Ignite Creation Date:
2024-05-06 @ 8:24 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06374121
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-18
First Post:
2024-04-10
Brief Title:
Kidney Perfusion With or Without Absorption
Sponsor:
Mario Negri Institute for Pharmacological Research
Organization:
Mario Negri Institute for Pharmacological Research
Study Overview
Official Title:
A Single-center Pilot Prospective Randomized Clinical Study of Hypothermic Oxygenated Perfusion With or Without Adsorption in Histologically Evaluated Kidneys Retrieved From Marginal Donors
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
POWER
Brief Summary:
In this single-center pilot prospective randomized study the investigators will compare the biochemical profiles of the perfusate and the functional parameters of five kidneys perfused with Integrated PerLife system and PerSorb ECOS-300CY sorbent adsorption groups with the profiles of the perfusate and functional parameters of five matched kidneys perfused with Integrated PerLife system only non-adsorption group Kidneys from marginal donors with a clinical indication to pre-transplant histological evaluation donor 70-years-old or aged 60 to 69 years but with hypertension diabetes andor clinical proteinuria will be allocated to perfusion with or without adsorption using a 11 randomization ratio When both donor kidneys will have a score from 0 to 4 the two kidneys will be used for two single transplants When one kidney will have a score from 0 to 4 and the other kidney will have a score of 5 or more and when both kidneys will have a score from 5 to 7 the two kidneys will be transplanted together into the same recipient If one kidney will have a score from 5 to 7 and the other kidney will have a score of 8 or greater the two kidneys will be discarded With the use of the minimization method the randomization will be planned in order to have the same number of single or dual transplants in the perfusion kidney groups with or without adsorption Donor selection kidney evaluation and allocation and recipient management will be based on per center practice
Detailed Description:
In recent years growing interest has been addressed to the use of dynamic preservation of the kidneys as a tool to improve graft function and survival Retrospective analyses and a randomized controlled trial showed that pre-transplant machine perfusion MP is associated with a lower incidence of delayed graft function DGF and improved one-year graft survival as compared with static cold storage However the overall beneficial effect of MP on transplant outcomes is largely driven by treatment effect in recipients of grafts from marginal donors
Hypothermic oxygenated perfusion has been found to reduce early allograft injury and to improve post-transplant outcomes in a randomized controlled trial of liver transplantation from older donors In vitro studies show that perfusion reduces endothelial damage to the sinusoidal capillaries and increases adenosine triphosphate production As far as kidney transplantation is concerned little data is available on the outcomes of grafts treated with perfusion In rat models of allogeneic kidney transplant perfusion-treated grafts displayed better short-term function less tubular injury fewer interstitial infiltrates of immune cells and milder endothelial activation than the untreated counterparts
MP is not only beneficial per se It can also be exploited as a means to deliver additional treatment to the graft For instance there is in vivo evidence that hemoadsorption improves renal blood flow during perfusion and reduces the release of cytokines and prostaglandins at reperfusion in a porcine model of kidney transplantation Beneficial effects of hemoadsorption have been documented in the setting of continuous renal replacement treatment for septic shock In the setting of pre-transplant organ conditioning cytokine adsorption paired to normothermic perfusion has been found to reduce inflammatory gene expression and increase oxidative phosphorylation pathway gene expression in human kidneys Whether adsorption paired to perfusion reduces the inflammatory response and whether this is of clinical relevance in transplantation of histologically evaluated kidneys from marginal donors is worth investigating
Hypothermic oxygenated perfusion has been found to reduce early allograft injury and to improve post-transplant outcomes in a randomized controlled trial of liver transplantation from older donors In vitro studies show that perfusion reduces endothelial damage to the sinusoidal capillaries and increases adenosine triphosphate production As far as kidney transplantation is concerned little data is available on the outcomes of grafts treated with perfusion In rat models of allogeneic kidney transplant perfusion-treated grafts displayed better short-term function less tubular injury fewer interstitial infiltrates of immune cells and milder endothelial activation than the untreated counterparts
MP is not only beneficial per se It can also be exploited as a means to deliver additional treatment to the graft For instance there is in vivo evidence that hemoadsorption improves renal blood flow during perfusion and reduces the release of cytokines and prostaglandins at reperfusion in a porcine model of kidney transplantation Beneficial effects of hemoadsorption have been documented in the setting of continuous renal replacement treatment for septic shock In the setting of pre-transplant organ conditioning cytokine adsorption paired to normothermic perfusion has been found to reduce inflammatory gene expression and increase oxidative phosphorylation pathway gene expression in human kidneys Whether adsorption paired to perfusion reduces the inflammatory response and whether this is of clinical relevance in transplantation of histologically evaluated kidneys from marginal donors is worth investigating
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None