Post-Ischemic Renal Fibrosis Progression Is Halted by Delayed Contralateral Nephrectomy: The Involvement of Macrophage Activation.

Abstract

(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.

• Authors: Pál Tod, Eva Nora Bukosza, Beáta Róka, Tamás Kaucsár, Attila Fintha, Tibor Krenács, Gábor Szénási, Péter Hamar
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 11 (May 28 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32481551 (Publication Type: Journal Article)

Chemical References

• Ccl2 protein, mouse
• Chemokine CCL2
• Lipocalin-2
• Urea

Topics

• Acute Kidney Injury (surgery, therapy)
• Animals
• Blood Urea Nitrogen
• Chemokine CCL2 (metabolism)
• Disease Progression
• Fibrosis (metabolism)
• Inflammation
• Kidney (metabolism, pathology)
• Lipocalin-2 (blood)
• Macrophage Activation
• Macrophages (metabolism)
• Male
• Mice
• Nephrectomy (methods)
• Oxidative Stress
• Renal Insufficiency, Chronic (surgery, therapy)
• Reperfusion Injury (metabolism)
• Translational Research, Biomedical
• Urea (blood)