Comparison of acute kidney injury following brain death between male and female rats

Armstrong-Jr, Roberto; Ricardo-da-Silva, Fernanda Yamamoto; Vidal-dos-Santos, Marina; Anunciação, Lucas Ferreira da; Ottens, Petra J.; Correia, Cristiano Jesus; Moreira, Luiz Felipe Pinho; Leuvenink, Hendrik Gerrit Derk; Breithaupt-Faloppa, Ana Cristina

doi:10.1016/j.clinsp.2023.100222

Acessibilidade / Reportar erro

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Original articles • Clinics 78 • 2023 • https://doi.org/10.1016/j.clinsp.2023.100222 copy

Comparison of acute kidney injury following brain death between male and female rats

Authorship SCIMAGO INSTITUTIONS RANKINGS

Highlights

Experimental evidence suggested that hypoperfusion could impact organ viability.
High eNOS-expression in female rats favored the maintenance of renal perfusion.
BD-female rats showed progressive inflammatory responses.

Abstract

Background

Clinical reports associate kidneys from female donors with worse prognostic in male recipients. Brain Death (BD) produces immunological and hemodynamic disorders that affect organ viability. Following BD, female rats are associated with increased renal inflammation interrelated with female sex hormone reduction. Here, the aim was to investigate the effects of sex on BD-induced Acute Kidney Injury (AKI) using an Isolated Perfused rat Kidney (IPK) model.

Methods

Wistar rats, females, and males (8 weeks old), were maintained for 4h after BD. A left nephrectomy was performed and the kidney was preserved in a cold saline solution (30 min). IPK was performed under normothermic temperature (37°C) for 90 min using WME as perfusion solution. AKI was assessed by morphological analyses, staining of complement system components and inflammatory cell markers, perfusion flow, and creatinine clearance.

Results

BD-male kidneys had decreased perfusion flow on IPK, a phenomenon that was not observed in the kidneys of BD-females (p< 0.0001). BD-male kidneys presented greater proximal (p= 0.0311) and distal tubule (p= 0.0029) necrosis. However, BD-female kidneys presented higher expression of eNOS (p= 0.0060) and greater upregulation of inflammatory mediators, iNOS (p= 0.0051), and Caspase-3 (p= 0.0099). In addition, both sexes had increased complement system formation (C5b-9) (p=0.0005), glomerular edema (p= 0.0003), and nNOS (p= 0.0051).

Conclusion

The present data revealed an important sex difference in renal perfusion in the IPK model, evidenced by a pronounced reduction in perfusate flow and low eNOS expression in the BD-male group. Nonetheless, the upregulation of genes related to the proinflammatory cascade suggests a progressive inflammatory process in BD-female kidneys.

Keywords
Brain death; Sex differences; Acute kidney injury; Isolated perfused kidney; Rat

	Renal perfusion
	Male		Female		P Anova
	Non-perfused (RK)	Perfused (LK)	Non-perfused (RK)	Perfused (LK)	P _{Sex × Time}	P _Sex	P _Time
MPO Stained cells/Total area (mm²)	0.042 ± 0.009	0.038 ± 0.020	0.031 ± 0.009	0.034 ± 0.012	0.4754	0.1764	0.9458
ED-1 Stained cells/Total area (mm²)	0.094 ± 0.024	0.141 ± 0.057^a a p< 0.05 in relation to non-perfused kidney.	0.078 ± 0.033	0.090 ± 0.031	0.1435	0.0606	0.0192
C3/C3d Stained area / Total area	0.046 ± 0.008	0.065 ± 0.013^a a p< 0.05 in relation to non-perfused kidney.	0.059 ± 0.010	0.058 ± 0.010	0.0178	0.5368	0.0384
C5b-9 (membrane attack complex) Stained area / Total area	0.013 ± 0.009	0.082 ± 0.047^a a p< 0.05 in relation to non-perfused kidney.	0.016 ± 0.008	0.061 ± 0.035^a a p< 0.05 in relation to non-perfused kidney.	0.3358	0.3691	0.0005

Faculdade de Medicina / USP Rua Dr Ovídio Pires de Campos, 225 - 6 and., 05403-010 São Paulo SP - Brazil, Tel.: (55 11) 2661-6235 - São Paulo - SP - Brazil
E-mail: clinics@hc.fm.usp.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] ⁎ Corresponding author. E-mail address:ana.breithaupt@hc.fm.usp.br (A.C. Breithaupt-Faloppa).