PMID- 36582671
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230103
IS  - 2373-8731 (Print)
IS  - 2373-8731 (Electronic)
IS  - 2373-8731 (Linking)
VI  - 9
IP  - 1
DP  - 2023 Jan
TI  - Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before 
      Transplantation: Results From the First-in-human Randomized Phase I Trial.
PG  - e1403
LID - 10.1097/TXD.0000000000001403 [doi]
LID - e1403
AB  - Pretreating porcine kidneys with Corline Heparin Conjugate (CHC) during 
      hypothermic machine perfusion (HMP) has been shown to reduce preservation injury 
      and improve early kidney function. In this first-in-human phase I study, the 
      safety and tolerability of transplanting CHC-pretreated kidneys were evaluated. 
      METHODS: CHC or placebo was added to the preservation solution during HMP of 
      donated kidneys from deceased donors for at least 3 h before transplantation into 
      adult patients. The primary safety endpoint was the number and severity of 
      adverse events (AEs) and serious AEs (SAEs) during the first 30 d after 
      transplantation. RESULTS: In the first 30 d, 66 AEs were reported in 8 patients 
      who received CHC-pretreated kidneys with 39 AEs in 8 patients who received 
      placebo-pretreated kidneys (P = 0.1 in post hoc analysis). The most common AEs 
      were hypertension (CHC, n = 5; placebo, n = 2) and anemia (CHC, n = 5; placebo, 
      n = 2). Most AEs were assessed as mild (58%) or moderate (39%) and not related to 
      treatment (95%). There were 2 SAEs reported in each group. One SAE, considered 
      possibly related to CHC treatment, was a case of severe postprocedural hemorrhage 
      that required reoperation. No patients needed dialysis. There were no observed 
      rejections and no patient deaths. CONCLUSIONS: Pretreatment of kidneys with CHC 
      before transplantation was considered safe and tolerable. Efficacy studies are 
      now planned to investigate if CHC can reduce early ischemia-reperfusion injury in 
      humans.
CI  - Copyright (c) 2022 The Author(s). Transplantation Direct. Published by Wolters 
      Kluwer Health, Inc.
FAU - Sedigh, Amir
AU  - Sedigh A
AD  - Section of Transplantation Surgery, Department of Surgical Sciences, Uppsala 
      University, Uppsala, Sweden.
FAU - Lundgren, Torbjorn
AU  - Lundgren T
AD  - Division of Transplantation Surgery, Department of Clinical Science, Intervention 
      and Technology, Karolinska Institute, Stockholm, Sweden.
FAU - Lindner, Per
AU  - Lindner P
AD  - The Transplant Institute, Institute of Clinical Sciences, Sahlgrenska University 
      Hospital, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
FAU - Nordstrom, Johan
AU  - Nordstrom J
AD  - Division of Transplantation Surgery, Department of Clinical Science, Intervention 
      and Technology, Karolinska Institute, Stockholm, Sweden.
FAU - Magnusson, Peetra
AU  - Magnusson P
AD  - Section of Clinical Immunology, Department of Immunology, Genetics and Pathology, 
      Uppsala University, Uppsala, Sweden.
FAU - Jonsson, Janniz
AU  - Jonsson J
AD  - Section of Transplantation Surgery, Department of Surgical Sciences, Uppsala 
      University, Uppsala, Sweden.
AD  - Section of Clinical Immunology, Department of Immunology, Genetics and Pathology, 
      Uppsala University, Uppsala, Sweden.
FAU - Carlsson, Fredrik
AU  - Carlsson F
AD  - Section of Clinical Immunology, Department of Immunology, Genetics and Pathology, 
      Uppsala University, Uppsala, Sweden.
AD  - Corline Biomedical AB, Uppsala, Sweden.
FAU - Ploeg, Rutger
AU  - Ploeg R
AD  - Nuffield Department of Surgical Sciences, Oxford Transplant Centre, University of 
      Oxford, Oxford, United Kingdom.
FAU - Lorant, Tomas
AU  - Lorant T
AD  - Section of Transplantation Surgery, Department of Surgical Sciences, Uppsala 
      University, Uppsala, Sweden.
LA  - eng
PT  - Journal Article
DEP - 20221222
PL  - United States
TA  - Transplant Direct
JT  - Transplantation direct
JID - 101651609
PMC - PMC9788974
COIS- The study was sponsored by Corline Biomedical AB, who received funding from the 
      EU Commission's Horizon 2020 project (grant 756195). In addition to his 
      affiliation with the Department of Immunology, Genetics, and Pathology, Section 
      of Clinical Immunology, Uppsala University, Uppsala, Sweden, F.C. is also 
      employed by Corline Biomedical AB. R.P. is a scientific advisor for Corline 
      Biomedical AB. The remaining authors have no conflicts of interest to declare.
EDAT- 2022/12/31 06:00
MHDA- 2022/12/31 06:01
PMCR- 2022/12/22
CRDT- 2022/12/30 02:28
PHST- 2022/07/20 00:00 [received]
PHST- 2022/09/02 00:00 [revised]
PHST- 2022/09/18 00:00 [accepted]
PHST- 2022/12/30 02:28 [entrez]
PHST- 2022/12/31 06:00 [pubmed]
PHST- 2022/12/31 06:01 [medline]
PHST- 2022/12/22 00:00 [pmc-release]
AID - 10.1097/TXD.0000000000001403 [doi]
PST - epublish
SO  - Transplant Direct. 2022 Dec 22;9(1):e1403. doi: 10.1097/TXD.0000000000001403. 
      eCollection 2023 Jan.