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Room: TBD

P8.072 Sex differences in acute kidney injury following BD - an isolated rat organ perfusion model

Roberto Armstrong Junior, Brazil

1InCor, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil

Abstract

Sex differences in acute kidney injury following BD - an isolated rat organ perfusion model

Roberto Armstrong Junior1,2, Fernanda F Yamamoto Ricardo-Da-Silva1,2, Marina M Vidal-dos-Santos1,2, Petra Ottens2, Cristiano C Jesus Correia1, Luiz Felipe Pinho Moreira1, Henri H Leuvenink2, Ana Cristina AC Breithaupto-Faloppa1.

1InCor, Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP), São Paulo, Brazil; 2University Medical Centre Groningen, Groningen, Netherlands

Introduction: Clinical studies associated female donors’ kidneys with poor outcomes in male recipients. Brain death (BD) leads to hemodynamic and immunologic alterations impacting organ viability. Following BD, female rats present higher renal inflammation correlated to female sex hormones reduction. Here, we aimed to investigate differences between sexes in the renal injury and function triggered by BD using an isolated rat kidney perfusion (IPK) model.

Methods: Female and male Wistar Rats (8 weeks) were preserved following BD for 4h. Sham-operated (S) rats were performed as controls. Left kidneys were collected and maintained in a cold saline solution (30 min). Normothermic IPK (90 min) was performed with Williams Medium E (WME) perfusion fluid. Renal injury and function were estimated by renal morphology analyses, staining of complement system components and inflammatory cell markers, monitoring creatinine clearance, and renal perfusate flow.

Results: BD-female kidneys presented higher eNOS expression (P= 0.0048). Regarding renal flow, BD-males kidneys presented a reduced flow in the IPK (P<0.0001). After IPK, both sexes presented increase in complement system formation/deposition (C5b-9: Pglom=0.0166, Pint<0.0001; C3d: Pglom=0.0008, Pint=0.0105), myeloperoxidase (Pglom=0.0043, Pint<0.0001) and perfusate IL-6 (P=0.0126). Analysis of relative gene expression in perfused kidneys from BD rats revealed a similar upregulation of inflammatory profile in both sexes (IL-1β, IL-6, and eNOS -P<0.0001), however P-selectin (P=0.0001), iNOS (P=0.0002), Caspase-3 (P<0.0001) and BCL-2 (P=0.0153) increased in BD-female kidneys and KIM-1 (P=0.0191) in BD-male kidneys.

Conclusions: Our data showed that despite the inflammatory response similarly found in both sexes, BD leads to renal hypoperfusion in males. The maintenance of perfusion in females seems to be correlated with greater endothelial nitric oxide synthase (eNOS) expression due to high estradiol concentration prior to BD. Once normothermic IPK allows graft assessment and therapeutic drug delivery under physiologic conditions, such findings support further studies emphasizing vascular preservation and anti-inflammatory therapies to order to improve renal graft quality.

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