Az orvos-, egészségtudományi- és gyógyszerészképzés tudományos műhelyeinek fejlesztése(EFOP-3.6.3-VEKOP-16-2017-00009)
Támogató: EFOP-VEKOP
(1) Background: Successful treatment of acute kidney injury (AKI)-induced chronic
kidney disease (CKD) is unresolved. We aimed to characterize the time-course of changes
after contralateral nephrectomy (Nx) in a model of unilateral ischemic AKI-induced
CKD with good translational utility. (2) Methods: Severe (30 min) left renal ischemia-reperfusion
injury (IRI) or sham operation (S) was performed in male Naval Medical Research Institute
(NMRI) mice followed by Nx or S one week later. Expression of proinflammatory, oxidative
stress, injury and fibrotic markers was evaluated by RT-qPCR. (3) Results: Upon Nx,
the injured kidney hardly functioned for three days, but it gradually regained function
until day 14 to 21, as demonstrated by the plasma urea. Functional recovery led to
a drastic reduction in inflammatory infiltration by macrophages and by decreases in
macrophage chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-α)
mRNA and most injury markers. However, without Nx, a marked upregulation of proinflammatory
(TNF-α, IL-6, MCP-1 and complement-3 (C3)); oxidative stress (nuclear factor erythroid
2-related factor 2, NRF2) and fibrosis (collagen-1a1 (Col1a1) and fibronectin-1 (FN1))
genes perpetuated, and the injured kidney became completely fibrotic. Contralateral
Nx delayed the development of renal failure up to 20 weeks. (4) Conclusion: Our results
suggest that macrophage activation is involved in postischemic renal fibrosis, and
it is drastically suppressed by contralateral nephrectomy ameliorating progression.
