Investigating mechanisms of chronic kidney disease in mouse models

Abstract

Animal models of chronic kidney disease (CKD) are important experimental tools that are used to investigate novel mechanistic pathways and to validate potential new therapeutic interventions prior to pre-clinical testing in humans. Over the past several years, mouse CKD models have been extensively used for these purposes. Despite significant limitations, the model of unilateral ureteral obstruction (UUO) has essentially become the high throughput in vivo model, as it recapitulates the fundamental pathogenetic mechanisms that typify all forms of CKD in a relatively short time span. In addition, several alternative mouse models are available that can be used to validate new mechanistic paradigms and/or novel therapies. Several models are reviewed – both genetic and experimentally induced – that provide investigators with an opportunity to include renal functional study end-points together with quantitative measures of fibrosis severity, something that is not possible with the UUO model.

Characterization of an experimental model of progressive renal disease in rats

“…The development of accurate experimental models for the study of CKD remains a challenge 16 . These models are based on the use of chemical substances [8][9][10] or surgical produres that considerably reduce the renal tissue mass [11][12][13][14][15][16] .…”

“…These models are based on the use of chemical substances [8][9][10] or surgical produres that considerably reduce the renal tissue mass [11][12][13][14][15][16] . The pharmacologic models consist on the use of substance with nephrotoxic potential, which produce injuries to the renal tissue through different molecular mechanisms [8][9][10] .…”

“…These models have the disadvantage that it is not always possible to establish the exact dose to produce a specific degree of renal insufficiency, in addition to the possible occurrence of side effects that may compromise the experimental model. On the other hand, the surgical procedures, characterized by the removal of portions of the renal tissue, have been widely used because they have a high survival rate and a low cost, do not have side effects and can be used to produce progressive levels of renal failure, as shown in this study [11][12][13][14][15][16] .…”

CD39 overexpression does not attenuate renal fibrosis in the unilateral ureteric obstructive model of chronic kidney disease

“…The morbidity and mortality associated with CKD is devastating: individuals with CKD are at high risk for premature death and progression to end stage kidney disease [1,2]. Renal fibrosis is the histological hallmark of CKD and is the final common pathway regardless of the inciting etiology [3]. Renal fibrosis is typified by fibroblast stimulation and collagen deposition.…”

“…The unilateral ureteric obstructive (UUO) model is a highthroughput, reproducible model of renal fibrosis [3]. It is an attractive experimental model because it is species-and strainindependent and demonstrates changes that mimic the pathology of human progressive renal disease.…”