C1-inhibitor Treatment Decreases Renal Injury in an Established Brain-dead Rat Model

Felix Poppelaars, Neeltina M Jager, Juha Kotimaa, Henri G D Leuvenink, Mohamed R Daha, Cees van Kooten, Marc A Seelen, Jeffrey Damman

OnderzoeksoutputAcademicpeer review

13 Citaten (Scopus)

Samenvatting

BACKGROUND: Kidneys derived from brain-dead (BD) donors have lower graft survival rates compared to kidneys from living donors. Complement activation plays an important role in brain death. The aim of our study was therefore to investigate the effect of C1-inhibitor (C1-INH) on BD-induced renal injury.

METHODS: Brain death was induced in rats by inflating a subdurally placed balloon catheter. Thirty minutes after BD, rats were treated with saline, low-dose or high-dose C1-INH. Sham-operated rats served as controls. After 4 hours of brain death, renal function, injury, inflammation and complement activation was assessed.

RESULTS: High-dose C1-INH treatment of BD donors resulted in significantly lower renal gene expression and serum levels of IL-6. Treatment with C1-INH also improved renal function and reduced renal injury, reflected by the significantly lower KIM-1 gene expression and lower serum levels of LDH and creatinine. Furthermore, C1-INH effectively reduced complement activation by brain death and significantly increased functional levels. However, C1-INH treatment did not prevent renal cellular influx.

CONCLUSIONS: Targeting complement activation after the induction of brain death reduced renal inflammation and improved renal function, before transplantation. Therefore, strategies targeting complement activation in human BD donors might clinically improve donor organ viability and renal allograft survival.

Originele taal-2English
Pagina's (van-tot)79-87
Aantal pagina's9
TijdschriftTransplantation
Volume102
Nummer van het tijdschrift1
Vroegere onlinedatum21-jul-2017
DOI's
StatusPublished - 1-jan-2018

Citeer dit