. 8,9 Possible molecular mechanisms include the generation of reactive oxygen species, induction of apoptosis, and stimulation of innate and adaptive immune systems. 10,11 To reduce the incidence of second warm ischemic injury, efforts should be directed at reducing procedural time for vascular anastomosis or keeping the organ cooler during this period. However, it has been pointed out that the former may result in technical complications and does not seem feasible. 12 Although little is known about the actual values of temperature variations of the kidney during the first or second warm ischemic period, experimental studies indicate that renal metabolic activity resumes at 15 °C to 18 °C13-15 after cold storage. Various techniques for preventing organ Kidney TransplantationBackground. Second warm ischemic injury during vascular anastomosis not only adversely affects immediate posttransplant function but also affects long-term patient and graft survival. We developed a pouch-type thermal barrier bag (TBB) composed of a transparent, biocompatible insulation material suitably designed for kidneys and conducted the first-inhuman clinical trial. Methods. A living-donor nephrectomy was performed using a minimum skin incision procedure. After back table preparation, the kidney graft was placed inside the TBB and preserved during vascular anastomosis. The graft surface temperature was measured before and after vascular anastomosis using a noncontact infrared thermometer. After completion of the anastomosis, the TBB was removed from the transplanted kidney before graft reperfusion. Clinical data, including patient characteristics and perioperative variables, were collected. The primary endpoint was safety, which was assessed by evaluating adverse events. The secondary endpoints were the feasibility, tolerability, and efficacy of the TBB in kidney transplant recipients. Results. Ten living-donor kidney transplant recipients with a median age of 56 y (range, 39-69 y) were enrolled in this study. No serious adverse events related to the TBB were observed. The median second warm ischemic time was 31 (27-39) min, and the median graft surface temperature at the end of anastomosis was 16.1 °C (12.8-18.7 °C). Conclusions. TBB can maintain transplanted kidneys at a low temperature duri...

show abstract

Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Protection From Second Warm Ischemic Injury Using a Thermal Barrier Bag in Kidney Transplantation

Ide

Nakano

Imaoka

et al. 2023

Transplantation Direct

Self Cite

View full text Add to dashboard Cite

show abstract

“…Preclinical studies using pig kidneys are important for demonstrating the efficacy of devices in humans, as these effects cannot be investigated in small animals. 15 Our research using pig kidneys investigates whether creating a hypobaric environment by placing the grafts in a sealed container during the initial perfusion can promote microthrombus removal and reduce graft damage during preservation and reperfusion.…”

mentioning

confidence: 99%

A Novel Hypobaric Perfusion Method to Remove Microthrombi in Kidney Grafts with Prolonged Circulatory Arrest: A Pilot Study on a Porcine Model

Kinoshita,

Iwai,

Torai

et al. 2024

Transplantation Direct

Self Cite

View full text Add to dashboard Cite

Background. Intragraft microthrombi prevent complete organ perfusion, thereby compromising the viability maintained by preservation solutions or machine perfusion. Herein, we developed and evaluated a hypobaric perfusion method for flushing microthrombi from kidney grafts with prolonged circulatory arrest in a porcine model. Methods. Porcine renal grafts with 1-h warm ischemia were flushed with heparin-containing perfusate in a normobaric environment (control group) or a hypobaric environment of −20 to −30 mm Hg (hypobaric perfusion group) for 10 min using a gravity drip from a 1-m height. Perfusion parameters, histological findings in ex vivo blood perfusion experiments (2 control and 4 hypobaric perfusion kidneys), and safety in allogeneic porcine transplantation experiments (1 donor to 2 recipients) were evaluated. Results. The −20 mm Hg hypobaric perfusion group exhibited greater maximal flow than the control group (20.4 versus 6.9 mL/min; P = 0.028). Histological evaluation following 3 h of static cold storage and 10 min ex vivo porcine whole-blood perfusion revealed statistically significant reductions in congestion and edema (1.5 versus 3, and 0.5 versus 4 on a 5-point scale, from 0 to 4; P = 0.014 and 0.006, respectively) in the medulla along with improved ischemia–reperfusion injury scores (4.0 versus 4.7 on a 6-point scale, from 0 to 5; P = 0.004) in the −20 mm Hg hypobaric perfusion group. Kidney grafts perfused under −30 mm Hg hypobaric environment followed by 3 h of static cold storage could be used for porcine allogeneic transplantation without any macroscopic damage to the graft, effect on intraoperative handling, or perioperative adverse events. Thus, the hypobaric perfusion method was considered safe. Conclusions. Perfusion in a hypobaric environment may prevent graft congestion, edema, and further reperfusion injury by flushing out erythrocytes occluding the medullary capillaries, improving marginal renal graft quality, and reducing the number of discarded grafts.

show abstract

“…Their results show that, indeed, the two therapeutic strategies provide additive benefits to liver quality. Finally, Ernst et al [ 16 ] directed their efforts not towards preservation but instead towards alleviating the intermediate period between the end of preservation and anastomosis. Indeed, while the donor organ arteries and veins are anastomosed to the recipient circulation, the organ is subjected to the stress of warm ischemia, known to enhance IRI.…”

mentioning

confidence: 99%

Molecular Frontiers in Transplantation-Induced Ischemia–Reperfusion Injury

Thuillier

2023

IJMS

View full text Add to dashboard Cite

show abstract

A Proof-of-Concept Preclinical Study Using a Novel Thermal Insulation Device in a Porcine Kidney Auto-Transplantation Model

Cited by 5 publications

References 30 publications

Protection From Second Warm Ischemic Injury Using a Thermal Barrier Bag in Kidney Transplantation

Protection From Second Warm Ischemic Injury Using a Thermal Barrier Bag in Kidney Transplantation

A Novel Hypobaric Perfusion Method to Remove Microthrombi in Kidney Grafts with Prolonged Circulatory Arrest: A Pilot Study on a Porcine Model

Molecular Frontiers in Transplantation-Induced Ischemia–Reperfusion Injury

Contact Info

Product

Resources

About