A Murine Model of Irreversible and Reversible Unilateral Ureteric Obstruction

Abstract

Obstruction of the kidney may affect native or transplanted kidneys and results in kidney injury and scarring. Presented here is a model of obstructive nephropathy induced by unilateral ureteric obstruction (UUO), which can either be irreversible (UUO) or reversible (R-UUO). In the irreversible UUO model, the ureter may be obstructed for variable periods of time in order to induce increasingly severe renal inflammation and interstitial fibrotic scarring. In the reversible R-UUO model the ureter is obstructed to induce hydronephrosis, tubular dilation and inflammation. After a suitable period of time the ureteric obstruction is then surgically reversed by anastomosis of the severed previously obstructed ureter to the bladder in order to allow complete decompression of the kidney and restoration of urinary flow to the bladder. The irreversible UUO model has been used to investigate various aspects of renal inflammation and scarring including the pathogenesis of disease and the testing of potential anti-inflammatory or anti-fibrotic therapies. The more challenging model of R-UUO has been used by some investigators and does offer significant research potential as it allows the study of inflammatory and immune processes and tissue remodeling in an injured and scarred kidney following the removal of the injurious stimulus. As a result, the R-UUO model offers investigators the opportunity to explore the resolution of kidney inflammation together with key aspects of tissue repair. These experimental models are of relevance to human disease as patients often present with obstruction of the renal tract that requires decompression and are commonly left with significant residual kidney impairment that has no current treatment options and may lead to eventual end stage kidney failure. Video LinkThe video component of this article can be found at

Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease

“…In Cyp1a1mRen2 rats, chronic hyperglycaemia and hypertension induces pro-fibrotic and immune gene expression, whereas subsequent tight glycaemic and blood pressure control down-regulates pro-fibrotic pathways while innate immune genes remain persistently elevated, with evidence of a switch towards a more reparative macrophage phenotype (32,34). In the reversible unilateral ureteric obstruction (R-UUO) model, we (33) and others (35) have demonstrated regression of established tubulointerstitial fibrosis following reversal of obstruction, with partial persistence of interstitial macrophages. However, the macrophage heterogeneity during induction and regression of fibrosis is not yet established.…”

“…In order to dissect the molecular pathways mediating injury and repair in the kidney, we have developed rodent models in which sustained renal injury induces renal fibrosis, but where the injury can be withdrawn to facilitate repair (32,33). In Cyp1a1mRen2 rats, chronic hyperglycaemia and hypertension induces pro-fibrotic and immune gene expression, whereas subsequent tight glycaemic and blood pressure control down-regulates pro-fibrotic pathways while innate immune genes remain persistently elevated, with evidence of a switch towards a more reparative macrophage phenotype (32,34).…”

Does a Ureteral Obstruction Affect the Contralateral Kidney Morphology? A Stereological Analysis in a Rodent Model

“…In the present study, a group of animals submitted to UO was treated with nephrectomy in order to simulate one possible treatment for this condition. A rodent model of reversible unilateral UO was created by the reimplantation of the ureter into the bladder [34, 35]. Although this effectively restores the urine flow, it is still quite different from the normal treatment of UO in most clinical settings.…”

Reversal Unilateral Ureteral Obstruction: A Mice Experimental Model

“…In addition, catheterized individual ureters at the termination of their experiments to measure renal function in postobstructed and contralateral kidneys (used as control), failed in 4 out of 11 cases [20]. Also, another author that performed this model noted the frequent development of a fibrotic ureteric stricture at the site of the clamp after 7 days of UUO [22].…”

“…Only a few models have been able to perform a correct reversibility of the obstruction by anastomosis of the severed previously obstructed ureter to the bladder. However, it requires significant surgical expertise and continues to be less frequently used [21,22].…”