Reversal Unilateral Ureteral Obstruction: A Mice Experimental Model

Abstract

Background/aims: Reversible unilateral ureteral obstruction (R-UUO) is a model of renal injury used to study the structural and functional recovery of the kidneys after relief of the obstruction. This model has a prominent potential for the study of inflammatory and immune processes, cellular and tissue regeneration. Here we sought to describe a model of renal injury and repair R-UUO in mice.

Methods: Eight week-old C57BL/6J male mice were divided into 5 groups (n = 5 each): UUO day 1, 2, 3, 4 and 5. R-UUO was performed with a microvascular clamp. At day 3, the ureteral clamp was removed and nephrectomy of the contralateral kidney was performed. Mice were sacrificed 48 h afterwards (day 5). An extra group with unilateral nephrectomy without UUO was added. Wild type mice were used as controls. Blood and tissue samples were collected for creatinine, immunohistochemistry and kidney mRNA gene expression analysis.

Results: In the analysis of the obstructed kidney, we observed acute kidney injury with creatinine that doubled its baseline value; histological signs of tubular damage; increased inflammatory response evaluated by F4/80 macrophage; upregulation of pro-inflammatory and pro-fibrotic cytokines such as IL-2, MCP-1, CD40 and TGF-β1 and increased α-smooth muscle actin staining and mild fibrosis. Once the clamp was removed, we observed the amelioration of the kidney function, pathological lesions and the inflammatory response.

Conclusion: This R-UUO model is an easy, reproducible and reliable method to assess kidney recovery after obstructive uropathy. In this setting, the use of this model may help to a better understanding of the process of kidney repair.

Keywords: Obstructive nephropathy; Renal fibrosis; Reversible unilateral ureteral obstruction.