TY - JOUR
T1 - Alkaline phosphatase to treat ischaemia-reperfusion injury in living-donor kidney transplantation
T2 - APhIRI I feasibility pilot study
AU - Steenvoorden, Thei S
AU - van Duin, Robert E
AU - Rood, Janneke A J
AU - Peters-Sengers, Hessel
AU - Nurmohamed, Azam S
AU - Bemelman, Frederike J
AU - Vogt, Liffert
AU - van der Heijden, Joost W
N1 - Funding Information: This study was funded by Alloksys Life Sciences B.V. Funding information Publisher Copyright: © 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PY - 2023/12
Y1 - 2023/12
N2 - AIMS: Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of kidney transplantation. This study aimed to evaluate the safety and feasibility of peri-procedural AP administration in living donor kidney transplantation.METHODS: In this double blind, randomized, placebo-controlled, single-center pilot study, all eligible recipients of living donor kidneys were asked to give informed consent. AP (bRESCAP) or a placebo was administered intravenously over 24 hours after the transplantation procedure. The primary outcome-graft function at 1 year-was represented by iohexol measured glomerular filtration rate (mGFR). Serum and urine biomarkers within seven days after surgery were used as surrogate markers of kidney function and injury.RESULTS: Eleven patients were enrolled of whom five were treated with bRESCAP and six with placebo. After 1 year, mGFR was not different between groups. No specific adverse events were observed in the bRESCAP group. Urine expression of injury biomarkers CCL14, NGAL and Cystatin C was lower in the bRESCAP group at day seven. This was statistically significant.CONCLUSION: This study illustrates that bRESCAP treatment is feasible in kidney transplantation, might have a dampening effect on IRI induced renal inflammation, and raises no safety concerns. Future research will evaluate the effects of bRESCAP treatment in donation after circulatory death kidney transplantation where IRI is more pronounced.
AB - AIMS: Ischemia-reperfusion injury (IRI) during kidney transplant procedures is associated with adverse outcome. Alkaline phosphatase (AP) is an enzyme that has the potential to dampen IRI. Prior to this study, it had not been tested in the setting of kidney transplantation. This study aimed to evaluate the safety and feasibility of peri-procedural AP administration in living donor kidney transplantation.METHODS: In this double blind, randomized, placebo-controlled, single-center pilot study, all eligible recipients of living donor kidneys were asked to give informed consent. AP (bRESCAP) or a placebo was administered intravenously over 24 hours after the transplantation procedure. The primary outcome-graft function at 1 year-was represented by iohexol measured glomerular filtration rate (mGFR). Serum and urine biomarkers within seven days after surgery were used as surrogate markers of kidney function and injury.RESULTS: Eleven patients were enrolled of whom five were treated with bRESCAP and six with placebo. After 1 year, mGFR was not different between groups. No specific adverse events were observed in the bRESCAP group. Urine expression of injury biomarkers CCL14, NGAL and Cystatin C was lower in the bRESCAP group at day seven. This was statistically significant.CONCLUSION: This study illustrates that bRESCAP treatment is feasible in kidney transplantation, might have a dampening effect on IRI induced renal inflammation, and raises no safety concerns. Future research will evaluate the effects of bRESCAP treatment in donation after circulatory death kidney transplantation where IRI is more pronounced.
KW - alkaline phosphatase
KW - bRESCAP
KW - delayed graft function
KW - graft survival
KW - ischaemia–reperfusion injury
KW - living-donor kidney transplantation
KW - pilot
UR - http://www.scopus.com/inward/record.url?scp=85168137125&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/bcp.15871
DO - https://doi.org/10.1111/bcp.15871
M3 - Article
C2 - 37548047
SN - 0306-5251
VL - 89
SP - 3629
EP - 3636
JO - British journal of clinical pharmacology
JF - British journal of clinical pharmacology
IS - 12
ER -