BACKGROUND: Ischemia/reperfusion (I/R) injury has a major impact on kidney graft function and survival. Animal studies have suggested a role for complement activation in mediating I/R injury; however, results are not unambiguous. Whether complement activation is involved in clinical I/R injury in humans is still unclear. METHODS: In the present study, we assessed the formation and release of C5b-9 during early reperfusion in clinical kidney transplantation in living donor, brain-dead donor, and cardiac dead donor kidney transplantation. By arteriovenous measurements and histologic studies, local terminal complement activation in the reperfused kidney was assessed. RESULTS: There was no release of soluble C5b-9 (sC5b-9) from living donor kidneys, nor was there a release of C5a. In contrast, instantly after reperfusion, there was a significant but transient venous release of sC5b-9 from the reperfused kidney graft in brain-dead donor and cardiac dead donor kidney transplantation. This short-term activation of the terminal complement cascade in deceased-donor kidney transplantation was not reflected by renal tissue deposition of C5b-9 in biopsies taken 45 min after reperfusion. CONCLUSIONS: This systematic study in human kidney transplantation shows an acute but nonsustained sC5b-9 release on reperfusion in deceased-donor kidney transplantation. This instantaneous, intravascular terminal complement activation may be induced by intravascular cellular debris and hypoxic or injured endothelium.
BACKGROUND:Ischemia/reperfusion (I/R) injury has a major impact on kidney graft function and survival. Animal studies have suggested a role for complement activation in mediating I/R injury; however, results are not unambiguous. Whether complement activation is involved in clinical I/R injury in humans is still unclear. METHODS: In the present study, we assessed the formation and release of C5b-9 during early reperfusion in clinical kidney transplantation in living donor, brain-dead donor, and cardiac dead donor kidney transplantation. By arteriovenous measurements and histologic studies, local terminal complement activation in the reperfused kidney was assessed. RESULTS: There was no release of soluble C5b-9 (sC5b-9) from living donor kidneys, nor was there a release of C5a. In contrast, instantly after reperfusion, there was a significant but transient venous release of sC5b-9 from the reperfused kidney graft in brain-dead donor and cardiac dead donor kidney transplantation. This short-term activation of the terminal complement cascade in deceased-donor kidney transplantation was not reflected by renal tissue deposition of C5b-9 in biopsies taken 45 min after reperfusion. CONCLUSIONS: This systematic study in human kidney transplantation shows an acute but nonsustained sC5b-9 release on reperfusion in deceased-donor kidney transplantation. This instantaneous, intravascular terminal complement activation may be induced by intravascular cellular debris and hypoxic or injured endothelium.
Authors: Juan S Danobeitia; Tiffany J Zens; Peter J Chlebeck; Laura J Zitur; Jose A Reyes; Michael J Eerhart; Jennifer Coonen; Saverio Capuano; Anthony M D'Alessandro; Jose R Torrealba; Daniel Burguete; Kevin Brunner; Edwin Van Amersfoort; Yolanda Ponstein; Cees Van Kooten; Ewa Jankowska-Gan; William Burlingham; Jeremy Sullivan; Arjang Djamali; Myron Pozniak; Yucel Yankol; Luis A Fernandez Journal: Am J Transplant Date: 2020-02-20 Impact factor: 8.086
Authors: Bernd Schröppel; Peter S Heeger; Heather Thiessen-Philbrook; Isaac E Hall; Mona D Doshi; Francis L Weng; Peter P Reese; Chirag R Parikh Journal: Transplantation Date: 2019-01 Impact factor: 4.939
Authors: Neetika Garg; Yuzhou Zhang; Anne Nicholson-Weller; Eliyahu V Khankin; Nicolò Ghiringhelli Borsa; Nicole C Meyer; Susan McDermott; Isaac E Stillman; Helmut G Rennke; Richard J Smith; Martha Pavlakis Journal: Nephrol Dial Transplant Date: 2018-12-01 Impact factor: 5.992
Authors: Kirsten A Kortekaas; Dorottya K de Vries; Mark Roest; Marlies Ej Reinders; Eric P van der Veer; Robert Jm Klautz; Philip G de Groot; Alexander F Schaapherder; Jan H Lindeman Journal: Am J Transl Res Date: 2018-03-15 Impact factor: 4.060