Kidney Perfusion With or Without Absorption

NCT06374121 | Recruiting

• 1 other identifier: POWER
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Replacement

Keywords

Kidney perfusion; Absorption; Marginal donors

Outcome Measures

Primary Outcomes (6)

• Oxidative stress markers

  Glutathione S-transferase (GST), lactate dehydrogenase (LDH) and free lactate

  Every 30 minutes during clinical perfusion

• Acute kidney injury markers

  Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1) and endothelin

  Every 30 minutes during clinical perfusion

• Inflammatory cytokine markers

  Interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-⍺)

  Every 30 minutes during clinical perfusion

• Complement activation markers

  Complement factor 3a (C3a), complement factor 5a (C5a) and soluble membrane attack complex (sC5bC9)

  Every 30 minutes during clinical perfusion

• Vascular resistances

  Renal vascular resistances will be automatically collected through clinical perfuzione

  Every 30 minutes during clinical perfusion

• Perfusate sample collection

  Pseudo-urine ureteral output will be separately assessed at sequential times during clinical perfusion

  At clinical perfusion start, after 1 hour, then after 4 hours from start and every 2 hours thereafter, up to perfusion end

Study Arms (2)

Perfusion and concomitant adsorption

EXPERIMENTAL

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.

Device: PerSorb cartridge (CytoSorbents Europe GmbH, Germany); Device: PerLife PerKidney

Perfusion alone

ACTIVE COMPARATOR

Kidneys eligible here will only be treated with the PerLife PerKidney system.

Device: PerLife PerKidney

Interventions

PerSorb cartridge (CytoSorbents Europe GmbH, Germany) DEVICE

This is a highly bio-/hemo-compatible, low-flow resistance polymer cartridge able to remove cytokines and other inflammatory mediators via adsorption.

Perfusion and concomitant adsorption

PerLife PerKidney DEVICE

The system for ex vivo kidney reconditioning (Aferetica, Italy), which allows hypothermic oxygenated pulsatile perfusion of the organ.

Perfusion alone; Perfusion and concomitant adsorption

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (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, 24027, Italy

RECRUITING

Related Publications (5)

• Remuzzi G, Grinyo J, Ruggenenti P, Beatini M, Cole EH, Milford EL, Brenner BM. Early experience with dual kidney transplantation in adults using expanded donor criteria. Double Kidney Transplant Group (DKG). J Am Soc Nephrol. 1999 Dec;10(12):2591-8. doi: 10.1681/ASN.V10122591.

  PMID: 10589699 BACKGROUND

• Hosgood SA, Moore T, Kleverlaan T, Adams T, Nicholson ML. Haemoadsorption reduces the inflammatory response and improves blood flow during ex vivo renal perfusion in an experimental model. J Transl Med. 2017 Oct 25;15(1):216. doi: 10.1186/s12967-017-1314-5.

  PMID: 29070045 BACKGROUND

• Brouwer WP, Duran S, Kuijper M, Ince C. Hemoadsorption with CytoSorb shows a decreased observed versus expected 28-day all-cause mortality in ICU patients with septic shock: a propensity-score-weighted retrospective study. Crit Care. 2019 Sep 18;23(1):317. doi: 10.1186/s13054-019-2588-1.

  PMID: 31533846 BACKGROUND

• Hosgood SA, Hoff M, Nicholson ML. Treatment of transplant kidneys during machine perfusion. Transpl Int. 2021 Feb;34(2):224-232. doi: 10.1111/tri.13751. Epub 2020 Oct 19.

  PMID: 32970886 BACKGROUND

• Ferdinand JR, Hosgood SA, Moore T, Ferro A, Ward CJ, Castro-Dopico T, Nicholson ML, Clatworthy MR. Cytokine absorption during human kidney perfusion reduces delayed graft function-associated inflammatory gene signature. Am J Transplant. 2021 Jun;21(6):2188-2199. doi: 10.1111/ajt.16371. Epub 2020 Nov 22.

  PMID: 33098231 BACKGROUND

Study Officials

• Giuseppe Remuzzi, MD

  Istituto Di Ricerche Farmacologiche Mario Negri

  STUDY CHAIR

Central Study Contacts

Camillo Carrara, MD

CONTACT

+3903545351; pruggenenti@asst-pg23.it

Piero L Ruggenenti, MD

CONTACT

pruggenenti@asst-pg23.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: To compare the biochemical profiles of the perfusate obtained from 5 kidneys treated with perfusion and concomitant adsorption, with that of the perfusate obtained from 5 kidneys treated with perfusion without adsorption.

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: April 18, 2024
• Study Start: October 22, 2024
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: November 22, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)