Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial
Background. 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 ki...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer
2023-01-01
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| Series: | Transplantation Direct |
| Online Access: | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001403 |
| _version_ | 1797947151326642176 |
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| author | Amir Sedigh, MD, PhD Torbjörn Lundgren, MD, PhD Per Lindnér, MD, PhD Johan Nordström, MD Peetra Magnusson, MD, PhD Janniz Jönsson, MD Fredrik Carlsson, MD, PhD Rutger Ploeg, MD, PhD Tomas Lorant, MD, PhD |
| author_facet | Amir Sedigh, MD, PhD Torbjörn Lundgren, MD, PhD Per Lindnér, MD, PhD Johan Nordström, MD Peetra Magnusson, MD, PhD Janniz Jönsson, MD Fredrik Carlsson, MD, PhD Rutger Ploeg, MD, PhD Tomas Lorant, MD, PhD |
| author_sort | Amir Sedigh, MD, PhD |
| collection | DOAJ |
| description | Background. 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. |
| first_indexed | 2024-04-10T21:22:17Z |
| format | Article |
| id | doaj.art-e33b970ea67e4a7b8f59b8d0f9696af0 |
| institution | Directory Open Access Journal |
| issn | 2373-8731 |
| language | English |
| last_indexed | 2024-04-10T21:22:17Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer |
| record_format | Article |
| series | Transplantation Direct |
| spelling | doaj.art-e33b970ea67e4a7b8f59b8d0f9696af02023-01-20T02:41:41ZengWolters KluwerTransplantation Direct2373-87312023-01-0191e140310.1097/TXD.0000000000001403202301000-00010Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I TrialAmir Sedigh, MD, PhD0Torbjörn Lundgren, MD, PhD1Per Lindnér, MD, PhD2Johan Nordström, MD3Peetra Magnusson, MD, PhD4Janniz Jönsson, MD5Fredrik Carlsson, MD, PhD6Rutger Ploeg, MD, PhD7Tomas Lorant, MD, PhD81 Section of Transplantation Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.2 Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.3 The Transplant Institute, Institute of Clinical Sciences, Sahlgrenska University Hospital, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.2 Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institute, Stockholm, Sweden.4 Section of Clinical Immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.1 Section of Transplantation Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.4 Section of Clinical Immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.6 Nuffield Department of Surgical Sciences, Oxford Transplant Centre, University of Oxford, Oxford, United Kingdom.1 Section of Transplantation Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.Background. 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.http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001403 |
| spellingShingle | Amir Sedigh, MD, PhD Torbjörn Lundgren, MD, PhD Per Lindnér, MD, PhD Johan Nordström, MD Peetra Magnusson, MD, PhD Janniz Jönsson, MD Fredrik Carlsson, MD, PhD Rutger Ploeg, MD, PhD Tomas Lorant, MD, PhD Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial Transplantation Direct |
| title | Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial |
| title_full | Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial |
| title_fullStr | Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial |
| title_full_unstemmed | Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial |
| title_short | Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial |
| title_sort | heparin conjugate pretreatment of kidneys from deceased donors before transplantation results from the first in human randomized phase i trial |
| url | http://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001403 |
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