Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial

Amir Sedigh; Torbjörn Lundgren; Per Lindnér; Johan Nordström; Peetra Magnusson; Janniz Jönsson; Fredrik Carlsson; Rutger Ploeg; Tomas Lorant

doi:10.1097/TXD.0000000000001403

Heparin Conjugate Pretreatment of Kidneys From Deceased Donors Before Transplantation: Results From the First-in-human Randomized Phase I Trial

Transplant Direct. 2022 Dec 22;9(1):e1403. doi: 10.1097/TXD.0000000000001403. eCollection 2023 Jan.

Authors

Amir Sedigh¹, Torbjörn Lundgren², Per Lindnér³, Johan Nordström², Peetra Magnusson⁴, Janniz Jönsson^{1

4}, Fredrik Carlsson^{4

5}, Rutger Ploeg⁶, Tomas Lorant¹

Affiliations

¹ 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.
⁴ Section of Clinical Immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
⁵ Corline Biomedical AB, Uppsala, Sweden.
⁶ Nuffield Department of Surgical Sciences, Oxford Transplant Centre, University of Oxford, Oxford, United Kingdom.

Abstract

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.