Kidney Perfusion With or Without Absorption
- Conditions
- Kidney Replacement
- Interventions
- Device: PerSorb cartridge (CytoSorbents Europe GmbH, Germany)Device: PerLife PerKidney
- Registration Number
- NCT06374121
- Lead Sponsor
- Mario Negri Institute for Pharmacological Research
- 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 and/or clinical proteinuria) will be allocated to perfusion with or without adsorption using a 1:1 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
- Males and females older than 50 years eligible for single or dual kidney transplant from marginal donors identified according to the NITp criteria (>70-year-old or 60 to 70 years with hypertension and/or diabetes and/or clinical proteinuria)
- Pre-transplant histological evaluation
- Histological score ≤ 7
- Written informed consent.
- Any factor that represents a contraindication to receive a deceased donor kidney transplant according to the NITp criteria,
- Need for specific desensitization protocols because of a high immunological risk according to the NITp criteria,
- Active enrollment in concomitant intervention studies,
- Macroscopic vascular abnormalities that preclude the possibility of machine perfusion.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Perfusion and concomitant adsorption PerLife PerKidney Kidneys eligible for perfusion will be treated with the PerLife PerKidney system. Kidneys allocated to the adsorption subgroup will receive concomitant treatment with PerSorb cartridge. Perfusion alone PerLife PerKidney Kidneys eligible here will only be treated with the PerLife PerKidney system. Perfusion and concomitant adsorption PerSorb cartridge (CytoSorbents Europe GmbH, Germany) Kidneys eligible for perfusion will be treated with the PerLife PerKidney system. Kidneys allocated to the adsorption subgroup will receive concomitant treatment with PerSorb cartridge.
- Primary Outcome Measures
Name Time Method Perfusate sample collection At clinical perfusion start, after 1 hour, then after 4 hours from start and every 2 hours thereafter, up to perfusion end Pseudo-urine ureteral output will be separately assessed at sequential times during clinical perfusion
Acute kidney injury markers Every 30 minutes during clinical perfusion Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin
Complement activation markers Every 30 minutes during clinical perfusion Complement factor 3a (C3a), complement factor 5a (C5a) and soluble membrane attack complex (sC5bC9)
Oxidative stress markers Every 30 minutes during clinical perfusion Glutathione S-transferase (GST), lactate dehydrogenase (LDH) and free lactate
Vascular resistances Every 30 minutes during clinical perfusion Renal vascular resistances will be automatically collected through clinical perfuzione
Inflammatory cytokine markers Every 30 minutes during clinical perfusion Interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-⍺)
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
ASST - Papa Giovanni XXIII - U.O. Nefrologia e Dialisi/ Mario Negri Institute for Pharmacological Research - Clinical Research Center for Rare Diseases Aldo e Cele Daccò
🇮🇹Bergamo, BG, Italy