Abstract
ABSTRACTThe rat has classically been the species of choice for pharmacological studies and disease modeling, providing a source of high-quality physiological data on cardiovascular and renal pathophysiology over many decades. Recent developments in genome engineering now allow us to capitalize on the wealth of knowledge acquired over the last century. Here, we review rat models of hypertension, diabetic nephropathy, and acute and chronic kidney disease. These models have made important contributions to our understanding of renal diseases and have revealed key genes, such as Ace and P2rx7, involved in renal pathogenic processes. By targeting these genes of interest, researchers are gaining a better understanding of the etiology of renal pathologies, with the promised potential of slowing disease progression or even reversing the damage caused. Some, but not all, of these target genes have proved to be of clinical relevance. However, it is now possible to generate more sophisticated and appropriate disease models in the rat, which can recapitulate key aspects of human renal pathology. These advances will ultimately be used to identify new treatments and therapeutic targets of much greater clinical relevance.
Highlights
The prevalence of chronic kidney disease (CKD) is estimated to be 8-16% worldwide (Jha et al, 2013; Stevens et al, 2007)
This study revealed that AngII-receptor blocker (ARB) had an anti-fibrotic effect, independent of hemodynamic effects, in the unilateral ureteral obstruction (UUO) model of rapid renal fibrosis, which induces a marked change in renal perfusion
The potential of bonemarrow-derived mesenchymal stem cells (MSCs) to accelerate healing has been demonstrated in several rat models of hypertension and of renal disease, including in the anti-Thy1.1 model (Li et al, 2006), the 5/6th nephrectomy model of progressive CKD (Cavaglieri et al, 2009; Choi et al, 2009) and in an Acute kidney injury (AKI) model induced by cisplatin (Urt-Filho et al, 2016)
Summary
The prevalence of chronic kidney disease (CKD) is estimated to be 8-16% worldwide (Jha et al, 2013; Stevens et al, 2007). We emphasize the utility and limitations of the rat in recapitulating features of human renal pathologies in vivo and how this model organism has shed light on complex underlying mechanisms of disease progression of therapeutic relevance – information that might lead to the development of new drug treatments and targets (Aitman et al, 2016, 2008).
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