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.

Cardiac transcriptomic changes induced by early CKD in mice reveal novel pathways involved in the pathogenesis of Cardiorenal syndrome type 4

“…However, acute kidney injury secondary to obstructive nephropathy is frequent, impacting the morbidity and mortality of affected patients [ 60 ]. Thus, using UUO models in which the ureteric obstruction is surgically reversed (r-UUO) allows for kidney decompression and urinary flow restoration to the bladder while providing the opportunity to study the resolution of inflammation and tissue repair [ 34 , 61 ]. It is unclear whether removing the harmful stimulus at different times after ureteral obstruction could restore the DEGs in UUO hearts to Sham levels, mainly since there is evidence that relieving the urinary tract cannot fully recover kidney function and has residual impairments that can lead to ESRD [ 14 ].…”

Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry

“…We next defined whether Rac1 played a role in CD repair following injury using a well-established model of reversible UUO (24)(25)(26). In this model, microvascular clamps are used instead of sutures for ureteral ligation allowing for successful decompression and injury recovery (Fig.…”

“…Slices were then washed thoroughly three times in PBS with 2 to 3 hours per washing step. Slices were dehydrated in a methanol series (25,50,75,100, and 100%), 5 min each step, and transferred into BABB solution (benzyl alcohol and benzyl benzoate at a 1:2 ratio) in an Eppendorf tube for 20 min. Once the slices were translucent, they were placed into a glass-bottom dish (MatTek, #P35-1.5-14-C) containing 100 μl of BABB solution for confocal imaging.…”

Animal Models of Kidney Disease: Challenges and Perspectives

“…Contrary to the irreversible model of UUO, reversible UUO model has been established to study the resolution of inflammation and fibrosis by relieving the ligation of the ureter. 56 Epidemiological studies have shown that AKI is a significant risk factor leading to progressive CKD. 57 Consistent with clinical studies, a variety of experimental models have demonstrated that AKI can result in chronic damage and lead to CKD.…”